Cost Effectiveness of Colorectal Cancer Screening Interventions with Their Effects on Health Disparity Being Considered.
The purpose of this study was to evaluate the cost effectiveness of colorectal cancer screening interventions with their effects on health disparity being considered. Markov cohort simulation was conducted with the cycle/duration of 1/40 year(s). Data came from the results of randomized trials and others. Participants were hypothetical cohorts aged 50 years as of year 2013 in 16 Korean provinces. The interventions until the age of 80 were annual organized fecal occult blood test (FOBT) (standard screening), annual FOBT with basic reminders for provinces with higher mortalities than the national average (targeted reminder) and annual FOBT with basic/enhanced reminders for all provinces (universal reminder 1 and 2). The comparison was non-screening, the outcome was quality-adjusted life years, and only medical costs for screening and treatment were considered from a societal perspective. The Atkinson incremental cost effectiveness ratio (Atkinson ICER), the incremental cost effectiveness ratio adjusted by the Atkinson Inequality Index, was used to evaluate the cost effectiveness of the four interventions with their impacts on regional health disparity being considered. Health disparity was smallest (or greatest) in non-screening (or the standard screening). The targeted reminder had smaller health disparity, and smaller Atkinson ICER with respect to standard screening, than did the universal reminder 1 and 2. The targeted reminder might be more cost effective than the universal reminders with their effects on health disparity being considered. This study helps to develop promotional effort for colorectal cancer screening with both the greatest cost effectiveness and the smallest health disparity.


Apoptosis-related factors are relevant to progression of pancreatic neuroendocrine tumors.
Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.


Purple sweet potato pigments scavenge ROS, reduce p53 and modulate Bcl-2/Bax to inhibit irradiation-induced apoptosis in murine thymocytes.
Purple sweet potato (PSP) pigments were proved to protect murine thymocytes from (60)Co γ-ray-induced mitochondria-mediated apoptosis in our previous study. In this study, we further investigated the effect of PSP pigments on apoptosis related ROS, p53 and Bcl-2 family. Cell viability was analyzed by MTT. Apoptosis was certified by DNA ladder detection. Reactive oxygen species (ROS) were detected using 2',7',- dichlorofluorescein diacetate (DCFH-DA) probe. P53, Bcl-2 and Bax proteins were analyzed by western blot. The activities of caspase-3 and caspase-9 were determined by fluorogenic substrates detection. PSP pigments treatment prior to 4Gy (60)Co γ-ray irradiation increased the cell viability and decrease the apoptosis. In the presence of PSP pigments, ROS was scavenged and followed by a p53-depression. A shift in Bcl-2/Bax ratio towards anti-apoptosis was observed as a result of p53-depression. The activities of caspase-9 and caspase-3 were reduced by PSP pigments pretreatment. PSP pigments have a cytoprotective activity against γ radiation. The protective effect of PSP pigments may be involving ROS scavenging, p53 depression and Bcl-2/Bax modulation in a caspase-dependent mitochondrial way.


Antiplatelet and anti-proliferative action of disintegrin from Echis multisquamatis snake venom.
To purify the platelet aggregation inhibitor from Echis multisquamatis snake venom (PAIEM) and characterize its effect on platelet aggregation and HeLa cell proliferation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) were used for PAIEM identification. Platelet aggregation in the presence of PAIEM was studied on aggregometer Solar-AP2110. The changes of shape and granularity of platelets in the presence of PAIEM were studied on flow cytometer COULTER EPICS XL, and degranulation of platelets was estimated using spectrofluorimetry. Indirect enzyme-linked immunosorbent assay was used for the determination of target of PAIEM on platelet surface. An assay based on 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was used to evaluate the effect of PAIEM on the proliferation of HeLa cells in cell culture. The molecular weight of the protein purified from Echis multisquamatis venom was 14.9 kDa. Half-maximal inhibitory concentration (IC50) of PAIEM needed to inhibit adenosine diphosphate (ADP)-induced platelet aggregation was 7 μM. PAIEM did not affect thrombin- or ADP-induced platelet activation, but it did prevent binding of the anti-IIb antibody to glycoprotein IIb/IIIa (GPIIbIIIa)-receptor of adhered platelets and inhibited the viability of HeLa cells by 54%. As a member of the disintegrin family, PAIEM inhibited platelet aggregation and cell proliferation possibly by blocking integrin-mediated interactions. However, it did not impair cellular signaling causing any changes in platelet shape and granularity and did not affect ADP-induced platelet degranulation. This disintegrin was shown to be a potent inhibitor of integrin-mediated cellular interactions including platelet aggregation or cancer cell proliferation.


Covalency in lanthanides. An X-ray absorption spectroscopy and density functional theory study of LnCl6(x-) (x = 3, 2).
Covalency in Ln-Cl bonds of Oh-LnCl6(x-) (x = 3 for Ln = Ce(III), Nd(III), Sm(III), Eu(III), Gd(III); x = 2 for Ln = Ce(IV)) anions has been investigated, primarily using Cl K-edge X-ray absorption spectroscopy (XAS) and time-dependent density functional theory (TDDFT); however, Ce L3,2-edge and M5,4-edge XAS were also used to characterize CeCl6(x-) (x = 2, 3). The M5,4-edge XAS spectra were modeled using configuration interaction calculations. The results were evaluated as a function of (1) the lanthanide (Ln) metal identity, which was varied across the series from Ce to Gd, and (2) the Ln oxidation state (when practical, i.e., formally Ce(III) and Ce(IV)). Pronounced mixing between the Cl 3p- and Ln 5d-orbitals (t2g* and eg*) was observed. Experimental results indicated that Ln 5d-orbital mixing decreased when moving across the lanthanide series. In contrast, oxidizing Ce(III) to Ce(IV) had little effect on Cl 3p and Ce 5d-orbital mixing. For LnCl6(3-) (formally Ln(III)), the 4f-orbitals participated only marginally in covalent bonding, which was consistent with historical descriptions. Surprisingly, there was a marked increase in Cl 3p- and Ce(IV) 4f-orbital mixing (t1u* + t2u*) in CeCl6(2-). This unexpected 4f- and 5d-orbital participation in covalent bonding is presented in the context of recent studies on both tetravalent transition metal and actinide hexahalides, MCl6(2-) (M = Ti, Zr, Hf, U).


Are old running shoes detrimental to your feet? A pedobarographic study.
Footwear characteristics have been implicated in fatigue and foot pain. The recommended time for changing running shoes is every 500 miles. The aim of our study was to assess and compare plantar peak pressures and pressure time integrals in new and old running shoes. This was a prospective study involving 11 healthy female volunteers with no previous foot and ankle problems. New running shoes were provided to the participants. Plantar pressures were measured using the Novel Pedar system while walking with new and participants' personal old running shoes. Plantar pressures were measured in nine areas of the feet. Demographic data, age of old running shoes, Body Mass Index (BMI), peak pressures and pressure-time integral were acquired. The right and left feet were selected at random and assessed separately. Statistical analysis was done using the paired t test to compare measurements between old and new running shoes.The mean peak pressures were higher in new running shoes (330.5 ± 79.6 kiloPascals kPa) when compared to used old running shoes (304 ± 58.1 kPa) (p = 0.01). The pressure-time integral was significantly higher in the new running shoes (110 ± 28.3 kPa s) compared to used old running shoes (100.7 ± 24.0 kPa s) (p = 0.01). Plantar pressure measurements in general were higher in new running shoes. This could be due to the lack of flexibility in new running shoes. The risk of injury to the foot and ankle would appear to be higher if running shoes are changed frequently. We recommend breaking into new running shoes slowly using them for mild physical activity.


Giant Submandibular Calculus Eroding Oral Cavity Mucosa.
Sialolithiasis is the formation of calculi or sialoliths in the salivary gland. It is the most common benign condition of the salivary gland. Sialolithiasis can occur in all salivary glands. The submandibular gland is most commonly affected followed by the parotid gland. Calculi commonly measure less than 10 mm. Calculi of more than 15 mm are termed giant salivary gland calculi and are infrequently reported in the literature. Here, we report a case of unusually large submandibular gland calculus of 5 cm in greatest dimension which caused erosion of the oral cavity.


Socioeconomic Status and Childhood Leukemia Incidence in Switzerland.
Socioeconomic status (SES) discrepancies exist for child and adult cancer morbidity and are a major public health concern. In this Swiss population-based matched case-control study on the etiology of childhood leukemia, we selected the cases from the Swiss Childhood Cancer Registry diagnosed since 1991 and the controls randomly from census. We assigned eight controls per case from the 1990 and 2000 census and matched them by the year of birth and gender. SES information for both cases and controls was obtained from census records by probabilistic record linkage. We investigated the association of SES with childhood leukemia in Switzerland, and explored whether it varied with different definitions of socioeconomic status (parental education, living condition, area-based SES), time period, and age. In conditional logistic regression analyses of 565 leukemia cases and 4433 controls, we found no consistent evidence for an association between SES and childhood leukemia. The odds ratio comparing the highest with the lowest SES category ranged from 0.95 (95% CI: 0.71-1.26; P trend = 0.73) for paternal education to 1.37 (1.00-1.89; P trend = 0.064) for maternal education. No effect modification was found for time period and age at diagnosis. Based on this population-based study, which avoided participation and reporting bias, we assume the potential association of socioeconomic status and childhood leukemia if existing to be small. This study did not find evidence that socioeconomic status, of Switzerland or comparable countries, is a relevant risk factor or strong confounder in etiological investigations on childhood leukemia.


Comparison of central corneal thickness with four different optical devices.
To compare the consistency between the average scores of the contact central corneal thickness measurements from ultrasound pachymetry devices still gold standard, such as iPac® and Echoscan US-500, and noncontact measurements via Pentacam HR and Sirius topography. This prospective study, subsequently admitted to the ophthalmology department, 76 healthy individuals were performed. The measurements were repeated three times for each eye, and average scores were statistically analyzed on the same day and almost at the same time. While measuring the eyes, Pentacam HR, Sirius topography, iPac®, and Echoscan US-500 were used, respectively. The inter-rater agreement of measurements from the devices was assessed with intraclass correlation coefficient, and 95% Confidence Interval and p values demonstrating statistically significance were also presented. In the graphical assessment of the agreement, the Bland-Altman graph was used. Among 76 study participants, 43 (56.6%) were composed of women, and age level was 38.6 ± 12.5 years, ranging between 18 and 69. It was observed that the highest agreement was between the measurements obtained from Echoscan US-500 and iPac® devices, but the agreement between the measurements of different devices was higher than 0.90. Bland-Altman graphics were also investigated; the results of four different devices were seen to be consistent with one another. Therefore, the devices we compared in the study can be used as alternatives to one another due to the higher consistency between CCT measurements provided with through UP devices of Echoscan US-500 and iPac®, and Pentacam HR and Sirius topography devices. 2016/112.


Psychological Impact of Abortion due to Fetal Anomaly: A Review of Published Research.
Over the past several decades, prenatal testing for fetal anomalies has become standard across the developed world. Most women who learn of a severe anomaly during pregnancy elect to terminate. The authors reviewed ten studies which examined the psychological sequelae of pregnant women following prenatal diagnoses of severe life limiting conditions. Based on the available data, the authors found evidence that women who abort due to a poor prenatal diagnosis are at higher risk of post-traumatic stress and depression than women who continue with pregnancy. They also found that current practice is to make reactive recommendations for post-abortion care, suggesting a presumption in favor of abortion, leaving alternatives like perinatal hospice inadequately explored. This review critiques that approach, recommending that doctors and patients need to have the best possible information before a decision is made.


Polydopamine modification of polydimethylsiloxane for multifunctional biomaterials: Immobilization and stability of albumin and fetuin-A on modified surfaces.
The surface of polydimethylsiloxane (PDMS) can be modified to immobilize proteins; however, most existing approaches are limited to complex reactions and achieving multifunctional modifications is challenging. This work applies a simple technique to modify PDMS using polydopamine (PDA) and investigates immobilization of multiple proteins. The surfaces were characterized in detail and stability was assessed, demonstrating that in a buffer solution, PDA modification was maintained without an effect on surface properties. Bovine serum albumin (BSA) and bovine fetuin-A (Fet-A) were used as model biomolecules for simultaneous or sequential immobilization and to understand their use for surface backfilling and functionalization. Based on 125I radiolabeling, amounts of BSA and Fet-A on PDA were determined to be close to double that were obtained on control PDMS surfaces. Following elution with sodium dodecyl sulfate, around 67% of BSA and 63% of Fet-A were retained on the surface. The amount of immobilized protein was influenced by the process (simultaneous or sequential) and surface affinity of the proteins. With simultaneous modification, a balanced level of both proteins could be achieved, whereas with the sequential process, the initially immobilized protein was more strongly attached. After incubation with plasma and fetal bovine serum, the PDA-modified surfaces maintained over 90% of the proteins immobilized. This demonstrates that the biological environments also play an important role in the binding and stability of conjugated proteins. This combination of PDA and surface immobilization methods provides fundamental knowledge for tailoring multifunctional PDMS-based biomaterials with applications in cell-material interactions, biosensing, and medical devices.


Can we buy time? Evaluation of the Swedish government's grant to remediation of contaminated sites.
The major aim of this paper is to analyze how government funding affects the pace of progress in four states of the remediation process of contaminated sites, from basic risk classification to cleanup. We introduce a methodological framework that takes into account the unobserved site-heterogeneity and simultaneously models duration in the different states. The results show that although site-heterogeneity contributes to make remediation a slow process, the third state, from the elaborate risk classification to the cleanup start, is a particular bottleneck. Even if government funding can speed up the process at this state, the effect is minuscule compared to the amounts of funding required. Thus, there is a need for policy to also focus on other barriers to remediation.


Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1.
We are in a crisis of bacterial resistance. For economic reasons, most pharmaceutical companies are abandoning antimicrobial discovery efforts, while, in health care itself, infection control and antibiotic stewardship programs have generally failed to prevent the spread of drug-resistant bacteria. At this point, what can be done? The first step has been taken. Governments and international bodies have declared there is a worldwide crisis in antibiotic drug resistance. As discovery efforts begin anew, what more can be done to protect newly developing agents and improve the use of new drugs to suppress resistance emergence? A neglected path has been the use of recent knowledge regarding antibiotic dosing as single agents and in combination to minimize resistance emergence, while also providing sufficient early bacterial kill. In this review, we look at the data for resistance suppression. Approaches include increasing the intensity of therapy to suppress resistant subpopulations; developing concepts of clinical breakpoints to include issues surrounding suppression of resistance; and paying attention to the duration of therapy, which is another important issue for resistance suppression. New understanding of optimizing combination therapy is of interest for difficult-to-treat pathogens like Pseudomonas aeruginosa, Acinetobacter spp., and multidrug-resistant (MDR) Enterobacteriaceae. These lessons need to be applied to our old drugs to preserve them as well and need to be put into national and international antibiotic resistance strategies. As importantly, from a regulatory perspective, new chemical entities should have a corresponding resistance suppression plan at the time of regulatory review. In this way, we can make the best of our current situation and improve future prospects.


Fulminant Clostridium difficile colitis in a patient with spinal cord injury: case report.
In certain patients with Clostridium difficile colitis (CDC), a life-threatening systemic toxicity may develop despite appropriate and timely medical therapy. Literature search and case report. A 39-year-old man with T10 paraplegia presented with a distended, quiet abdomen following recent treatment with antibiotics for pneumonia. Diarrhea was not present. Complete blood counts demonstrated a marked leukocytosis. A CT scan of the abdomen demonstrated a state of diffuse pancolonic inflammation with peritoneal fluid. The patient was taken to the operating room and underwent total abdominal colectomy with oversewing of the rectal stump and end ileostomy for treatment of the fulminant CDC. Patients with spinal cord injury (SCI) often receive antibiotics for infections of the aerodigestive tree and urinary tract and for problems with skin integrity. A heightened awareness of the development of fulminant CDC remains essential in the care of patients with SCI. Any unexplained abdominal illness after recent antibiotic administration should alert the physician to CDC and its potential as a fulminant, potentially fatal illness.


Kinetics of cytolytic T lymphocyte binding to target cells in suspension.
Cytolytic T lymphocytes (CTL) were able to specifically bind and lyse allogeneic P815 tumor cells and LPS blast cells in suspension. An assay was developed to measure the rate of target cell binding in suspension independent of the rate of lysis. Target cell binding was found to plateau within 3 hr in suspension. The presence of free, functional CTL and targets at these plateaus was demonstrated, indicating that target cell binding was an equilibrium process. Scatchard plots were used to derive values for Kd (apparent affinity) and bmax (maximum binding). Target cell binding in suspension could not be blocked by purified plasma membranes. Target cell binding was compared for CTL generated by secondary in vitro stimulation with intact cells or with purified membranes. These 2 CTL populations yielded distinct values for Kd and bmax. Implications of this kinetic difference for CTL recognition of purified plasma membranes are discussed.


Semi-Automated Visualization and ANalysis of Trends: A "SAVANT" for Facilitating Antimicrobial Stewardship Using Antistaphylococcal Resistance and Consumption as a Prototype.
Governments and health care regulators now require hospitals and nursing homes to establish programs to monitor and report antimicrobial consumption and resistance. However, additional resources were not provided. We sought to develop an approach for monitoring antimicrobial resistance and consumption that health care systems can implement with minimal added costs or modifications to existing diagnostic and informatics infrastructure. Using (1) the electronic laboratory information system of a nationwide managed care network, (2) the 3 most widely used commercial microbiology diagnostic platforms, and (3) Staphylococcus aureus, one of the most common causes of infections worldwide, as a prototype, we validated the approach dubbed "SAVANT" for Semi-Automated Visualization and ANalysis of Trends. SAVANT leverages 3 analytical methods (time series analysis, the autoregressive integrated moving average, and generalized linear regression) on either commercial or open source software to report trends in antistaphylococcal use and resistance. All laboratory results from January 2010 through December 2015 from an annual average of 9.2 million health care beneficiaries were queried. Inpatient and outpatient prescription rates were calculated for 8 key antistaphylococcal compounds. Trends and relationships of antistaphylococcal consumption and resistance among 81 840 unique S. aureus isolates from >6.5 million cultures were revealed. Using existing or freely available resources, SAVANT was successfully implemented across a complex and geographically dispersed 280-hospital network, bridging a critical gap between medical informatics, large-scale data analytics, and mandatory reporting of health care quality metrics.


Two-dimensional blood velocity estimation with ultrasound: speckle tracking versus crossed-beam vector Doppler based on flow simulations in a carotid bifurcation model.
Detailed imaging of complex blood flow may improve early diagnosis of cardiovascular disease. In clinical practice, non-invasive flow imaging has been limited to one-dimensional Doppler techniques. Searching for multi-dimensional estimators, research has given attention to speckle tracking (ST) and vector Doppler (VD). However, these techniques have yet to be validated for complex flow patterns as may arise in diseased arteries. In this work, the properties of ST and crossed-beam VD are compared with a ground truth for clinically relevant flow using an ultrasonic simulation environment coupled with the output from computational fluid dynamics (CFD). The statistical properties (n = 80) of ST and VD were first evaluated for stationary flow in a tube for varying vessel positions and angles, and for varying noise levels. The parameter study demonstrated VD to be a more robust axial velocity estimator, and similar results were obtained overall for the lateral velocity component. As an example, the relative standard deviation was 15% and 8% for ST compared with 3% and 10% for VD, for the axial and lateral velocity component, respectively. Further, performance was evaluated for pulsatile flow conditions in a stenosed carotid bifurcation model. A linear regression analysis showed that both methods overall had a good agreement to the CFD reference, however VD suffered from more spurious artifacts and was severely hampered by aliasing in parts of the cardiac cycle. ST was less accurate in estimating the axial component, but prevailed in estimating velocities well beyond the Nyquist range. Based on our simulations, both methods may be used to image complex flow behavior in the carotid bifurcation, however, considering also the scanning limitations of VD, ST may provide a more consistent and practical approach. Future work will entail in vitro and in vivo validation of these results.


Duodenal Perforation Secondary to Erlotinib Therapy in a Patient With Non-Small Cell Lung Cancer.
Lung cancer is a lethal disease with high mortality, and treatment modality varies with type of tumor and stage of the disease. Targeted molecular therapies have been developed for patients with advanced non-small cell lung cancer. The presence of epidermal growth factor receptor (EGFR) mutation qualifies the patient for EGFR-TKI (tyrosine kinase inhibitor) therapy such as erlotinib, which is not without risk. We report an interesting case of duodenal perforation secondary to erlotinib therapy. This is the second reported case of bowel perforation after erlotinib therapy in a patient with advanced non-small cell lung cancer.


Feed-Forwardness of Spinal Networks in Posture and Locomotion.
We present a new perspective on the concept of feed-forward compared to feedback mechanisms for motor control. We propose that conceptually all sensory information in real time provided to the brain and spinal cord can be viewed as a feed-forward phenomenon. We also propose that the spinal cord continually adapts to a broad array of ongoing sensory information that is used to adjust the probability of making timely and predictable decisions of selected networks that will execute a given response. One interpretation of the term feedback historically entails responses with short delays. We propose that feed-forward mechanisms, however, range in timeframes of milliseconds to an evolutionary perspective, that is, "evolutionary learning." Continuously adapting events enable a high level of automaticity within the sensorimotor networks that mediate "planned" motor tasks. We emphasize that either a very small or a very large proportion of motor responses can be under some level of conscious vs automatic control. Furthermore, we make a case that a major component of automaticity of the neural control of movement in vertebrates is located within spinal cord networks. Even without brain input, the spinal cord routinely uses feed-forward processing of sensory information, particularly proprioceptive and cutaneous, to continuously make fundamental decisions that define motor responses. In effect, these spinal networks may be largely responsible for executing coordinated sensorimotor tasks, even those under normal "conscious" control.


Alcohol and cocaine use prior to suspected suicide: Insights from toxicology.
This study investigates whether there is a relationship between alcohol and cocaine use in deaths where suicide by self-injury is the suspected cause of death. Adults referred by coroners to the Imperial College London Toxicology Unit for toxicological analysis between 2012 and 2016 were reviewed for inclusion criteria. Those who died by self-injury reasoned to be deliberate were included in the analysis. Femoral blood alcohol concentration (BAC) and presence of cocaine or benzoylecognine (a metabolite of cocaine) in blood and/or urine were tabulated and odds ratios calculated. A total of 1722 decedents met inclusion criteria. BAC was ≥50 mg/dL in 29% of decedents. Cocaine was detected in 8.4% of cases. The likelihood of testing positive for cocaine increased with BAC and was most frequent between 100 and 199 mg/dL, consistent with moderate to severe intoxication (odds ratio 5.88, 95% confidence interval 3.80, 9.09; P ≤ 0.001) compared to those with BAC <10 mg/dL. This study demonstrates a correlation between increasing BAC and likelihood of cocaine use prior to suspected suicide, up to a level consistent with severe intoxication. Cocaine use was found in a high proportion of cases relative to the general population reporting regular use. This pattern of drug and alcohol use has previously been given little attention in suicide prevention strategies and clinical prioritisation.


Molecular pathology of non-small cell carcinoma.
Currently, lung cancer is treated by the highest number of therapeutic options and the benefits are based on multiple large-scale sequencing studies, translational research and new drug development, which has promoted our understanding of the molecular pathology of lung cancer. According to the driver alterations, different characteristics have been revealed, such as differences in ethnic prevalence, median age and alteration patterns. Consequently, beyond traditional chemoradiotherapy, molecular-targeted therapy and treatment with immune check-point inhibitors (ICI) also became available major therapeutic options. Interestingly, clinical results suggest that the recently established therapies target distinct lung cancer proportions, particularly between the EGFR/ALK and PD-1/PD-L1-positive subsets, e.g. the kinase inhibitors target driver mutation-positive tumours, whereas driver mutation-negative tumours respond to ICI treatment. These therapeutic efficacy-related differences might be explained by the molecular pathogenesis of lung cancer. Addictive driver mutations promote tumour formation with powerful transformation performance, resulting in a low tumour mutation burden, reduced immune surveillance, and subsequent poor response to ICIs. In contrast, regular tobacco smoke exposure repeatedly injures the proximal airway epithelium, leading to accumulated genetic alterations. In the latter pathway, overgrowth due to alteration and immunological exclusion against neoantigens is initially balanced. However, tumours could be generated from certain clones that outcompete immunological exclusion and outgrow the others. Consequently, this cancer type responds to immune check-point treatment. These pathogenic differences are explained well by the two-compartment model, focusing upon the anatomical and functional composition of distinct cellular components between the terminal respiratory unit and the air-conducting system.


Breeding or assisted reproduction? Relevance of the horse model applied to the conservation of endangered equids.
Many wild equids are at present endangered in the wild. Concurrently, increased mechanization has pushed back the numbers of some old native horse breeds to levels that are no longer compatible with survival of the breed. Strong concerns arose in the last decade to preserve animal biodiversity, including that of rare horse breeds. Genome Resource Banking refers to the cryostorage of genetic material and is an approach for ex situ conservation, which should be applied in combination with in situ conservation programmes. In this review, we propose that, owing to the great reproductive similarity among the different members of the genus Equus, the domestic horse can be used to optimize cryopreservation and embryo production protocols for future application in wild equids. We will give this hypothesis a scientific underpinning by listing successful applications of epididymal sperm freezing, embryo freezing, intracytoplasmic sperm injection, oocyte vitrification and somatic cell nuclear transfer in domestic horses. Some ART fertilization methods may be performed with semen of very low quality or with oocytes obtained after the death of the mare.


Transsulfuration pathway defects and increased glutathione degradation in severe acute pancreatitis.
Glutathione depletion is a consistent feature of the progression of mild to severe acute pancreatitis. In this study, we examined the temporal relationship between cysteine, homocysteine, and cysteinyl-glycine levels; total reduced erythrocyte glutathione; gamma-glutamyl transpeptidase activity; and disease severity. Initially, cysteine concentration was low, at levels similar to those of healthy controls. However, glutathione was reduced whilst cysteinyl glycine and gamma-glutamyl transpeptidase activity were increased in both mild and severe attacks. As the disease progressed, glutathione and cysteinyl glycine were further increased in mild attacks and cysteine levels correlated with homocysteine (r = 0.8, P < 0.001) and gamma-glutamyl transpeptidase activity (r = 0.75, P < 0.001). The progress of severe attacks was associated with glutathione depletion, reduced gamma-glutamyl transpeptidase activity, and increased cysteinyl glycine that correlated with glutathione depletion (r = 0.99, P = 0.01). These results show that glutathione depletion associated with severe acute pancreatitis occurs despite an adequate cysteine supply and could be attributed to heightened oxidative stress coupled to impaired downstream biosynthesis.


Association between diffusivity measures and language and cognitive-control abilities from early toddler's age to childhood.
Extensive improvements in executive functions and language abilities are accompanied by changes in functional connections within the brain and in gray and white matter during the first few years of life. Diffusion tensor imaging provides a unique look into pediatric brain anatomy and critical information regarding white-matter development. The aims of the current study were to investigate the variability in diffusion indices in language and cognitive white-matter tracts, hemispheric lateralization, and how diffusion measures are related to age, language and cognitive abilities from early toddler age to early childhood. Diffusion tensor imaging data were acquired from seventy-four 17-107 month-old typically developing children (mean = 69 months; females = 39). Effects of hemisphere and age on diffusion properties (mean diffusivity, radial diffusivity, axial diffusivity and fractional anisotropy) were measured at 100 points along the length of white-matter tracts related to expressive language and cognitive abilities, including the cingulum bundle, superior longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, arcuate fasciculus and corpus callosum (forceps major and forceps minor). Diffusion properties exhibited variability along the length of the tracts, with hemispheric effect and age differences in specific segments of the tracts. Significant positive correlation was found between fractional anisotropy and expressive language and cognitive abilities. Our results provide a detailed examination of the effect of age and hemisphere on diffusion properties. Furthermore, the results delineate the neural correlates of white-matter microstructure to behavioral language and cognitive performance in white-matter tracts related to language and cognitive abilities at the tract level along with development.


Origin and diversification of a metabolic cycle in oligomer world.
Based on the oligomer-world hypothesis we propose an abstract model where the molecular recognition among oligomers is described in the shape space. The origin of life in the oligomer world is regarded as the establishment of a metabolic cycle in a primitive cell. The cycle is sustained by the molecular recognition. If an original cell acquires the ability of the replication of oligomers, the relationship among oligomers changes due to the poor fidelity of the replication. This change leads to the diversification of metabolic cycles. The selection among diverse cycles is the basis of the evolution. The evolvability is one of the essential characters of life. We demonstrate the origin and diversification of the metabolic cycle by the computer simulation of our model. Such a simulation is expected to be the simplified demonstration of what actually occurred in the primordial soup. Our model describes an analog era preceding the digital era based on the genetic code.


Pumilio2-deficient mice show a predisposition for epilepsy.
Epilepsy is a neurological disease that is caused by abnormal hypersynchronous activities of neuronal ensembles leading to recurrent and spontaneous seizures in human patients. Enhanced neuronal excitability and a high level of synchrony between neurons seem to trigger these spontaneous seizures. The molecular mechanisms, however, regarding the development of neuronal hyperexcitability and maintenance of epilepsy are still poorly understood. Here, we show that pumilio RNA-binding family member 2 (Pumilio2; Pum2) plays a role in the regulation of excitability in hippocampal neurons of weaned and 5-month-old male mice. Almost complete deficiency of Pum2 in adult Pum2 gene-trap mice (Pum2 GT) causes misregulation of genes involved in neuronal excitability control. Interestingly, this finding is accompanied by the development of spontaneous epileptic seizures in Pum2 GT mice. Furthermore, we detect an age-dependent increase in Scn1a (Nav1.1) and Scn8a (Nav1.6) mRNA levels together with a decrease in Scn2a (Nav1.2) transcript levels in weaned Pum2 GT that is absent in older mice. Moreover, field recordings of CA1 pyramidal neurons show a tendency towards a reduced paired-pulse inhibition after stimulation of the Schaffer-collateral-commissural pathway in Pum2 GT mice, indicating a predisposition to the development of spontaneous seizures at later stages. With the onset of spontaneous seizures at the age of 5 months, we detect increased protein levels of Nav1.1 and Nav1.2 as well as decreased protein levels of Nav1.6 in those mice. In addition, GABA receptor subunit alpha-2 (Gabra2) mRNA levels are increased in weaned and adult mice. Furthermore, we observe an enhanced GABRA2 protein level in the dendritic field of the CA1 subregion in the Pum2 GT hippocampus. We conclude that altered expression levels of known epileptic risk factors such as Nav1.1, Nav1.2, Nav1.6 and GABRA2 result in enhanced seizure susceptibility and manifestation of epilepsy in the hippocampus. Thus, our results argue for a role of Pum2 in epileptogenesis and the maintenance of epilepsy.


[Brain physiology and origin of the human subjective experience].
The modern approaches to the problem of the brain basis of subjective experience are reviewed in the paper. The main hypothesis proposes that the events of subjective experience emerge as a result of information comparison and synthesis in crucial for this mental function cortical areas. This synthesis is provided by the special organization of brain processes which includes circulation of nerve impulses in the brain structures. Memory traces are retrieved during this process, and then the appropriate centers of motivations and emotions are activated. Afterwards, the excitation returns to the sites of initial projections, where the synthesis of new information and that retrieved from memory is performed. The hypothesis has been proposed by the author more than twenty years ago and is based on the experimental study of the brain mechanisms of sensation and thinking. It is also shown that the frontal cortex and, particularly, the verbal centers are involved in recognition and decision making. The last part of the paper deals with the problem of the functional significance of subjective events. The possible double bottom-up and top-down determination of brain and mental events is considered and the importance of the search for experimental approaches to these problems is argued.


Dexamethasone promotes von kossa-positive nodule formation and increased alkaline phosphatase activity in costochondral chondrocyte cultures.
This study examined the effect of dexamethasone on von Kossa-positive nodule formation and alkaline phosphate specific activity of costochondral chondrocytes at two distinct stages of maturation. The nodules formed by the more mature growth zone chondrocyte cultures contained von Kossa-positive deposits in the extracellular matrix that had a punctate morphology. The nodules formed by the less mature resting zone cells also contained von Kossa-positive deposits, but differentiation was delayed by three-to-five days compared to the growth zone cell cultures. Dexamethasone stimulated the number of nodules formed and shortened the length of time required for von Kossa-positive nodule formation in both types of cultures. During the first 48 h of exposure to dexamethasone, alkaline phosphatase specific activity in the cell layer of both resting zone and growth zone cultures was increased in a dose-dependent manner. At 12 days post-confluence and thereafter, enzyme activity was inhibited in the dexamethasone-treated cultures. Changes in matrix vesicle alkaline phosphatase specific activity reflected those changes seen in the cell layer after dexamethasone treatment, but with higher magnitude, suggesting that one effect of dexamethasone might be to regulate matrix vesicle function. With the exception of one culture, the chondrocytes did not synthesize type X collagen under any of the experimental conditions used. Fourier transform infrared spectroscopy (FTIR) failed to detect the presence of calcium phosphates in any of the cultures exposed to dexamethasone except one. These results demonstrate that dexamethasone promotes early differentiation events, including nodule formation and increased alkaline phosphatase activity, in costochondral chondrocyte cultures. The failure to detect type X collagen synthesis and mineralization in both dexamamethasone-treated and control cultures suggests that these cultures lack the factors necessary for terminal differentiation and mineralization.


A genome-wide association and gene-environment interaction study for serum triglycerides levels in a healthy Chinese male population.
Triglyceride (TG) is a complex phenotype influenced by both genetic and environmental factors. Recent genome-wide association studies (GWAS) have identified genes or loci affecting lipid levels; however, such studies in Chinese populations are limited. A two-stage GWAS were conducted to identify genetic variants that were associated with TG in a Chinese population of 3495 men. Gene-environment interactions on serum TG levels were further investigated for the seven single nucleotide polymorphisms (SNPs) that were studied in both stages. Two previously reported SNPs (rs651821 in APOA5, rs328 in LPL) were replicated in the second stage, and the combined P-values were 9.19 × 10(-26) and 1.41 × 10(-9) for rs651821 and rs328, respectively. More importantly, a significant interaction between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol consumption on serum TG levels were observed (P = 3.34 × 10(-5)). Rs671 was significantly associated with serum TG levels in drinkers (P = 1.90 × 10(-10)), while no association was observed in non-drinkers (P > 0.05). For drinkers, men carrying the AA/AG genotype have significantly lower serum TG levels, compared with men carrying the GG genotype. For men with the GG genotype, the serum TG levels increased with the quantity of alcohol intake (P = 1.28 × 10(-8) for trend test). We identified a novel, significant interaction effect between alcohol consumption and the ALDH2 rs671 polymorphism on TG levels, which suggests that the effect of alcohol intake on TG occurs in a two-faceted manner. Just one drink can increase TG level in susceptible individuals who carry the GG genotype, while individuals carrying AA/AG genotypes may actually benefit from moderate drinking.


The improvement of ibuprofen dissolution rate through microparticles spray drying processed in an aqueous system.
A study to enhance the dissolution rate of ibuprofen, a poorly water-soluble drug, was carried out through combining specific formulations and processes with the addition of a hydrophilic carrier for the preparation of microparticles. Microparticle production was performed by spray drying ibuprofen microsuspensions formulated in an aqueous system with the addition of ethanol containing Aerosil 200 and Tween 80. We were able to consistently produce microparticles as much as 40% of the dry weight of the input microsuspension. Spray-dried microparticles were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, laser diffractometer mastersizer, and infrared spectroscopy. No modification to the crystalinity and chemical structure of ibuprofen was observed. Dissolution of ibuprofen microparticles reached 100% in 3 minutes compared with less than 10% for unmodified ibuprofen. We concluded that both by the modification of formulation and the spray drying process it is possible to increase the dissolution rate of the tested model drug.


Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration.
Aging is a common risk factor in neurodegenerative disorders. Investigating neuronal aging in an isogenic background stands to facilitate analysis of the interplay between neuronal aging and neurodegeneration. Here we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs) in Huntington's disease identified pathways involving RCAN1, a negative regulator of calcineurin. Notably, RCAN1 protein increased with age in reprogrammed MSNs as well as in human postmortem striatum and RCAN1 knockdown rescued patient-derived MSNs of Huntington's disease from degeneration. RCAN1 knockdown enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, leading to TFEB's nuclear localization by dephosphorylation. Furthermore, G2-115, an analog of glibenclamide with autophagy-enhancing activities, reduced the RCAN1-calcineurin interaction, phenocopying the effect of RCAN1 knockdown. Our results demonstrate that targeting RCAN1 genetically or pharmacologically can increase neuronal resilience in Huntington's disease.


Lack of association between ectoparasite intensities and rabies virus neutralizing antibody seroprevalence in wild big brown bats (Eptesicus fuscus), Fort Collins, Colorado.
Recently, bat ectoparasites have been demonstrated to harbor pathogens of potential importance to humans. We evaluated antirabies antibody seroprevalence and the presence of ectoparasites in big brown bats (Eptesicus fuscus) sampled in 2002 and 2003 in Colorado to investigate if an association existed between ectoparasite intensity and exposure to rabies virus (RV). We used logistic regression and Akaike's Information Criteria adjusted for sample size (AICc) in a post-hoc analysis to investigate the relative importance of three ectoparasite species, as well as bat colony size, year sampled, age class, colony size, and year interaction on the presence of rabies virus neutralizing antibodies (VNA) in serum of wild E. fuscus. We obtained serum samples and ectoparasite counts from big brown bats simultaneously in 2002 and 2003. Although the presence of ectoparasites (Steatonyssus occidentalis and Spinturnix bakeri) were important in elucidating VNA seroprevalence, their intensities were higher in seronegative bats than in seropositive bats, and the presence of a third ectoparasite (Cimex pilosellus) was inconsequential. Colony size and year sampled were the most important variables in these AICc models. These findings suggest that these ectoparasites do not enhance exposure of big brown bats to RV.


Comparative evaluation of three commercial Toxoplasma-specific IgG antibody avidity tests and significance in different clinical settings.
Determination of the avidity of specific IgG antibodies has become a generally accepted diagnostic aid for dating Toxoplasma infection. In this study, the Labsystems, VIDAS and EUROIMMUN Toxoplasma IgG avidity assays were compared on a series of 133 Toxoplasma IgG- and IgM-positive sera from symptomatic patients (n=28), from pregnant (n=43) and non-pregnant (n=26) women, and on 18 IgG-positive and IgM-negative sera from chronically infected patients. The results showed excellent concordance between the Labsystems and VIDAS tests in both the IgM-positive (r=0.82, kappa=0.771) and IgM-negative (kappa=0.609) sera, whilst the agreement of the EUROIMMUN assay with both the Labsystems and VIDAS tests in the IgM-positive sera was moderate (kappa=0.575 and kappa=0.525, respectively) and in the IgM-negative sera was poor (kappa=0.000). Analysis of the kinetics of the maturation of avidity in 13 patients in whom follow-up sera were available showed that, despite a general trend of maturation, in two patients the avidity did not become high during 6 and 11 months of follow-up. In view of the clinical setting, in the symptomatic patients, despite one case of complete discrepancy and five cases of partial discrepancy, the Labsystems and VIDAS tests were in almost perfect agreement (kappa=0.812), whilst the agreement in pregnant and non-pregnant women was substantial (kappa=0.754 and kappa=0.708, respectively). In conclusion, the Labsystems and VIDAS tests are equally reliable for the measurement of Toxoplasma IgG avidity; the choice of test should depend on the laboratory set-up. The EUROIMMUN test may be an acceptable alternative in resource-limited settings, but should be used prudently.


The automatic occluder, a new concept.
An electro-mechanical occluder is described for use in treating problems of binocular vision. A number of methods of achieving the automatic occluder goal are reviewed. Early results of clinical studies now in progress indicate that the "autocluder" has unique clinical usefulness.


Expression of functional major histocompatibility complex class II molecules on HMC-1 human mast cells.
Mast cells hold a key position in the defensive mechanisms against exogenous intruders. In this study, we investigated whether human mast cells express functional major histocompatibility complex (MHC) class II molecules that can transduce endogenous signals and present staphylococcal enterotoxin A (SEA) to T cells. Similar to HMC-1 human mast cell line, umbilical cord blood-derived mast cells express HLA-DR, -DP and -DQ molecules on their surface. MHC class II molecules expressed on HMC-1 cells bind significantly the SEA (a natural MHC class II ligand), and their ligation with specific mAbs or with SEA, leads ultrastructural changes, suggesting their degranulation. Recognition of SEA-bound MHC class II molecules on HMC-1 mast cells by the T cell receptor of K25 cells, an SEA-specific murine T cell hybridoma, triggers significant IL-2 secretion by these T cell hybridomas. Hence, our data point out the expression of functional MHC class II molecules on human mast cells, reinforcing the implication of these cells in the defense mechanisms of acquired immunity.


Effect of ischemic preconditioning on the expression of putative neuroprotective genes in the rat brain.
Previous studies have demonstrated that sublethal ischemic insults protect from subsequent ischemia in the intact brain. There are two windows for the induction of tolerance by ischemic preconditioning (IPC). One occurs within 1 h following IPC, and the other one develops from 1 to 3 days after IPC. The goal of this study was to determine whether IPC neuroprotection may be mediated by expression of known neuroprotective genes and to characterize the temporal and spatial expression patterns of these genes. IPC was produced by bilateral carotid artery occlusions and hypotension (50 mmHg) for 2 min. After various survival times, the expression of MAP-2, brain-derived neurotrophic factor (BDNF), c-jun, c-fos, nerve growth factor (NGF) and HSP70 was assessed by in situ hybridization of coronal brain sections with 35S labeled probes. BDNF, NGF, and c-jun were significantly upregulated in the hippocampus. c-fos was detected in the hippocampus, cortex and striatum. HSP70 mRNA was induced in the cortex, hippocampus, striatum, and thalamus. MAP-2 showed no change in expression, confirming previous studies that no cell death occurs following IPC. The increase in expression of these stress-related, neurotrophic and immediate early genes in response to a mild preconditioning insult may help mediate the protection of vulnerable neurons to subsequent lethal ischemic insults.


Sorafenib induces ferroptosis by promoting TRIM54-mediated FSP1 ubiquitination and degradation in hepatocellular carcinoma.
Ferroptosis is a unique form of regulated cell death that provided a new opportunity for cancer therapy. Ferroptosis suppressor protein 1 (FSP1) is a key regulator in the NAD(P)H/FSP1/CoQ10 antioxidant system, which sever as an oxide redox enzyme to scavenge harmful lipid hydroperoxides and escape from ferroptosis in cells. This study aimed to investigate the role of FSP1 on sorafenib-induced ferroptosis and disclosed the underlying mechanisms. Cell viability, malondialdehyde (MDA), glutathione (GSH), and lipid reactive oxygen species levels were assessed using indicated assay kits. The levels of FSP1 and glutathione peroxidase 4 (GPX4) in the patients with HCC were analyzed based on the database. Western blot and quantitative real-time PCR were performed to detect the protein and mRNA expression. Co-immunoprecipitation was applied to detect the interaction between proteins. Tumor xenograft experiments were used to evaluate whether overexpression of FSP1-inhibited sorafenib-induced ferroptosis in vivo. We verified that sorafenib-induced ferroptosis in HCC. Furthermore, we found that sorafenib decreased the protein level of FSP1, and knockdown FSP1 rendered HCC cells susceptible to sorafenib-induced ferroptosis. Co-immunoprecipitation and ubiquitination assays showed that sorafenib accelerated the TRIM54-mediated FSP1 ubiquitination and degradation. Sorafenib-induced ferroptosis was abrogated by TRIM54 suppression. Mechanically, sorafenib-promoted TRIM54 ubiquitinated and degraded FSP1 by means of the ERK pathway. Moreover, FSP1 enhanced tumor development and decreased HCC cellular susceptibility to sorafenib in vivo. Sorafenib facilitated the TRIM54-mediated FSP1 ubiquitination through the ERK pathway, thereby inducing ferroptosis in HCC cells.


Patient Characteristics and Survival Outcomes of Non-Metastatic, Non-Clear Cell Renal Cell Carcinoma.
Non-clear cell renal cell carcinoma (ccRCC) includes histologically and molecularly distinct subtypes such as papillary, chromophobe, collecting duct, and sarcomatoid RCC, with an incidence ranging from 20% to 25%. Oncologic outcomes and the role of adjuvant systemic therapy [vascular endothelial growth factor inhibitor (VEGFi) or immunotherapy] for non-ccRCC are not well-described. To assess the incidence and survival outcomes of non-ccRCC subtypes in comparison to ccRCC. The National Cancer Database was utilized to identify patients with non-metastatic RCC (T1-T4, N0-N1) between 2004 and 2015. The non-ccRCC cohort was further stratified by histologic subtype: papillary, chromophobe, sarcomatoid, and collecting duct RCC. Multivariable Cox regression models were used to compare overall survival (OS). The 5-year OS for chromophobe, papillary, clear cell, collecting duct, and sarcomatoid RCC was 91%, 82%, 81%, 44%, and 40%, respectively. After adjusting for clinicopathologic and treatment characteristics, there was no significant difference in OS between papillary RCC and ccRCC (p = 0.17). Patients with collecting duct and sarcomatoid subtypes were at over two times increased risk of death compared to patients with clear cell (p < 0.01 and p < 0.01, respectively). Conversely, patients with chromophobe RCC were at 36% decreased risk of death compared to ccRCC (p < 0.01). This hospital-based analysis confirms that collecting duct and sarcomatoid histologic subtypes are uncommon and associated with poor survival after surgery when compared to the other RCC subtypes. Further studies are needed to evaluate the role of neoadjuvant and adjuvant systemic therapies in these subtypes to improve oncologic outcomes.


Phenol-enriched olive oils modify paraoxonase-related variables: A randomized, crossover, controlled trial.
Low paraoxonase (PON)1 activities, and high PON1 and low PON3 protein levels are characteristic of cardiovascular disease. Our aim was to assess short- and long-term effects of virgin olive oils (VOO), enriched with their own phenolic compounds (PC; FVOO) or with them plus complementary PC from thyme (FVOOT), on PON-related variables and the mechanisms involved. Two randomized, controlled, double-blind, and crossover interventions were conducted. In an acute intake study, participants ingested three FVOOs differing in PC content. In a sustained intake study, participants ingested a control VOO and two different FVOOs with the same PC content but differing in PC source. Acute and sustained intake of VOO and FVOO decreased PON1 protein and increased PON1-associated specific activities, while FVOOT yielded opposite results. PON3 protein levels increased only after sustained consumption of VOO. Mechanistic studies performed in rat livers showed that intake of isolated PC from VOO and from thyme modulate mitogen-activated protein kinases and peroxisome proliferator-activated receptors regulating PON synthesis, while a combination of these PCs cancels such regulation. This study reveals that the intake of phenol-enriched FVOOs modulates oxidative balance by modifying PON-related variables according to PC content and source, and this modulation can be perceived as beneficial.


[The combined activities of the temporal cortical area and hippocampus in man during the localization of a moving sound image].
In patients with epileptic lesions in the cortex and mediobasal structures of the brain, studies have been made on the perception of spatial position of sound images during dichotic stimulation. It was established that the extreme interval which is necessary for formation of sensation of the moving sound image increases during right-side lesions of the temporal cortex. During left-side lesion of the temporal lobe, more diffuse disturbances in the trajectory of image movement (from the right and left) are observed, whereas right-side lesions result in disturbances of movement only at the opposite side of the latter. Cortical lesions and those in the mediobasal parts of the temporal lobe are accompanied by identical gradient of disturbances in the trajectory of sound image movement and short-term imprinting of succession of signals which differ with respect to their spatial position. Maximum disturbances are observed during lesions in the cortical and mediobasal parts of the temporal lobe, whereas only cortical lesions or only hippocampal lesions result in less significant disturbances. It is suggested that combined activity of the auditory cortex and hippocamp is necessary for localization of a sound source.


Older people--the reserve army of volunteers?: an analysis of volunteerism among older Australians.
In Australia, as in other Western countries, policy-makers are turning their attention to older people, particularly the early retired, as a rich potential source of volunteers. This study examines volunteer behavior in a sample of older Australians in either their immediate pre or post retirement phase. It involves a secondary analysis of data collected for a study on retirement, and seeks to examine the main social and demographic differences between those who volunteer and those who do not. The key concepts associated with volunteering are the availability of 1) time and 2) social and personal resources. Logistic regression analyses revealed that volunteers are significantly more likely to come from the higher occupational classes, are less likely to be self-employed, and are more likely to view their health positively. Implications of these results for social policy are discussed.


Motility of Mytilus galloprovincialis hemocytes: Sensitivity to paracetamol in vitro exposure.
Pharmaceuticals released into the environment (PiEs) represent an environmental problem of growing concern for the health of ecosystems and humans. An increasing number of studies show that PiEs pose a risk to aquatic organisms. The aim of the present work was to contribute to increasing the knowledge of the effects of PiE on marine biota focusing on the effect of paracetamol on the motility of hemocytes in Mytilus galloprovincialis, a bivalve mollusk species widely utilized as bioindicator organism. Hemocytes are the immunocompetent cells of bivalve mollusks. An early and key stage of mollusk immune response is represented by the recruitment and migration of these cells to the site of infection. Therefore, motility is an intrinsic characteristic of these cells. Here, we first characterized the spontaneous cell movement of M. galloprovincialis hemocytes when plated in a TC-treated polystyrene 96-well microplate. Two different cellular morphotypes were distinguished based on their appearance and motility behavior: spread cells and round-star-shaped cells. The two motility morphotypes were characterized by different velocities as well as movement directness, which were significantly lower in round-star-shaped cells with respect to spread cells. The sensitivity of the motility of M. galloprovincialis hemocytes to paracetamol at different concentrations (0.02, 0.2 and 2 mg/L) was investigated in vitro after 1h and 24h exposure. Paracetamol induced alterations in the motility behavior (both velocity and trajectories) of the hemocytes and the effects were cell-type specific. The study of hemocyte movements at the single cell level by cell tracking and velocimetric parameters analysis provides new sensitive tools for assessing the effects of emerging pollutants at the cellular levels in non-target organisms.


Structures of the intermediates of Kok's photosynthetic water oxidation clock.
Inspired by the period-four oscillation in flash-induced oxygen evolution of photosystem II discovered by Joliot in 1969, Kok performed additional experiments and proposed a five-state kinetic model for photosynthetic oxygen evolution, known as Kok's S-state clock or cycle1,2. The model comprises four (meta)stable intermediates (S0, S1, S2 and S3) and one transient S4 state, which precedes dioxygen formation occurring in a concerted reaction from two water-derived oxygens bound at an oxo-bridged tetra manganese calcium (Mn4CaO5) cluster in the oxygen-evolving complex3-7. This reaction is coupled to the two-step reduction and protonation of the mobile plastoquinone QB at the acceptor side of PSII. Here, using serial femtosecond X-ray crystallography and simultaneous X-ray emission spectroscopy with multi-flash visible laser excitation at room temperature, we visualize all (meta)stable states of Kok's cycle as high-resolution structures (2.04-2.08 Å). In addition, we report structures of two transient states at 150 and 400 µs, revealing notable structural changes including the binding of one additional 'water', Ox, during the S2→S3 state transition. Our results suggest that one water ligand to calcium (W3) is directly involved in substrate delivery. The binding of the additional oxygen Ox in the S3 state between Ca and Mn1 supports O-O bond formation mechanisms involving O5 as one substrate, where Ox is either the other substrate oxygen or is perfectly positioned to refill the O5 position during O2 release. Thus, our results exclude peroxo-bond formation in the S3 state, and the nucleophilic attack of W3 onto W2 is unlikely.


Magnesium Modified β-Tricalcium Phosphate Induces Cell Osteogenic Differentiation In Vitro and Bone Regeneration In Vivo.
In vitro, in vivo, and clinical studies have shown how the physicochemical and biological properties of β-tricalcium phosphate (β-TCP) work in bone regeneration. This study aimed to improve the properties of β-TCP by achieving optimum surface and bulk β-TCP chemical/physical properties through the hydrothermal addition of magnesium (Mg) and to later establish the biocompatibility of β-TCP/Mg for bone grafting and tissue engineering treatments. Multiple in vitro and in vivo analyses were used to complete β-TCP/Mg physicochemical and biological characterization. The addition of MgO brought about a modest rise in the number of β-TCP surface particles, indicating improvements in alkaline phosphatase (ALP) activity on day 21 (p < 0.05) and in the WST-1assay on all days (p < 0.05), with a corresponding increase in the upregulation of ALP and bone sialoprotein. SEM analyses stated that the surfaces of the β-TCP particles were not altered after the addition of Mg. Micro-CT and histomorphometric analysis from rabbit calvaria critical defects resulted in β-TCP/Mg managing to reform more new bone than the control defects and β-TCP control at 2, 6, and 8 weeks (* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, and **** p ≤ 0.0001). The hydrothermal addition of MgO to the β-TCP surfaces ameliorated its biocompatibility without altering its surface roughness resulting from the elemental composition while enhancing cell viability and proliferation, inducing more bone regeneration by osteoconduction in vivo and osteoblastic differentiation in vitro.


[Dynamic electrophysiological examination of heart in patients with sick sinus syndrome in continuous pacing].
Dynamic electrophysiological examination of the heart with allowances for ECG variants of this syndrome and stimulation regimen was performed to predict the results of continuous pacing in patients operated for sick sinus syndrome (SSS). 32 patients had the diagnosis of bradycardia SSS (group 1), 15 patients--bradytachycardia (group 2). 30 patients were on ventricular VVI stimulation, 17 patients--on atrial AAI stimulation. Electrophysiological examination of the heart was performed by means of transesophageal left atrial pacing under programmed, frequent and ultrafrequent stimulation 1, 2, 3 and 4 years after the start of continuous cardiac pacing. In group 2 depression of the sinus function (corrected time of the sinus function recovery, frequency of spontaneous pacemaker, duration of poststimulation pause) under pacing was more distinct than in group 1. Deterioration of atrioventricular conduction was greater in group 1. Three and four years after pacing the Wenckebach point in group 1 lay significantly lower than in group 2. Within the follow-up period 6 (12.8%) patients developed AB-block of the second degree. 4 patients of them were from group 1. Arrhythmogenic atrial readiness depended on the kind of cardiac affection more than on stimulation regimen. Dynamic electrophysiological cardiac examination in the presence of pacing allows following up of natural course of sick sinus syndrome and early correction of the stimulation regimen.


Interleukin-6 expression in disc derangement of human temporomandibular joint and association with osteoarthrosis.
The inflammatory process is a coordinated response that protects host after infection or trauma, involving several molecular reactions. Once the inflammation is closely linked to the process of destruction of the temporomandibular joint, this study aims to examine, by immunohistochemistry, the expression of interleukin-6 (IL-6), an important inflammatory marker, in temporomandibular articular discs of patients with anterior disc displacement with (ADDwR) and without reduction (ADDwoR) and its association with osteoarthrosis (OA). Thirty-eight (n = 38) articular discs were divided into two cutoffs: 1) analysis 1: 4 control (acute pathology), 17 ADDwR, 17 ADDwoR; and 2) analysis 2: without OA (n = 21) and with OA (n = 17). The area of immunostaining was compared statistically between groups (p < 0.05). In the disc samples, no significant differences were observed between the groups ADDwR and ADDwoR, and with and without OA, in respect to the expression of IL-6 by immunohistochemical examination. Future studies should be conducted with a larger sample size, which could clarify the association of the inflammatory mediator IL-6 with temporomandibular joint dysfunction.


Computational neural modeling of speech motor control in childhood apraxia of speech (CAS).
Childhood apraxia of speech (CAS) has been associated with a wide variety of diagnostic descriptions and has been shown to involve different symptoms during successive stages of development. In the present study, the authors attempted to associate the symptoms of CAS in a particular developmental stage with particular information-processing deficits by using computational modeling with the Directions Into Velocities of Articulators (DIVA) model. The hypothesis was that the speech production system in CAS suffers from poor feed-forward control and, consequently, an increased reliance on the feedback control subsystem. In a series of computer simulations, the authors systematically varied the ratio between feed-forward and feedback control during production attempts in the acquisition of feed-forward motor commands. The simulations were evaluated acoustically on 4 selected key symptoms of CAS. Results showed that increasing the reliance on feedback control causes increased severity of these 4 symptoms of CAS: deviant coarticulation, speech sound distortion, searching articulation, and increased variability. The findings support the idea that the key symptoms found in CAS could result from an increased reliance on feedback control due to poor feed-forward commands. Two possible root causes of degraded feed-forward control in CAS are discussed: reduced somatosensory information and increased levels of neural noise.


Endothelium-Specific GTP Cyclohydrolase I Overexpression Restores Endothelial Function in Aged Mice.
This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.


Substrate type and age are risk factors for gastrointestinal parasitism in greyhound kennels.
The control of parasitic infections is particularly challenging in environments that are conducive to the maintenance of parasite lifecycles, such as the greyhound kennel, where the long-term breeding and rearing of dogs is common. The prevalence of gastrointestinal (GI) parasites within the Australian greyhound population has never previously been assessed, which seriously constrains the implementation of effective control measures. The aims of this study were to determine the prevalence and risk factors for GI parasites in Australian greyhounds, identify parasites which may be detrimental to the health and performance of dogs, and evaluate the likelihood of zoonotic transmission to kennel staff. Faecal samples were collected from 721 individual greyhounds situated in kennels across five states of Australia; Western Australia, Queensland, New South Wales, Victoria and Tasmania. Animal husbandry and current parasite control protocols were obtained from each kennel and analysed in conjunction with the detected level of parasitism. Overall parasite prevalence was approximately 60%, ranging from 50 to 70% between states. Eleven parasite genera were identified, with Sarcocystis, hookworm, Giardia and Toxocara detected most frequently. Generalised linear mixed model analyses found the major risk factors associated with parasitism were: a) the type of substrate which dogs were housed; b) age of dogs; and c) geographic region. Parasitism was associated most frequently with young dogs housed on grass/sand substrates, which allowed parasite lifecycles to continue, with constant reinfection the likely outcome. Routine treatment with broad-spectrum anthelmintics did not provide effective control in these environments and the adoption of alternate parasite control strategies is recommended. A substantial risk from zoonotic parasites was also identified, with six of the eleven parasite genera detected considered to be zoonotic and a poor understanding of zoonotic transmission among kennel managers.


TLR4 activation is required for IL-17-induced multiple tissue inflammation and wasting in mice.
IL-17 is a recently identified proinflammatory cytokine that plays pivotal roles in several chronic inflammatory disease models. Its expression was also found to be elevated in the serum of patients with chronic diseases. However, whether elevated systemic IL-17 expression can induce pathophysiological tissue inflammation is unknown. In this study, we demonstrated that systemic overexpression of IL-17 using an adenoviral vector could induce multiple tissue inflammation and wasting in mice. We also found that the expression of TLR4 was increased in tissues of IL-17-overexpressing mice. Moreover, TLR4 activation is required for IL-17-induced tissue inflammation and wasting, as evidenced by the absence of aggressive atrophy in gastrocnemius muscle, neutrophil accumulation, and expression of proinflammatory cytokines downstream of TLR4 in multiple tissues of TLR4-deficient mice. Further investigation revealed that TLR4 endogenous ligands high-mobility group box 1 and heat shock protein 22, were systemically upregulated and might be involved in the IL-17-induced TLR4 activation. Our results suggest that IL-17 may induce disease-associated tissue inflammation and wasting through TLR4 signaling. The study indicates a novel interaction between IL-17 and TLR4 activation and may have implications in the pathogenesis and treatment of chronic diseases.


21 cm cosmology in the 21st century.
Imaging the Universe during the first hundreds of millions of years remains one of the exciting challenges facing modern cosmology. Observations of the redshifted 21 cm line of atomic hydrogen offer the potential of opening a new window into this epoch. This will transform our understanding of the formation of the first stars and galaxies and of the thermal history of the Universe. A new generation of radio telescopes is being constructed for this purpose with the first results starting to trickle in. In this review, we detail the physics that governs the 21 cm signal and describe what might be learnt from upcoming observations. We also generalize our discussion to intensity mapping of other atomic and molecular lines.


Theoretical solution of a spherically isotropic hollow sphere for dynamic thermoelastic problems.
The separation of variables method was successfully used to resolve the spherically symmetric dynamic thermoelastic problem for a spherically isotropic elastic hollow sphere. Use of the integral transform can be avoided by means of this method, which is also appropriate for an arbitrary thickness hollow sphere subjected to arbitrary thermal and mechanical loads. Numerical results are presented to show the dynamic stress responses in the uniformly heated hollow spheres.


How to radiologically identify a spontaneous regression of sporadic vestibular schwannoma?
The natural history of sporadic vestibular schwannoma is unpredictable, with tumors growing, non-growing and even showing spontaneous regression in some rare cases. This retrospective study aims to describe the radiologic signs characterizing and identifying the shrinking vestibular schwannoma. Involution was considered to have occurred if tumor size had decreased by 2 mm or more on its largest diameter. All magnetic resonance imaging scans were reviewed for tumor size, internal auditory meatus size, and tumor characteristics. Volumetric measurements were performed on the first and last scan. Audiometric data were collected at the first and last visit. Fourteen patients with a confirmed spontaneous regression were included, with a mean follow-up of 5 ± 2.6 years. The mean shrinkage rate was 0.9 ± 0.59 mm/year on 2D measurements, and 0.2 ± 0.17 cm3/year on volumetric measurements, with a relative shrinkage of 40 ± 16.9%. Two remarkable radiologic features were observed: First, a festooned aspect, defined by multiple curves in the tumor outline, noticed in 12 cases (86%); second, the appearance of cerebrospinal fluid filling the internal auditory meatus, associated with an enlargement of the internal auditory meatus compared to the contralateral side, and observed in 10 out of 13 cases with internal auditory meatus invasion (77%). Those two aspects were associated in 64% of cases. These two newly reported radiologic features could help neurosurgeons, oto-neurosurgeons and neuroradiologists to identify a spontaneous vestibular schwannoma involution at first visit. This could allow any treatment to be postponed, monitoring to be more widely spaced, and patients to be reassured.


[Vaginal ultrasound in perityphlitic abscess].
A 21 year-old woman presented with an encapsulated mass involving the right ovary, tube and caecum. On transvaginal sonography a 15 mm-target structure was surrounded by irregular, echo-poor formations suggestive of an inflamed appendix and a perityphlitic abscess. Transvaginal sonography is of diagnostic value in differentiating an appendiceal abscess from a right-sided tubo-ovarian abscess.


Fibroblast growth factor receptors-1 and -3 play distinct roles in the regulation of bladder cancer growth and metastasis: implications for therapeutic targeting.
Fibroblast growth factor receptors (FGFRs) are activated by mutation and overexpressed in bladder cancers (BCs), and FGFR inhibitors are currently being evaluated in clinical trials in BC patients. However, BC cells display marked heterogeneity in their responses to FGFR inhibitors, and the biological mechanisms underlying this heterogeneity are not well defined. Here we used a novel inhibitor of FGFRs 1-3 and RNAi to determine the effects of inhibiting FGFR1 or FGFR3 in a panel of human BC cell lines. We observed that FGFR1 was expressed in BC cells that also expressed the "mesenchymal" markers ZEB1 and vimentin, whereas FGFR3 expression was restricted to the E-cadherin- and p63-positive "epithelial" subset. Sensitivity to the growth-inhibitory effects of BGJ-398 was also restricted to the "epithelial" BC cells and it correlated directly with FGFR3 mRNA levels but not with the presence of activating FGFR3 mutations. In contrast, BGJ-398 did not strongly inhibit proliferation but did block invasion in the "mesenchymal" BC cells in vitro. Similarly, BGJ-398 did not inhibit primary tumor growth but blocked the production of circulating tumor cells (CTCs) and the formation of lymph node and distant metastases in mice bearing orthotopically implanted "mesenchymal" UM-UC3 cells. Together, our data demonstrate that FGFR1 and FGFR3 have largely non-overlapping roles in regulating invasion/metastasis and proliferation in distinct "mesenchymal" and "epithelial" subsets of human BC cells. The results suggest that the tumor EMT phenotype will be an important determinant of the biological effects of FGFR inhibitors in patients.


In vitro phosphorylation study of the arc two-component signal transduction system of Escherichia coli.
The ArcB and ArcA proteins constitute a two-component signal transduction system that plays a broad role in transcriptional regulation. Under anoxic or environmentally reducing conditions, the sensor kinase (ArcB) is stimulated to autophosphorylate at the expense of ATP and subsequently transphosphorylates the response regulator (ArcA). ArcB is a complex, membrane-bound protein comprising at least three cytoplasmic domains, an N-terminal transmitter domain with a conserved His292 residue (H1), a central receiver domain with a conserved Asp576 residue (D1), and a C-terminal alternative transmitter domain with a conserved His717 residue (H2). To study the phosphoryl transfer pathways of the Arc system, we prepared the following His-tagged proteins: H1, D1, H2, H1-D1, D1-H2, H1-D1-H2, and ArcA. Incubations of various combinations of Arc proteins with [gamma-32P]ATP indicated that H1, but not D1 or H2, catalyzes autophosphorylation; that H1-P transfers the phosphoryl group to D1 much more rapidly than to ArcA; and that D1 accelerates the transphosphorylation of H2. Finally, ArcA is phosphorylated much more rapidly by H2-P than by H1-P. Available data are consistent with a signal transduction model in which (i) reception of a membrane signal(s) triggers autophosphorylation of H1 at His292, (ii) the phosphoryl group can migrate to D1 at Asp576 and subsequently to H2 at His717, and (iii) ArcA receives the phosphoryl group from either His292 or His717, the relative contribution of which is regulated by cytosolic effectors.


Real-Time Deep Image Retouching Based on Learnt Semantics Dependent Global Transforms.
Although artists' actions in photo retouching appear to be highly nonlinear in nature and very difficult to characterize analytically, we find that the net effects of interactively editing a mundane image to a desired appearance can be modeled, in most cases, by a parametric monotonically non-decreasing global tone mapping function in the luminance axis and by a global affine transform in the chrominance plane that are weighted by saliency. This allows us to simplify the machine learning problem of mimicking artists in photo retouching to constructing a deep artful image transform (DAIT) using convolutional neural networks (CNN). The CNN design of DAIT aims to learn the image-dependent parameters of the luminance tone mapping function and the affine chrominance transform, rather than learning the end-to-end pixel level mapping as in the mainstream methods of image restoration and enhancement. The proposed DAIT approach reduces the computation complexity of the neural network by two orders of magnitude, which also, as a side benefit, improves the robustness and generalization capability at the inference stage. The high throughput and robustness of DAIT lend itself readily to real-time video enhancement as well after a simple temporal processing. Experiments and a Turing-type test are conducted to evaluate the proposed method and its competitors.


Diallylpolysulfides induce growth arrest and apoptosis.
Garlic-derived organo sulphur compounds such as diallylsulfides provide a significant protection against carcinogenesis. Chemically synthesized, and highly pure diallylsulfides with a chain of 1-4 sulphur atoms, as well as a range of control compounds, were employed to investigate the influence of these agents on cell viability, cell cycle arrest and induction of apoptosis in HCT116 human colon cancer cells. Diallyltrisulfide, and even more efficiently diallyltetrasulfide treatment of HCT116 cells led to a reduced cell viability, cell cycle arrest and apoptosis. A similar activity was found for the propyl-analogues, while mono- and disulfides were considerably less active. Initial calculations point toward the ability of tri- and tetrasulfides to form reactive oxygen species (ROS). Here, we found that the induction of apoptosis was indeed dependent on the redox-state of the cell, with anti-oxidants being able to prevent sulfide-induced apoptosis. Furthermore, using HCT116 cells which were either positive or negative for p53 revealed that p53 is clearly dispensable for induction of apoptosis. Growth arrest and induction of apoptosis is associated with a considerable reduction of the level of cdc25C. These results support the therapeutic potential of polysulfides and allow insight into the mechanisms based on the polysulfide biochemistry.


Efficiency of osmotic pipe flows.
We present experiments and theory for flows of sugar or salt solutions in cylindrical tubes with semipermeable walls (hollow fiber membranes) immersed in water, quantifying the strength of the osmotic driving force in relation to the dimensionless parameters that specify the system. The pumping efficiency of these flows is limited by the presence of "unstirred" concentration boundary layers near the tube walls, and our primary aim is to understand and quantify these layers and their effect on the flow. We measure the outlet flow rate Q(out) while varying the inlet flow rate Q(*), concentration c(*), and tube length L, and map out the dependence of the flow rate gain γ=Q(out)/Q(*)-1 on these parameters. A theoretical analysis based on (1) the known velocity field for slow flow in cylindrical porous tubes and (2) a parabolic concentration profile allows us to compute analytically how the flow gain depends on the relative magnitude of radial diffusion and advection as well as the ratio of the osmotic velocity to pumping velocity, in very good agreement with experiments and with no adjustable parameters. Our analysis provides criteria that are useful for optimizing osmotic flow processes in, e.g., water purification devices.


Nutrition and immunity: laboratory and clinical aspects.
It is well known that inappropriate nutrient intake accounts for the maintenance of the immunological equilibrium, in humans and animals. Vitamins, elements, lipids, proteins and nucleic acids play an important role in the regulation of cellular and humoral immune responses since single or multiple deficits of these food components have been shown to cause immune abnormalities. For instance, in the course of protein-calorie malnutrition bacterial and/or viral infections represent the major cause of death. Ageing is characterized by a decline of many immune functions, and this process is called immunosenescence. Here, we report novel findings on the inability of superantigens to activate old CD8+, natural killer and B cells, as an expression of cell amnesia. In the elderly, this lack of activation could lead to lethal effects in the case of severe staphylococcal infections. Quite interestingly, recent findings outlined some similarities between human immune deficiency virus (HIV)-1 infection and ageing in terms of immune changes. The model of HIV-infection may be useful for the interpretation of ageing mechanisms and possible therapeutical interventions. Finally, the role of nutrition in different pathological conditions and the use of medical foods for correcting of immune deficits will be described.


Population differentiation of zander (Sander lucioperca) across native and newly colonized ranges suggests increasing admixture in the course of an invasion.
In addition to ecological factors, evolutionary processes can determine the invasion success of a species. In particular, genetic admixture has the potential to induce rapid evolutionary change, which can result from natural or human-assisted secondary contact between differentiated populations. We studied the recent range expansion of zander in Germany focusing on the interplay between invasion and genetic admixture. Historically, the rivers Elbe and Danube harboured the most north-western source populations from which a north-westward range expansion occurred. This was initiated by introducing zander outside its native range into rivers and lakes, and was fostered by migration through artificial canals and stocking from various sources. We analysed zander populations of the native and invaded ranges using nuclear and mitochondrial genetic markers. Three genetic lineages were identified, which were traced to ancestral ranges. Increased genetic diversity and admixture in the invaded region highlighted asymmetric gene flow towards this area. We suppose that the adaptive potential of the invading populations was promoted by genetic admixture, whereas competitive exclusion in the native areas provided a buffer against introgression by novel genotypes. These explanations would be in line with evidence that hybridization can drive evolutionary change under conditions when new niches can be exploited.


[Diagnosis and treatment of cancer of the pancreas].
The article analyzes diagnostics and treatment of 281 patients. The IV degree of the disease was diagnosed in 81 patients (29.2%) and in 102 patients more (33%) it was diagnosed in laparotomy. Palliative operations were performed on 55 patients (19.2%). A conclusion is made that oncological watchfulness of physicians must be higher since the present day methods of diagnostics allow to make diagnosis at any stage of the disease. Lethality after radical operations modified by the author was not more than 15%.


[Confrontation of the radiographic preoperative planning with the postoperative data for uncemented total hip arthroplasty].
For hip prosthesis surgery, the challenge is to obtain optimal function of the instrumented hip but also to eliminate any limb length discrepancy, correct the femur offset and guarantee the center of rotation of the hip joint. Preoperative planning for total hip arthroplasty (THA) enables determination of the appropriate length for the prosthetic neck and the size and eventually the type of implants to use. From a prospective series of 86 patients who underwent first-intention THA for implantation of a noncemented prosthesis, we studied the precision of the outcome as function of the preoperative planning. We also ascertained whether the preoperative planning was sufficient to provide the measurements necessary for correct implant position. We analyzed a prospective series of patients who underwent first-intention THA from January 2004 through January 2006. To be eligible for inclusion, patients could not have a THA of the contralateral hip. The series was composed of 58 females and 28 males, mean age 70.2 years (range 45-93). The reasons for THA were primary degenerative disease (n=76) and aseptic osteonecrosis (n=10). The contalateral hip was intact and free of osteoarthritis with an anatomic presentation considered to be normal. The standard X-ray protocol included an anteroposterior view of the pelvis in the upright position and 10 degrees internal rotation obtained preoperatively and three months postoperatively. All radiographic measurements were made by the same investigator using a manual nondigitalized technique. We compared planning parameters (pivot size and type, length of the neck, and size of the cup) with the final outcome in order to determine the compliance with the preoperative planning. All operations were performed in the lateral supine position under general anesthesia and by the same surgeon. The posterolateral Moore approach was used. All implants were press fit without cement, both for the cup and for the femoral piece. All planning parameters selected for study (offset, size of the head and the cup, length of the neck) were available for 32 hips, giving an overall conformity of 37%. The length of the neck was as planned in 75% of hips, the size of the cup in 62% and the size of the femoral stem in 64%. The offset defined preoperatively was never changed during the operation. Ideal implantation (+/- 5mm for all criteria selected for study) was obtained in 60% of hips; the height of the center of rotation was reproduced in 81% and the lateralization in 84%. Femur lateralization was reproduced in 75% of the hips and hip offset in 66%. Leg length discrepancy was avoided in 85% of the patients. Preoperative planning reliably predicts the final offset of the implanted femoral stem. It is more difficult to predict the size of a press fit cup but in our experience the difference does not greatly affect restitution of the hip anatomy. We readily changed the length of the neck during the operation if necessary and have found that the leg length has been better with this approach. This leads to the observation that all of the planning parameters are not fully accurate because of the magnification effect, anatomic conditions, or possible defective execution. While the overall rate of conformity was low, looking at the results for each element separately provided a useful element for each phase of the operation. We recommend planning a medium length neck so it can be easily changed during the operation. The availability of offset measurements is particularly important to control hip lateralization and leg length. Current advances in computer-assisted surgery should be helpful in improving the imperfections of preoperative planning.


Learning style preferences of first-year dental students at King Saud University in Riyadh, Saudi Arabia: influence of gender and GPA.
The aim of this study was to investigate the learning style preferences of a group of first-year dental students and their relation to gender and past academic performance. A total of 113 first-year dental students (forty-two female, seventy-one male) at King Saud University in Riyadh, Saudi Arabia, participated. The Visual, Aural, Read-write, and Kinesthetic (VARK) questionnaire was used to determine the students' preferred mode of learning. This sixteen-item questionnaire defines preference of learning based on the sensory modalities: visual, aural, reading/writing, and kinesthetic. More than half (59 percent) of the students were found to have multimodal learning preferences. The most common single learning preferences were aural (20 percent) followed by kinesthetic (15.2 percent). Gender differences were not statistically significant. However, a statistically significant difference was found in the mean values of GPA in relation to the students' learning style preferences (p=0.019). Students with a single learning style preference had a lower mean GPA than those with multiple (quad-modal) learning style preferences. For effective instruction, dental educators need to broaden their range of presentation styles to help create more positive and effective learning environments for all students.


Dual-energy digital mammography utilizing stimulated phosphor computed radiography.
Dual-energy subtraction is a radiographic technique for the acquisition of a material selective image by the weighted subtraction of low- and high-energy digital X-ray images. This is achieved by exploiting the energy dependence of the X-ray attenuation components in the image. This can allow the removal of background morphology to enhance the presentation of otherwise obscured details. The detection of microcalcifications in a mammogram by dual-energy techniques has previously been investigated. These investigations indicated that, using dual-energy techniques, small microcalcifications could be extracted from the background breast morphology with sufficient signal to noise ratio (SNR) to be full visualized. The authors present the extension of a theoretical dual-energy model to incorporate practical considerations and then compare the results with experimentally derived data using a commercially available computed radiography system. In particular the extended model now takes into account the energy dependent detective quantum efficiency of a system. This is thought to be a major factor in reducing the efficiency of dual-energy mammography. The theoretical model predicts that dual-exposure dual-energy mammography, utilizing HRIII image plates, could not provide a detail SNR of five for calcifications smaller than 470 mu m. The experimental results verify this and indicate that dual-energy subtraction mammography, utilizing computed radiography, is currently not a viable technique for the detection of clinically significant microcalcifications. Further advances in X-ray image detector efficiency will be required if the full potential of this technique is to be achieved.


Organochlorine pesticides accumulation and breast cancer: A hospital-based case-control study.
The aim of this study is to detect the accumulation status of organochlorine pesticides in breast cancer patients and to explore the relationship between organochlorine pesticides contamination and breast cancer development. We conducted a hospital-based case-control study in 56 patients with breast cancer and 46 patients with benign breast disease. We detected the accumulation level of several organochlorine pesticides products (β-hexachlorocyclohexane, γ-hexachlorocyclohexane, polychlorinated biphenyls-28, polychlorinated biphenyls-52, pentachlorothioanisole, and pp'-dichlorodiphenyldichloroethane) in breast adipose tissues of all 102 patients using gas chromatography. Thereafter, we examined the expression status of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 (HER2), and Ki-67 in 56 breast cancer cases by immunohistochemistry. In addition, we analyzed the risk of breast cancer in those patients with organochlorine pesticides contamination using a logistic regression model. Our data showed that breast cancer patients suffered high accumulation levels of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52. However, the concentrations of pp'-dichlorodiphenyldichloroethane and polychlorinated biphenyls-52 were not related to clinicopathologic parameters of breast cancer. Further logistic regression analysis showed polychlorinated biphenyls-52 and pp'-dichlorodiphenyldichloroethane were risk factors for breast cancer. Our results provide new evidence on etiology of breast cancer.