Older patients' unexpressed concerns about orthopaedic surgery.
As the U.S. population ages, orthopaedic surgeons will increasingly be required to counsel older patients about major surgical procedures. Understanding patient concerns or worries about surgery could help orthopaedic surgeons to assist their patients in making these decisions. The objectives of this study were to explore the nature of patient concerns regarding orthopaedic surgery and to describe how patients raise concerns during visits with orthopaedic surgeons and how orthopaedic surgeons respond. As part of a study involving audiotaping of 886 visits between patients and orthopaedic surgeons, fifty-nine patients sixty years of age or older who were considering surgery were recruited to participate in semistructured telephone interviews at five to seven days and one month after the visit. Patients were asked about their perceptions of the visit and how they made their decision about surgery. These interviews were analyzed to identify patients' concerns with the use of qualitative content analysis and then compared with the audiotaped visits to determine whether these concerns were actually raised during the visit and, if so, how well the orthopaedic surgeons responded. Analyses based on patient race (black or white) were also performed. One hundred and sixty-four concerns pertaining to (1) the surgery (anticipated quality of life after the surgery, the care facility, the timing of the operation, and the patient's capacity to meet the demands of the surgery) and (2) the surgeons (their competency, communication, and professional practices) were identified. Patients raised only 53% of their concerns with the orthopaedic surgeons and were selective in what they disclosed; concerns about the timing of the operation and about the care facility were frequently raised, but concerns about their capacity to meet the demands of the surgery and about the orthopaedic surgeons were not. Orthopaedic surgeons responded positively to 66% of the concerns raised by the patients. Only two concerns were raised in response to direct surgeon inquiry. Patients raised only half their concerns regarding surgery with orthopaedic surgeons. Orthopaedic surgeons are encouraged to fully address how patients' capacity to meet the demands of the surgery, defined by their resources (such as social support, transportation, and finances) and obligations (to family members, employers, and religion), may impinge on their willingness to accept recommended surgery.


Clinical significance and limitations of repeat resection for pediatric malignant neuroepithelial tumors: clinical article.
Maximized tumor resection and minimized surgical morbidity are extremely important in the treatment of children with malignant neuroepithelial tumors. However, the indications for repeat surgery for these tumors remain unclear. The present study investigated the clinical significance and limitations of repeat resection for these tumors. This study included 61 consecutive pediatric patients with malignant neuroepithelial tumor, histologically diagnosed as WHO Grades III and IV. All patients were initially treated between January 1997 and March 2011 and had follow-up of more than 2 years. The number of surgeries, presence of leptomeningeal dissemination, survival, WHO grade, and Eastern Cooperative Oncology Group performance status before and after surgery were retrospectively reviewed. Repeat resections were performed for 21 patients (34.4%). Eastern Cooperative Oncology Group performance status was not aggravated by surgery, even after multiple operations. The 5-year survival rates of patients who received single and repeat surgery were 58.6% and 38.7%, respectively (p = 0.12). The mean interval between initial surgery and leptomeningeal dissemination detection was 331 ± 108 days in the single-surgery group and 549 ± 122 days in the repeat-surgery group (p = 0.19). The median survival time after leptomeningeal dissemination was 580 days in the single-surgery group and 890 days in the repeat-surgery group (p = 0.74). Repeat resection with minimized surgical morbidity is an effective method to achieve better local control of pediatric malignant neuroepithelial tumors. Leptomeningeal dissemination was a leading cause of death, but repeat surgery did not increase the frequency of death.


Trends in storage of digital data.
Trends in the price and performance of several storage technologies are presented with emphasis on magnetic recording and semiconductor memories. Since these technologies present a moving target, new contenders cannot enter the marketplace unless they provide a significant advantage over the entrenched competition. It is concluded that in the next decade, optical storage of digital data can make an impact at the high capacity end-trillion bits and above-provided prices are at least an order of magnitude lower and access at least an order of magnitude faster than in present day systems.


The posterior sacral foramina: an anatomical study.
The vascular and nervous structures and their relations with the spinal nerve roots were examined in the 2nd, 3rd and 4th posterior sacral foramina in relation to percutaneous needle insertion for neuromodulation. A foraminal branch provided by the lateral sacral artery to each foramen entered the inferior lateral quadrant of each foramen, adjacent to the nerve root medially. Facing the posterior sacral aperture and around the sacral nerves, there was no venous plexus. A venous plexus was sometimes present near the median line, and always around the proximal part of the spinal ganglion. The sacral nerve roots, especially the 3rd, had a long extradural course in the foramen, presenting a potential risk of nerve lesions during procedures involving needle insertion.


A systematic review of persuasive marketing techniques to promote food to children on television.
The ubiquitous marketing of energy-dense, nutrient-poor food and beverages is a key modifiable influence on childhood dietary patterns and obesity. Much of the research on television food advertising is focused on identifying and quantifying unhealthy food marketing with comparatively few studies examining persuasive marketing techniques to promote unhealthy food to children. This review identifies the most frequently documented persuasive marketing techniques to promote food to children via television. A systematic search of eight online databases using key search terms identified 267 unique articles. Thirty-eight articles met the inclusion criteria. A narrative synthesis of the reviewed studies revealed the most commonly reported persuasive techniques used on television to promote food to children. These were the use of premium offers, promotional characters, nutrition and health-related claims, the theme of taste, and the emotional appeal of fun. Identifying and documenting these commonly reported persuasive marketing techniques to promote food to children on television is critical for the monitoring and evaluation of advertising codes and industry pledges and the development of further regulation in this area. This has a strong potential to curbing the international obesity epidemic besieging children throughout the world.


Changes in an Enzyme Ensemble During Catalysis Observed by High Resolution XFEL Crystallography.
Enzymes populate ensembles of structures with intrinsically different catalytic proficiencies that are difficult to experimentally characterize. We use time-resolved mix-and-inject serial crystallography (MISC) at an X-ray free electron laser (XFEL) to observe catalysis in a designed mutant (G150T) isocyanide hydratase (ICH) enzyme that enhances sampling of important minor conformations. The active site exists in a mixture of conformations and formation of the thioimidate catalytic intermediate selects for catalytically competent substates. A prior proposal for active site cysteine charge-coupled conformational changes in ICH is validated by determining structures of the enzyme over a range of pH values. A combination of large molecular dynamics simulations of the enzyme in crystallo and time-resolved electron density maps shows that ionization of the general acid Asp17 during catalysis causes additional conformational changes that propagate across the dimer interface, connecting the two active sites. These ionization-linked changes in the ICH conformational ensemble permit water to enter the active site in a location that is poised for intermediate hydrolysis. ICH exhibits a tight coupling between ionization of active site residues and catalysis-activated protein motions, exemplifying a mechanism of electrostatic control of enzyme dynamics.


Learning sensor-based navigation of a real mobile robot in unknown worlds.
In this paper, we address the problem of navigating an autonomous mobile robot in an unknown indoor environment. The parti-game multiresolution learning approach is applied for simultaneous and cooperative construction of a world model, and learning to navigate through an obstacle-free path from a starting position to a known goal region. The paper introduces a new approach, based on the application of the fuzzy ART neural architecture, for on-line map building from actual sensor data. This method is then integrated, as a complement, on the parti-game world model, allowing the system to make a more efficient use of collected sensor information. Then, a predictive on-line trajectory filtering method, is introduced in the learning approach. Instead of having a mechanical device moving to search the world, the idea is to have the system analyzing trajectories in a predictive mode, by taking advantage of the improved world model. The real robot will only move to try trajectories that have been predicted to be successful, allowing lower exploration costs. This results in an overall improved new method for goal-oriented navigation. It is assumed that the robot knows its own current world location-a simple dead-reckoning method is used for localization in our experiments. It is also assumed that the robot is able to perform sensor-based obstacle detection (not avoidance) and straight-line motions. Results of experiments with a real Nomad 200 mobile robot are presented, demonstrating the effectiveness of the discussed methods.


Nanoparticle-based drug delivery via RBC-hitchhiking for the inhibition of lung metastases growth.
Delivery of particle-based theranostic agents via their transportation on the surfaces of red blood cells, commonly referred to as RBC-hitchhiking, has historically been developed as a promising strategy for increasing the extremely poor blood circulation lifetime, primarily, of the large-sized sub-micron agents. Here, we show for the first time that RBC-hitchhiking can be extremely efficient for nanoparticle delivery and tumor treatment even in those cases when no circulation prolongation is observed. Specifically, we demonstrate that RBC-hitchhiking of certain small 100 nm particles, unlike that of the conventional sub-micron ones, can boost the delivery of non-targeted particles to lungs up to a record high value of 120-fold (and up to 40% of the injected dose). To achieve this remarkable result, we screened sub-200 nm nanoparticles of different sizes, polymer coatings and ζ-potentials and identified particles with the optimal RBC adsorption/desorption behavior. Furthermore, we demonstrated that such RBC-mediated rerouting of particles to lungs can be used to fight pulmonary metastases of aggressive melanoma B16-F1. Our findings could change the general paradigm of drug delivery for cancer treatment with RBC-hitchhiking. It is not the blood circulation lifetime that is the key factor for nanoparticle efficiency, but rather the complexation of nanoparticles with the RBC. The demonstrated technology could become a valuable tool for development of new strategies based on small nanoparticles for the treatment of aggressive and small-cell types of cancer as well as other lung diseases.


International use of health status questionnaires in Parkinson's disease: translation is not enough.
The present study assessed the linguistic and content validity of the Swedish version of the 39-item Parkinson's disease questionnaire (PDQ-39). The frame question, response alternatives and two of the 39 items yielded substantial linguistic and stylistic problems. Such shortcomings would be expected to influence responses to, and the quality of, the whole questionnaire. Data support content validity of the PDQ-39 as a functional health status questionnaire, although some shortcomings were identified. This preliminary study illustrates the need for documented linguistic validity before new language adaptations of patient-reported outcome measures can be considered suitable for use in clinical trials, research, and practice.


[Determination of avermectin and ivermectin in swine muscular tissues using high performance liquid chromatography-tandem mass spectrometry].
To develop a method for simultaneous determination of avermectin (AVM) and ivermectin (IVM) in swine muscular tissues using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The AVM and IVM were extracted with acetonitrile, cleaned with basic alumina solid phase extraction cartridges, separated through C8 column, and then detected by mass spectrometry in positive ion mode with multiple reaction monitoring (MRM) using an electrospray ionization interface, with quantitative ion pair of 890.4/305.3 and 892.5/307.3 for AVM and IVM, respectively. The linear ranges for both AVM and IVM were between 5 microg/L and 100 microg/L, with a correlation coefficient of 0.9999. The detection limit was 2.0 microg/kg. The recoveries at the spiked concentration of 2 microg/kg, 10 microg/kg and 20 microg/kg ranged from 77.4% to 83.1% for AVM and 77.2% to 84.8% for IVM, with relative standard deviation (RSD) ranging from 8.7% to 11.7% for AVM and 6.3% to 10.3% for IVM, respectively. No AVM and IVM residues were detected in samples taken from Chengdu markets. A HPLC-MS/MS method was successfully developed for determining AVM and IVM in swine muscular tissues, which is simple, sensitive and precise and can meet both domestic and international requirements.


Overreliance on symptom quality in diagnosing dizziness: results of a multicenter survey of emergency physicians.
To assess emergency physicians' diagnostic approach to the patient with dizziness, using a multicenter quantitative survey. We anonymously surveyed attending and resident emergency physicians at 17 academic-affiliated emergency departments with an Internet-based survey (September 1, 2006, to November 3, 2006). The survey respondents ranked the relative importance of symptom quality, timing, triggers, and associated symptoms and indicated their agreement with 20 statements about diagnostic assessment of dizziness (Likert scale). We used logistic regression to assess the impact of "symptom quality ranked first" on odds of agreement with diagnostic statements; we then stratified responses by academic rank. Of the 505 individuals surveyed, 415 responded for an overall response rate of 82%. A total of 93% (95% confidence interval [CI], 90%-95%) agreed that determining type of dizziness is very important, and 64% (95% CI, 60%-69%) ranked symptom quality as the most important diagnostic feature. In a multivariate model, those ranking quality first (particularly resident physicians) more often reported high-risk reasoning that might predispose patients to misdiagnosis (eg, in a patient with persistent, continuous dizziness, who could have a cerebellar stroke, resident physicians reported feeling reassured that a normal head computed tomogram indicates that the patient can safely go home) (odds ratio, 6.74; 95% CI, 2.05-22.19). Physicians report taking a quality-of-symptoms approach to the diagnosis of dizziness in patients in the emergency department. Those relying heavily on this approach may be predisposed to high-risk downstream diagnostic reasoning. Other clinical features (eg, timing, triggers, associated symptoms) appear relatively undervalued. Educational initiatives merit consideration.


Show, Match and Segment: Joint Weakly Supervised Learning of Semantic Matching and Object Co-Segmentation.
We present an approach for jointly matching and segmenting object instances of the same category within a collection of images. In contrast to existing algorithms that tackle the tasks of semantic matching and object co-segmentation in isolation, our method exploits the complementary nature of the two tasks. The key insights of our method are two-fold. First, the estimated dense correspondence fields from semantic matching provide supervision for object co-segmentation by enforcing consistency between the predicted masks from a pair of images. Second, the predicted object masks from object co-segmentation in turn allow us to reduce the adverse effects due to background clutters for improving semantic matching. Our model is end-to-end trainable and does not require supervision from manually annotated correspondences and object masks. We validate the efficacy of our approach on five benchmark datasets: TSS, Internet, PF-PASCAL, PF-WILLOW, and SPair-71k, and show that our algorithm performs favorably against the state-of-the-art methods on both semantic matching and object co-segmentation tasks.


An Overview and Proposed Research Framework for Studying Co-Occurring Mental- and Physical-Health Dysfunction.
Mental- and physical-health conditions co-occur at a rate much higher than chance. Of patients who have a mental-health condition, more than half also have a physical disease, and these cases are associated with increased human suffering and societal cost. Comorbidity research to date has focused on co-occurring mental- and physical-health disorders separately, and relatively little research has examined the co-occurrence of mental- and physical-health dysfunction. In addition, even less is known about why mental- and physical-health dysfunction co-occurs or how to treat these cases. Thus, the aims of this article are to highlight the need for research at the intersection of physical- and mental-health dysfunction and to provide guidance on how to research cases of comorbidity. Toward these ends, we begin by presenting a selective overview of the possible role of biological processes in the co-occurrence of physical- and mental-health dysfunction using specific illustrative examples. Specifically, we outline how biological processes within the immune system and gastrointestinal system could underlie depression, irritable bowel syndrome, and their co-occurrence. We then advance and discuss a proposed research framework, including methodological and analytic guidance, that researchers could use when studying the phenomenon of co-occurring physical- and mental-health dysfunction.


Hysteresis-free nanoplasmonic Pd-Au alloy hydrogen sensors.
The recent market introduction of hydrogen fuel cell cars and the prospect of a hydrogen economy have drastically accelerated the need for safe and accurate detection of hydrogen. In this Letter, we investigate the use of arrays of nanofabricated Pd-Au alloy nanoparticles as plasmonic optical hydrogen sensors. By increasing the amount of Au in the alloy nanoparticles up to 25 atom %, we are able to suppress the hysteresis between hydrogen absorption and desorption, thereby increasing the sensor accuracy to below 5% throughout the investigated 1 mbar to 1 bar hydrogen pressure range. Furthermore, we observe an 8-fold absolute sensitivity enhancement at low hydrogen pressures compared to sensors made of pure Pd, and an improved sensor response time to below one second within the 0-40 mbar pressure range, that is, below the flammability limit, by engineering the nanoparticle size.


The RanGTP gradient - a GPS for the mitotic spindle.
The GTPase Ran has a key role in nuclear import and export, mitotic spindle assembly and nuclear envelope formation. The cycling of Ran between its GTP- and GDP-bound forms is catalyzed by the chromatin-bound guanine nucleotide exchange factor RCC1 and the cytoplasmic Ran GTPase-activating protein RanGAP. The result is an intracellular concentration gradient of RanGTP that equips eukaryotic cells with a ;genome-positioning system' (GPS). The binding of RanGTP to nuclear transport receptors (NTRs) of the importin beta superfamily mediates the effects of the gradient and generates further downstream gradients, which have been elucidated by fluorescence resonance energy transfer (FRET) imaging and computational modeling. The Ran-dependent GPS spatially directs many functions required for genome segregation by the mitotic spindle during mitosis. Through exportin 1, RanGTP recruits essential centrosome and kinetochore components, whereas the RanGTP-induced release of spindle assembly factors (SAFs) from importins activates SAFs to nucleate, bind and organize nascent spindle microtubules. Although a considerable fraction of cytoplasmic SAFs is active and RanGTP induces only partial further activation near chromatin, bipolar spindle assembly is robustly induced by cooperativity and positive-feedback mechanisms within the network of Ran-activated SAFs. The RanGTP gradient is conserved, although its roles vary among different cell types and species, and much remains to be learned regarding its functions.


Neurotrophins, cytokines, oxidative parameters and funcionality in Progressive Muscular Dystrophies.
We investigated the levels of brain derived-neurotrophic factor (BDNF), cytokines and oxidative parameters in serum and tried to correlate them with the age and functionality of patients with Progressive Muscle Dystrophies (PMD). The patients were separated into six groups (case and controls pared by age and gender), as follows: Duchenne Muscular Dystrophy (DMD); Steinert Myotonic Dystrophy (SMD); and Limb-girdle Muscular Dystrophy type-2A (LGMD2A). DMD patients (± 17.9 years old) had a decrease of functionality, an increase in the IL-1β and TNF-α levels and a decrease of IL-10 levels and superoxide dismutase activity in serum. SMD patients (± 25.8 years old) had a decrease of BDNF and IL-10 levels and superoxide dismutase activity and an increase of IL-1β levels in serum. LGMD2A patients (± 27.7 years old) had an decrease only in serum levels of IL-10. This research showed the first evidence of BDNF involvement in the SMD patients and a possible unbalance between pro-inflammatory and anti-inflammatory cytokine levels, along with decreased superoxide dismutase activity in serum of DMD and SMD patients.


A novel pathogenic mutation of MeCP2 impairs chromatin association independent of protein levels.
Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance and its DNA binding, and G118E mice manifest RTT-like symptoms seen in the patient, affirming the pathogenicity of this mutation. Using live-cell and single-molecule imaging, we found that G118E mutation alters MeCP2's chromatin interaction properties in live neurons independently of its effect on protein levels. Here we report the generation and characterization of RTT models of a male hypomorphic variant and reveal new insight into the mechanism by which this pathological mutation affects MeCP2's chromatin dynamics. Our ability to quantify protein dynamics in disease models lays the foundation for harnessing high-resolution single-molecule imaging as the next frontier for developing innovative therapies for RTT and other diseases.


Functional roles of Grainyhead-like transcription factors in renal development and disease.
Proper renal function relies on the tightly regulated development of nephrons and collecting ducts. This process, known as tubulogenesis, involves dynamic cellular and molecular changes that instruct cells to form highly organized tubes of epithelial cells which compartmentalize the renal interstitium and tubular lumen via assembly of a selective barrier. The integrity and diversity of the various renal epithelia is achieved via formation of intercellular protein complexes along the apical-basal axis of the epithelial cells. In recent years, the evolutionarily conserved family of Grainyhead-like (GRHL) transcription factors which encompasses three mammalian family members (Grainyhead-like 1, 2, 3) has emerged as a group of critical regulators for organ development, epithelial differentiation, and barrier formation. Evidence from transgenic animal models supports the presence of Grainyhead-like-dependent transcriptional mechanisms that promote formation and maintenance of epithelial barriers in the kidney. In this review, we highlight different Grhl-dependent mechanisms that modulate epithelial differentiation in the kidney. Additionally, we discuss how disruptions in these mechanisms result in impaired renal function later in life.


Investigations of the intermolecular forces between RDX and polyethylene by force-distance spectroscopy and molecular dynamics simulations.
The development of novel nanoenergetic materials with enhanced bulk properties requires an understanding of the intermolecular interactions occurring between molecular components. We investigate the surface interactions between 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX) and polyethylene (PE) crystals on the basis of combined use of molecular dynamics (MD) simulations and force-distance spectroscopy, in conjunction with Lifshitz macroscopic theory of van der Waals forces between continuous materials. The binding energy in the RDX-PE system depends both on the degree of PE crystallinity and on the RDX crystal face. Our MD simulations yield binding energies of approximately 132 and 120 mJ/m(2) for 100% amorphous and 100% crystalline PE on RDX (210), respectively. The average value is about 36% greater than our experimental value of 81 ± 15 mJ/m(2) for PE (∼48% amorphous) on RDX (210). By comparison, Liftshitz theory predicts a value of about 79 mJ/m(2) for PE interacting with RDX. Our MD simulations also predict larger binding energies for both amorphous and crystalline PE on RDX (210) compared to the RDX (001) surface. Analysis of the interaction potential indicates that about 60% of the binding energy in the PE-RDX system is due to attractive interactions between HPE-ORDX and CPE-NRDX pairs of atoms. Further, amorphous PE shows a much longer interaction distance than crystalline PE with the (210) and (001) RDX surfaces due to the possibility of larger polymer elongations in the case of amorphous PE as strain is applied. Also, we report estimates of the binding energies of energetic materials RDX and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) with PE, propylene, polystyrene, and several fluorine-containing polymers using Lifshitz theory and compare these with reported MD calculations.


[New radiological techniques to investigate patients suffering from chronic kidney disease].
Radiological investigations using gadolinium or intravenous iodinated contrast products are used cautiously in patients suffering from chronic kidney disease because of their risk of acute kidney injury and systemic nephrogenic fibrosis. In this article, we review several radiological alternatives that can be useful to obtain renal anatomical and/or functional information in this patient population. The basic principles, indications, and advantages and limitations of Doppler ultrasound with measurement of the resistance index, contrast-enhanced ultrasound, and a technique called BOLD-MRI (blood-oxygenation level dependent-MRI) are discussed.


18F-FAZA PET/CT Hypoxia Imaging of High-Grade Glioma Before and After Radiotherapy.
A 57 year-old man underwent MRI with dynamic susceptibility contrast and dynamic contrast-enhanced perfusion for neurological symptoms suggesting the diagnosis of high-grade glioma. A F-FAZA PET/CT was performed because of the enrollment in a prospective clinical trial. Subsequent radiotherapy treatment has been planned based on conventional imaging; moreover, a F-FAZA PET/CT-guided treatment planning highlighting hypoxic regions has been simulated. After radiotherapy treatment, the man underwent MRI and F-FAZA PET/CT, showing partial response.


Reduced estriol and dehydroepiandrosterone sulphate plasma levels in methadone-addicted pregnant women.
The plasma levels of human chorionic somatomammotropin (hCS), estriol (E3), dehydroepiandrosterone sulphate (DHA-S), cortisol and the circadian changes of the two last adrenal hormones were studied in 25 pregnant methadone-addicted women (MA) and 21 pregnant drug-naive controls (C) at different periods of gestation and in 13 non-pregnant women (7 MA and 6 drug-naive). MA pregnant women showed normal plasma levels of hCS both at the second (6.9 +/- 0.1 vs. 7.2 +/- 0.1 micrograms/ml) and third (9.6 +/- 0.2 vs. 9.3 +/- 0.2) trimester, while plasma concentrations of E3 at term were lower than normal (MA: 4.4 +/- 0.8; C: 8.2 +/- 1.0 ng/ml, P less than 0.05). DHA-S plasma levels of MA pregnant women were half the normal values in three trimesters of gestation, while there were no differences in non-pregnant subjects. Circadian variations of cortisol and DHA-S plasma levels were present in both MA and C. The blunted DHA-S but normal cortisol plasma levels found in MA pregnant women indicate that opiate abuse interferes with adrenal function, mainly of the fetus. Due to the scarce availability of adrenal precursors, these data suggest that E3 measurements should not be considered as a useful index of fetal well-being in the presence of opiate addiction.


Aerotitis in air travel.
In the years 1964-1969, 2,015 cases of aerotitis were reported as an occupational disease in California. Most of the cases were in women flight crew members on commercial airlines (women predominate in such crews). Cases were also reported in passengers. Upper respiratory infection frequently appeared to be a predisposing event.


Synchronous bilateral testicular tumour: nonseminomatous germ cell tumours and contralateral benign tumours.
Synchronous bilateral testicular germ cell tumours (TGCT) of different origin are very rare; the simultaneous appearance of a TGCT with a contralateral benign non-germ cell tumour represents an even more seldom event. We report on three patients with nonseminomatous TGCT and a contralateral benign testis tumour being Leydig cell tumour, leiomyoma and epidermopid cyst, respectively. Patients were treated by radical orchiectomy in one case and by enucleation resection of the tumour in two cases. After follow-up of more than 5 years all patients are NED; no local recurrence occurred in the patients treated by tumour enucleation with their endogenous testosterone production being maintained. Although very rare the simultaneous appearance of a malignant TGCT and a contralateral benign intratesticular mass should be considered with bilateral tumours. Frozen section examination of the tumours might enable an organ sparing approach in benign testis tumours thereby maintaining endogenous testosterone production and fertility.


Repurposing Didanosine as a Potential Treatment for COVID-19 Using Single-Cell RNA Sequencing Data.
As of today (7 April 2020), more than 81,000 people around the world have died from the coronavirus disease 19 (COVID-19) pandemic. There is no approved drug or vaccine for COVID-19, although more than 10 clinical trials have been launched to test potential drugs. In an urgent response to this pandemic, I developed a bioinformatics pipeline to identify compounds and drug candidates to potentially treat COVID-19. This pipeline is based on publicly available single-cell RNA sequencing (scRNA-seq) data and the drug perturbation database "Library of Integrated Network-Based Cellular Signatures" (LINCS). I developed a ranking score system that prioritizes these drugs or small molecules. The four drugs with the highest total score are didanosine, benzyl-quinazolin-4-yl-amine, camptothecin, and RO-90-7501. In conclusion, I have demonstrated the utility of bioinformatics for identifying drugs than can be repurposed for potentially treating COVID-19 patients.


Transient elastography to assess hepatic fibrosis in hemodialysis chronic hepatitis C patients.
Although percutaneous liver biopsy (PLB) is the gold standard for staging hepatic fibrosis in hemodialysis patients with chronic hepatitis C (CHC) before renal transplantation or antiviral therapy, concerns exist about serious postbiopsy complications. Using transient elastography (TE, Fibroscan(®)) to predict the severity of hepatic fibrosis has not been prospectively evaluated in these patients. A total of 284 hemodialysis patients with CHC were enrolled. TE and aspartate aminotransferase-to-platelet ratio index (APRI) were performed before PLB. The severity of hepatic fibrosis was staged by METAVIR scores ranging from F0 to F4. Receiver operating characteristic curves were used to assess the diagnostic accuracy of TE and APRI, taking PLB as the reference standard. The areas under curves of TE were higher than those of APRI in predicting patients with significant hepatic fibrosis (≥F2) (0.96 versus 0.84, P<0.001), those with advanced hepatic fibrosis (≥F3) (0.98 versus 0.93, P=0.04), and those with cirrhosis (F4) (0.99 versus 0.92, P=0.13). Choosing optimized liver stiffness measurements of 5.3, 8.3, and 9.2 kPa had high sensitivity (93-100%) and specificity (88-99%), and 87, 97, and 93% of the patients with a fibrosis stage of ≥F2, ≥F3, and F4 were correctly diagnosed without PLB, respectively. TE is superior to APRI in assessing the severity of hepatic fibrosis and can substantially decrease the need of staging PLB in hemodialysis patients with CHC.


Overview of publicly funded managed behavioral health care.
Using MEDLINE and other Internet sources, the authors perform a systematic review of published literature. A total of 109 articles and reports are identified and reviewed that address the development, implementation, outcomes, and trends related to Managed behavioral health care (MBHC). MBHC remains a work in progress. States have implemented their MBHC programs in a number of ways, making interstate comparisons challenging. While managed behavioral health care can lower costs and increase access, ongoing concerns about MBHC include potential incentives to under-treat those with more severe conditions due to the nature of risk-based contracting, the tendency to focus on acute care, difficulties assuring quality and outcomes consistently across regions, and a potential cost-shift to other public agencies or systems. Success factors for MBHC programs appear to include stakeholder involvement in program and policy development, effective contract development and management, and rate adequacy.


Supraglottic subepithelial benign mass lesions: Focus on clinical features of sialolipoma-like lesion.
Sialolipoma has been classified as a benign soft tissue lesion in the 2017 World Health Organization classification of head and neck tumors. To our knowledge, only one case of laryngeal sialolipoma has been reported in the English literature. We conducted a retrospective study to identify clinical characteristics of supraglottic sialolipoma-like lesion and differentiate it from other supraglottic subepithelial masses. Medical records of 16 patients with supraglottic subepithelial benign mass lesions who underwent histological evaluation between 2003 and 2019 were retrospectively analyzed. Sialolipoma-like lesion was defined as a local finding of a well-circumscribed gross mass with pathological presence of salivary gland-like parenchymal lobules with evenly interspersed adipose tissue. Eight patients showed histological positivity for sialolipoma-like lesion, 3 for amyloidosis, 2 for hemangioma, and 1 each for cyst, lymphoid hyperplasia, and chondrometaplasia. Sialolipoma-like lesion tended to be predominant among men; those affected had a mean age of 52.8 (range, 39-74) years. By contrast, among patients with amyloidosis, the ratio of men to women was 1:2 (100% vs. 33%; p = 0.055). Fiberscopic examination of all patients with sialolipoma-like lesions identified well-circumscribed, yellowish masses, closely resembling local amyloidosis findings. Sialolipoma-like lesion was associated with a significantly higher body-mass index (BMI; 27.4 ± 2.8 kg/m2) than amyloidosis (21.6 ± 1.4 kg/m2; p = 0.014). The transoral approach was used for lesion resection in all patients with sialolipoma-like lesion. No patient experienced postoperative recurrence. Laryngeal sialolipoma-like lesion might be more prevalent than was previously reported, and histological examination is important to differentiate it from amyloidosis. Supraglottic sialolipoma-like lesion must be differentially diagnosed in patients with high BMI presenting with well-circumscribed, yellowish supraglottic masses.


Baculovirus expression of the human papillomavirus type 16 capsid proteins: detection of L1-L2 protein complexes.
The human papillomavirus (HPV) type 16 major capsid proteins L1 and L2 have been produced in a baculovirus expression system. Both proteins are expressed at a high level and can be readily solubilized. The L1 capsid protein migrates close to its expected Mr of 60K. On the other hand L2 exhibits a much higher Mr migrating at 73K, which is considerably greater than its predicted Mr of 50K. The identity of both proteins has been confirmed also by Western blot analysis. Both proteins are produced in drastically reduced amounts in the presence of tunicamycin. In addition both L1 and L2 show interesting patterns of phosphorylation. L1 is phosphorylated only weakly and this appears to be quite labile, whereas L2 is very heavily phosphorylated and this, in contrast, appears to be very stable. We have also made use of a dual expression vector for co-expressing the L1 and L2 proteins within the same baculovirus-infected cell. The results obtained from this system demonstrate the presence of protein complexes forming between the two capsid proteins. These studies indicate that at least the initial events in capsid assembly of HPVs can occur in the absence of viral DNA.


Studies of the mechanism of amniotic sac puncture-induced limb abnormalities in mice.
The principal advantage of chorionic villus sampling (cvs) over amniocentesis for the determination of the genetic constitution of the embryo is that it may be undertaken earlier in pregnancy. If carried out too early in pregnancy, it has the risk of inducing craniofacial and limb abnormalities, a condition termed the oromandibulofacial limb hypogenesis (OMFL) syndrome in genetically normal infants. It is believed that the defects observed have a vascular origin, possibly due to anoxia of tissues due to fetal blood loss or thrombus formation at the site of biopsy with distal embolization. We believe that this does not adequately explain the findings from the experimental animal literature involving amniotic sac puncture (ASP). Based on these experimental findings, we have hypothesised that (i) the defects observed following cvs may result from the consequences of oligohydramnios following the inadvertent puncturing of the amniotic sac during this procedure, and (ii) that cleft palate and the postural limb defects observed (e.g., clubfoot and clubhand) are secondary to embryonic/fetal compression. Our experimental studies shed new light on the mechanism of induction of the limb defects seen, but particularly syndactyly. Evidence of hypoperfusion of the peripheral part of the developing limb bud is observed, which interferes with apoptosis that occurs in the digital interzones, or induces an abnormal degree of cellular proliferation and/or tissue regeneration in these sites, possibly because of over-expression of critical genes involved in limb pattern specification. Cleft palate, tail abnormalities and abnormalities of sternal ossification are also observed in our model.


Molecular evidence for a role for K(+)-Cl(-) cotransporters in the kidney.
K(+)-Cl(-) cotransporter (KCC) isoforms 3 (KCC3) and 4 (KCC4) are expressed at the basolateral membrane of proximal convoluted tubule cells, and KCC4 is present in the basolateral membrane of the thick ascending loop of Henle's limb and α-intercalated cells of the collecting duct. Little is known, however, about the physiological roles of these transporters in the kidney. We evaluated KCC3 and KCC4 mRNA and protein expression levels and intrarenal distribution in male Wistar rats or C57 mice under five experimental conditions: hyperglycemia after a single dose of streptozotocin, a low-salt diet, metabolic acidosis induced by ammonium chloride in drinking water, and low- or high-K(+) diets. Both KCC3 mRNA and protein expression were increased during hyperglycemia in the renal cortex and at the basolateral membrane of proximal tubule cells but not with a low-salt diet or acidosis. In contrast, KCC4 protein expression was increased by a low-sodium diet in the whole kidney and by metabolic acidosis in the renal outer medulla, specifically at the basolateral membrane of α-intercalated cells. The increased protein expression of KCC4 by a low-salt diet was also observed in WNK4 knockout mice, suggesting that upregulation of KCC4 in these circumstances is not WNK4 dependent. No change in KCC3 or KCC4 protein expression was observed under low- or high-K(+) diets. Our data are consistent with a role for KCC3 in the proximal tubule glucose reabsorption mechanism and for KCC4 in salt reabsorption of the thick ascending loop of Henle's loop and acid secretion of the collecting duct.


Problems with oral formulations prescribed to children: a focus group study of healthcare professionals.
There is evidence to suggest that adherence with prescribed medication is lower amongst adolescents and children than in adults. Medication adherence rates between 11 and 93 % in paediatric patients have been reported. More research needs to be carried out in order to understand why medicines adherence is low and how adherence can be improved in children with long-term conditions. Personal communication with paediatricians in secondary care has highlighted that problems are most likely to be encountered by parents, carers, nurses and children themselves when administering medicines for prevalent long-term childhood conditions. To explore problems with oral medicines prescribed to paediatric patients from the perspectives of medical practitioners, pharmacists and nurses. Setting Two NHS trusts in the West Midlands, UK. Four focus groups (FG) were conducted. Five nurses, eight medical practitioners and six pharmacists participated in focus groups. The themes explored were problems experienced when prescribing, dispensing and administering oral medicines for children. Main outcome measure Themes evolving from Healthcare professionals reports on problems with administering medicines to paediatric patients. Two main themes: sensory and non-sensory emerged from the data. Included within these were taste, texture, colour, smell, size, swallowing, quantity, volume and manipulation with food. Taste was the most commonly reported barrier to medicines administration. Texture was reported to be a significant problem for the learning disability population. Medicines manipulation techniques were revealed across the groups, yet there was limited knowledge regarding the evidence base for such activity. Problems surrounding the supply of Specials medicines were discussed in-depth by the pharmacists. Organoleptic and physical properties of medicines are key barriers to medicines administration. A robust scientific evidence-based approach is warranted to inform standardised protocols guiding healthcare professionals to support safe and effective medicines manipulation across all settings. Pharmacists' knowledge of Specials medicines needs to be recognised as a valuable resource for doctors. Findings of this study should help to optimise paediatric prescribing and direct future formulation work.


Rapamycin and the transcription factor C/EBPbeta as a switch in osteoclast differentiation: implications for lytic bone diseases.
Lytic bone diseases and in particular osteoporosis are common age-related diseases characterized by enhanced bone fragility due to loss of bone density. Increasingly, osteoporosis poses a major global health-care problem due to the growth of the elderly population. Recently, it was found that the gene regulatory transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) is involved in bone metabolism. C/EBPbeta occurs as different protein isoforms of variable amino terminal length, and regulation of the C/EBPbeta isoform ratio balance was found to represent an important factor in osteoclast differentiation and bone homeostasis. Interestingly, adjustment of the C/EBPbeta isoform ratio by the process of translational control is downstream of the mammalian target of rapamycin kinase (mTOR), a sensor of the nutritional status and a target of immunosuppressive and anticancer drugs. The findings imply that modulating the process of translational control of C/EBPbeta isoform expression could represent a novel therapeutic approach in osteolytic bone diseases, including cancer and infection-induced bone loss.


Experimental and Theoretical Investigations on Structural and Vibrational Properties of Melilite-Type Sr2ZnGe2O7 at High Pressure and Delineation of a High-Pressure Monoclinic Phase.
We report a combined experimental and theoretical study of melilite-type germanate, Sr2ZnGe2O7, under compression. In situ high-pressure X-ray diffraction and Raman scattering measurements up to 22 GPa were complemented with first-principles theoretical calculations of structural and lattice dynamics properties. Our experiments show that the tetragonal structure of Sr2ZnGe2O7 at ambient conditions transforms reversibly to a monoclinic phase above 12.2 GPa with ∼1% volume drop at the phase transition pressure. Density functional calculations indicate the transition pressure at ∼13 GPa, which agrees well with the experimental value. The structure of the high-pressure monoclinic phase is closely related to the ambient pressure phase and results from a displacive-type phase transition. Equations of state of both tetragonal and monoclinic phases are reported. Both of the phases show anisotropic compressibility with a larger compressibility in the direction perpendicular to the [ZnGe2O7](2-) sheets than along the sheets. Raman-active phonons of both the tetragonal and monoclinic phases and their pressure dependences were also determined. Tentative assignments of the Raman modes of the tetragonal phase were discussed in the light of lattice dynamics calculations. A possible irreversible second phase transition to a highly disordered or amorphous state is detected in Raman scattering measurements above 21 GPa.


Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype.
Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders.


Defining the balance point between conservation and development.
In the face of the current global ecological crisis and the threats it poses to human survival and security, the fundamental solution is to resolve the deep contradiction between conservation and economic development. We considered the 3 key and basic questions of why to protect, how much to protect, and where to protect natural areas. Human survival depends on functioning ecosystems and the ecosystem services they provide. In this regard, conserving core biodiversity conservation priority areas (BCPAs) can provide maximum conservation benefit. The goals of protected area (PA) systems globally and nationally must be clearly defined so as to sustain the survival and development of people and to coordinate and balance other objectives with this goal at the center. There is an urgent need to study, calculate, and define the extent of the natural world to ensure the well-being of people. We call this area over which natural areas of land and sea extend across the world or a country nature proportion (N%). Especially, a minimum area that ensures human survival should be protected, and we suggest that this area should cover core BCPAs so that it can achieve the maximum conservation benefit. These recommendations could be applied at global or national levels. The Chinese government proposes "developing a protected-area system composed mainly of national parks," and it has unified the administration of PAs into a central management authority. At this key time in the reform of the PA system, should this proposal be adopted, conservation will garner the greatest social consensus and support, and planning at the national level for BCPA coverage will be improved. We believe these recommendations are critical for China and other countries and extremely important for the world because they will pave the way toward a balance between nature conservation and human development as the projected human population reaches 10 billion by 2050.


A Systematic Review of Sociodemographic, Macroeconomic, and Health Resources Factors on Life Expectancy.
This review was aimed at systematically synthesizing and appraising the existing literature of sociodemographic, macroeconomic, and health resources factors on life expectancy. A systematic literature search of English databases, that is, PubMed/MEDLINE were scrutinized for exploring sociodemographic, macroeconomic, and health resources factors on life expectancy. The literature search was conducted in January 2020, covering a total of 46 articles from 2004 to 2019 met the review criteria, which were fully discussed subsequently. Among sociodemographic factors, infant mortality rate, literacy rate, education level, socioeconomic status, population growth, and gender inequality have a significant impact on life expectancy. Gross domestic product, Gini, income level, unemployment rate, and inflation rate are the main macroeconomic factors that significantly correlated with life expectancy. Among various health care resources, health care facilities, the number of the health care profession, public health expenditure, death rates, smoking rate, pollution, and vaccinations had a significant correlation with life expectancy. The systematic review showed general conformity of different studies, with a significant association between life expectancy and factors comprising several sociodemographic, macroeconomic, and various health care variables. This review found that only one study examined factors affecting life expectancy in Arabic countries. More studies on this region to fill this research gap were highly recommended.


Chemokines and the arrest of lymphocytes rolling under flow conditions.
Circulating lymphocytes are recruited from the blood to the tissue by rolling along the endothelium until being stopped by a signaling event linked to the Gialpha subunit of a heterotrimeric GTP-binding protein; that event then triggers rapid integrin-dependent adhesion. Four chemokines are now shown to induce such adhesion to intercellular adhesion molecule-1 and to induce arrest of rolling cells within 1 second under flow conditions similar to those of blood. SDF-1 (also called PBSF), 6-C-kine (also called Exodus-2), and MIP-3beta (also called ELC or Exodus-3) induced adhesion of most circulating lymphocytes, including most CD4+ T cells; and MIP-3alpha (also called LARC or Exodus-1) triggered adhesion of memory, but not naïve, CD4+ T cells. Thus, chemokines can regulate the arrest of lymphocyte subsets under flowing conditions, which may allow them to control lymphocyte-endothelial cell recognition and lymphocyte recruitment in vivo.


Stability-indicating methods for the determination of racecadotril in the presence of its degradation products.
Three stability-indicating methods were developed for the determination of racecadotril (RCT) in the presence of its alkaline degradation products. The first was an HPLC method in which efficient chromatographic separation was achieved on a C18 analytical column and a mobile phase of acetonitrile-methanol-water-acetic acid (52:28:20:0.1, v/v/v/v). Linearity was obtained in the range of 4-40 microg/mL with mean accuracy of 99.5 +/- 0.88%. The second method was a densitometric evaluation of thin-layer chromatograms of the drug using a mobile phase of isopropanol-ammonia (33%)-n-hexane (9:0.5:20, v/v/v). The chromatograms were scanned at 232 nm, a wavelength at which RCT can be readily separated from its degradation products and determined in the range of 2-20 microg per spot with mean accuracy of 99.5 +/- 0.56%. The third method is based on the use of first-derivative spectrophotometry (D1) at 240 nm, and the drug was determined in the range of 5-40 microg/mL with mean accuracy of 99.2 +/- 1.02%. The three methods provided satisfactory recovery of the intact drug (100.8 +/- 0.82, 100.4 +/- 0.55, and 99.9 +/- 0.72%, respectively) in the presence of up to 90% of its degradation products. Determination was also successful when analyzing RCT in a formulation in the form of acetorphan packets. Results were statistically analyzed and found to be in accordance with those given by a reported method.


Antimicrobial activities and toxicity of crude extract of the Psophocarpus tetragonolobus pods.
The extract of the Psophocarpus tetragonolobus pods has been tested for antimicrobial activity in a disk diffusion assay on eight human pathogenic bacteria and two human pathogenic yeasts. The extracts of P. tetragonolobus possessed antimicrobial activity against all tested strains. The ethanolic extract of P. tetragonolobus pods was further tested for in vivo brine shrimp lethality test and in vitro sheep erythrocyte cytotoxic assay. The brine shrimp lethality test exhibited no significant toxicity (LC(50)=1.88 mg/ml) against Artemia salina, whereas sheep erythrocyte test showed significant toxicity. The reason for haemolysis of erythrocyte was discussed. The P. tetragonolobus extract with high LC(50) value signified that this plant is not toxic to human. This result also suggested that the ethanolic extract of P. tetragonolobus pods is potential source for novel antimicrobial compounds.


Precise and fuzzy coding by olfactory sensory neurons.
The exact nature of the olfactory signals that arrive in the brain from the periphery, and their reproducibility, remain essentially unknown. In most organisms, the sheer number of olfactory sensory neurons (OSNs) makes it impossible to measure the individual responses of the entire population. We measured the individual in situ electrophysiological activity of OSNs in Drosophila larvae, in response to stimulation with 10 aliphatic odors (alcohols and esters). We studied control larvae (a total of 296 OSNs) and larvae with a single functional OSN, created using the Gal4-upstream activator sequence system. Most OSNs showed consistent, precise responses (either excitation or inhibition) in response to a given odor. Some OSNs also showed qualitatively variable responses ("fuzzy coding"). This robust variability was an intrinsic property of these neurons: it was not attributable to odor type, concentration, stimulus duration, genotype, or interindividual differences, and was seen in control larvae and in larvae with one and two functional OSNs. We conclude that in Drosophila larvae the peripheral code combines precise coding with fuzzy, stochastic responses in which neurons show qualitative variability in their responses to a given odor. We hypothesize that fuzzy coding occurs in other organisms, is translated into differing degrees of activation of the glomeruli, and forms a key component of response variability in the first stages of olfactory processing.


Depressed Synaptic Transmission and Reduced Vesicle Release Sites in Huntington's Disease Neuromuscular Junctions.
Huntington's disease (HD) is a progressive and fatal degenerative disorder that results in debilitating cognitive and motor dysfunction. Most HD studies have focused on degeneration of the CNS. We previously discovered that skeletal muscle from transgenic R6/2 HD mice is hyperexcitable due to decreased chloride and potassium conductances. The progressive and early onset of these defects suggest a primary myopathy in HD. In this study, we examined the relationship between neuromuscular transmission and skeletal muscle hyperexcitability. We used an ex vivo preparation of the levator auris longus muscle from male and female late-stage R6/2 mice and age-matched wild-type controls. Immunostaining of the synapses and molecular analyses revealed no evidence of denervation. Physiologically, we recorded spontaneous miniature endplate currents (mEPCs) and nerve-evoked EPCs (eEPCs) under voltage-clamp, which, unlike current-clamp records, were independent of the changes in muscle membrane properties. We found a reduction in the number of vesicles released per action potential (quantal content) in R6/2 muscle, which analysis of eEPC variance and morphology indicate is caused by a reduction in the number of vesicle release sites (n) rather than a change in the probability of release (prel). Furthermore, analysis of high-frequency stimulation trains suggests an impairment in vesicle mobilization. The depressed neuromuscular transmission in R6/2 muscle may help compensate for the muscle hyperexcitability and contribute to motor impersistence.SIGNIFICANCE STATEMENT Recent evidence indicates that Huntington's disease (HD) is a multisystem disorder. Our examination of neuromuscular transmission in this study reveals defects in the motor nerve terminal that may compensate for the muscle hyperexcitability in HD. The technique we used eliminates the effects of the altered muscle membrane properties on synaptic currents and thus provides hitherto the most detailed analysis of synaptic transmission in HD. Clinically, the striking depression of neurotransmission we found may help explain the motor impersistence in HD patients. Therapies that target the highly accessible peripheral nerve and muscle system provide a promising new avenue to lessen the debilitating motor symptoms of HD.


Upper thoracic spine arthroplasty via the anterior approach.
Significant progress has been made in lumbar and cervical disc replacement therapy. Several cervical disc prostheses have recently gained FDA approval. Although arthroplasty has not been previously described in the thoracic spine, selected patients with long-segment fusion to the level of C-7 have altered cervicothoracic and upper thoracic biomechanics and may benefit from motion-preservation therapy for T1-2 disc herniation. Currently, FDA-approved prostheses are indicated only for patients with single-level degenerative disc disease between C-3 and C-7 and no history of cervical arthrodesis. The authors describe a 52-year-old woman who had previously undergone C3-7 fusion and returned 4 years later with symptoms of C-8 myeloradiculopathy and radiological evidence of T1-2 degenerative disc disease. She underwent T1-2 arthroplasty in which a Prestige artificial cervical disc was placed via an anterior cervicothoracic approach. Motion at C7-T1 and T1-2 was preserved, and the patient made an excellent clinical recovery.


Improvement of color reproduction in color digital holography by using spectral estimation technique.
We propose a color digital holography by using spectral estimation technique to improve the color reproduction of objects. In conventional color digital holography, there is insufficient spectral information in holograms, and the color of the reconstructed images depend on only reflectances at three discrete wavelengths used in the recording of holograms. Therefore the color-composite image of the three reconstructed images is not accurate in color reproduction. However, in our proposed method, the spectral estimation technique was applied, which has been reported in multispectral imaging. According to the spectral estimation technique, the continuous spectrum of object can be estimated and the color reproduction is improved. The effectiveness of the proposed method was confirmed by a numerical simulation and an experiment, and, in the results, the average color differences are decreased from 35.81 to 7.88 and from 43.60 to 25.28, respectively.


Social touch deprivation during COVID-19: effects on psychological wellbeing and craving interpersonal touch.
Social touch has positive effects on social affiliation and stress alleviation. However, its ubiquitous presence in human life does not allow the study of social touch deprivation 'in the wild'. Nevertheless, COVID-19-related restrictions such as social distancing allowed the systematic study of the degree to which social distancing affects tactile experiences and mental health. In this study, 1746 participants completed an online survey to examine intimate, friendly and professional touch experiences during COVID-19-related restrictions, their impact on mental health and the extent to which touch deprivation results in craving touch. We found that intimate touch deprivation during COVID-19-related restrictions is associated with higher anxiety and greater loneliness even though this type of touch is still the most experienced during the pandemic. Moreover, intimate touch is reported as the type of touch most craved during this period, thus being more prominent as the days practising social distancing increase. However, our results also show that the degree to which individuals crave touch during this period depends on individual differences in attachment style: the more anxiously attached, the more touch is craved; with the reverse pattern for avoidantly attached. These findings point to the important role of interpersonal and particularly intimate touch in times of distress and uncertainty.


Exploring anxiety levels in healthcare workers during COVID-19 pandemic: Turkey sample.
As in the whole world, the Novel Coronavirus (COVID-19) pandemic poses many threats to healthcare workers in our country too, which leads to anxiety in healthcare workers. This study was conducted to explore the anxiety levels of healthcare workers during the COVID-19 pandemic. The study is a cross-sectional study. The population consisted of health care workers employed in hospitals in seven regions in Turkey. All volunteer healthcare workers were included in the study, and 356 healthcare workers responded to the questionnaire. The data were collected using the State Anxiety Inventory and a questionnaire created by the researchers using an online questionnaire between 10 May 2020 and 15 May 2020. In the evaluation of the data, mean, standard deviation, percentages, t-test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used. 33% of healthcare workers did not have anxiety, 50% had mild, and 17% had severe anxiety. The anxiety scores of those who were nurses (p < 0.001), who were working in the emergency room (p < 0.001), who were involved in treatment for COVID-19 patients (p = 0.040), who left their homes to prevent transmission to their families and relatives during the pandemic (p = 0.038), and whose working hours had changed (p = 0.036) were found to be significantly higher. It was observed that there was a positive and significant relationship between the fear of death and disease transmission, uncertainty, loneliness, anger, and hopelessness, and anxiety levels in healthcare workers. The main factors that significantly affected the anxiety levels of healthcare workers were male gender, weekly working hours, the presence of chronic diseases, and feelings of anger and uncertainty. In conclusion, during the COVID-19 pandemic, healthcare workers experienced some negative emotions, their anxiety levels increased, and they were psychologically affected. Planning psychosocial interventions for healthcare workers in the high-risk group will make significant contributions to the health system.


Frankliniella occidentalis pathogenic fungus Lecanicillium interacts with internal microbes and produces sublethal effects.
Frankliniella occidentalis (Thysanoptera: Thripidae) is a pest that feeds on various crops worldwide. A prior study identified Lecanicillium attenuatum and L. cauligalbarum as pathogens of F. occidentalis. Unfortunately, the potential of these two entomopathogenic fungi for the biocontrol of F. occidentalis has not been effectively evaluated. The internal microbes (endosymbionts and the gut microbiota) of insects, especially gut bacteria, are crucial in regulating the interactions between the host and intestinal pathogens. The role of thrips internal microbes in the infection of these two entomopathogenic fungi is also unknown. Therefore, biological control of thrips is immediately needed, and to accomplish that, an improved understanding of the internal microbes of thrips against Lecanicillium infection is essential. The virulence of the two pathogenic fungi against F. occidentalis increased with the conidia concentration. Overall, the LC50 of L. cauligalbarum was lower than that of L. attenuatum, and the pathogenicity degree was adult > pupa > nymphs. The activities of protective enzymes include superoxide dismutase (SOD), catalase (CAT), peroxidase (POD); detoxification enzymes include polyphenol oxidase (PPO), glutathione s-transferase (GSTs), and carboxylesterase (CarE); hormones include ecdysone and juvenile hormone; and the composition and proportion of microorganisms (fungi and bacteria) in F. occidentalis infected by L. cauligalbarum and L. attenuatum have changed significantly. According to the network correlation results, there was a considerable correlation among the internal microbes (including bacteria and fungi), enzyme activities, and hormones, which indicates that in addition to bacteria, internal fungi of F. occidentalis are also involved in the L. cauligalbarum and L. attenuatum infection process. In addition, the development time of the surviving F. occidentalis exposed to L. cauligalbarum or L. attenuatum was significantly shorter than that of the control group. Furthermore, the intrinsic rate of increase (rm), finite rate of increase (λ), net reproductive rate (R0), mean generation time (T), and gross reproductive rate (GRR) were significantly lower in the treatment groups than in the control group. L. attenuatum and L. cauligalbarum have biocontrol potential against F. occidentalis. In addition to bacteria, internal fungi of F. occidentalis are also involved in the infection process of insect pathogenic fungi. Disruption of the internal microbial balance results in discernible sublethal effects. Such prevention and control potential should not be ignored. These findings provide an improved understanding of physiological responses in thrips with altered immunity against entomopathogenic fungal infections, which can guide us toward the development of novel biocontrol strategies against thrips.


Activation of a PGC-1-related coactivator (PRC)-dependent inflammatory stress program linked to apoptosis and premature senescence.
PGC-1-related coactivator (PRC), a growth-regulated member of the PGC-1 coactivator family, contributes to the expression of the mitochondrial respiratory apparatus. PRC also orchestrates a robust response to metabolic stress by promoting the expression of multiple genes specifying inflammation, proliferation, and metabolic reprogramming. Here, we demonstrate that this PRC-dependent stress program is activated during apoptosis and senescence, two major protective mechanisms against cellular dysfunction. Both PRC and its targets (IL1α, SPRR2D, and SPRR2F) were rapidly induced by menadione, an agent that promotes apoptosis through the generation of intracellular oxidants. Menadione-induced apoptosis and the PRC stress program were blocked by the antioxidant N-acetylcysteine. The PRC stress response was also activated by the topoisomerase I inhibitor 7-ethyl-10-hydroxycamptothecin (SN-38), an inducer of premature senescence in tumor cells. Cells treated with SN-38 displayed morphological characteristics of senescence and express senescence-associated β-galactosidase activity. In contrast to menadione, the SN-38 induction of the PRC program occurred over an extended time course and was antioxidant-insensitive. The potential adaptive function of the PRC stress response was investigated by treating cells with meclizine, a drug that promotes glycolytic energy metabolism and has been linked to cardio- and neuroprotection against ischemia-reperfusion injury. Meclizine increased lactate production and was a potent inducer of the PRC stress program, suggesting that PRC may contribute to the protective effects of meclizine. Finally, c-MYC and PRC were coordinately induced under all conditions tested, implicating c-MYC in the biological response to metabolic stress. The results suggest a general role for PRC in the adaptive response to cellular dysfunction.


Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab.
In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this efficacy, we performed a nonlinear finite element analysis (FEA) of hip and spine quantitative computed tomography (QCT) scans to estimate hip and spine strength in a subset of FREEDOM subjects (n = 48 placebo; n = 51 denosumab) at baseline, 12, 24, and 36 months. We found that, compared with baseline, the finite element estimates of hip strength increased from 12 months (5.3%; p < 0.0001) and through 36 months (8.6%; p < 0.0001) in the denosumab group. For the placebo group, hip strength did not change at 12 months and decreased at 36 months (-5.6%; p < 0.0001). Similar changes were observed at the spine: strength increased by 18.2% at 36 months for the denosumab group (p < 0.0001) and decreased by -4.2% for the placebo group (p = 0.002). At 36 months, hip and spine strength increased for the denosumab group compared with the placebo group by 14.3% (p < 0.0001) and 22.4% (p < 0.0001), respectively. Further analysis of the finite element models indicated that strength associated with the trabecular bone was lost at the hip and spine in the placebo group, whereas strength associated with both the trabecular and cortical bone improved in the denosumab group. In conclusion, treatment with denosumab increased hip and spine strength as estimated by FEA of QCT scans compared with both baseline and placebo owing to positive treatment effects in both the trabecular and cortical bone compartments. These findings provide insight into the mechanism by which denosumab reduces fracture risk for postmenopausal women with osteoporosis.


Dark adaptation and short-wavelength backgrounds decrease perceived size.
The effects of background luminance, contrast, and background wavelength on the perceived size of small line figures were studied at mesopic levels of light adaptation. Perceived size diminished at low levels of background luminance. The effect disappeared at high levels of luminance. Perceived size of luminous circles increased as a logarithmic function of background luminance when the background intensity did not exceed 25 td(1). The strength of the size effect decreased as a function of circle diameter from 0-125 to 2 deg of visual angle(2). Perceived size of small luminous circles, subtending less than 0-5 deg, also increased as a function of contrast at low values of contrast but at very high values of contrast there was a decrease in perceived size. Background luminance had the same effect on the perceived size of circles as on the perceived size of spatial cycles in gratings. Control experiments led to the conclusion that dark adaptation is the primary source of the size effects. The main evidence for this conclusion was obtained from a demonstration that the same background luminance produced either an increase or a decrease in perceived size, depending on the adaptational state of the eye. It was also found that a shift from cone vision to rod vision contributes to the effects, for a stimulus looked smaller on a short-wavelength background than on a long-wavelength background. The size effects can be predicted from the changes of receptive-field properties of single neurones under corresponding conditions of stimulation, if it is assumed that the perception of size is mediated by size-specific channels formed of single neurones. Stimulation that leads to an activation of small receptive fields appears to indicate to the brain the presence of small retinal images. If small receptive fields are experimentally made responsive to larger retinal images, an underestimation of size results.


Plasticity of brain and cognition in older adults.
Aging is typically related to changes in brain and cognition, but the aging process is heterogeneous and differs between individuals. Recent research has started investigating the influence of cognitive and physical training on cognitive performance, functional brain activity, and brain structure in old age. The functional relevance of neural changes and the interactions among these changes following interventions is still a matter of debate. Here we selectively review research on structural and functional brain correlates of training-induced performance changes in healthy older adults and present exemplary longitudinal intervention studies sorted by the type of training applied (i.e., strategy-based training, process-specific training, and physical exercise). Although many training studies have been conducted recently, within each task domain, the number of studies that used comparable methods and techniques to assess behavioral and neural changes is limited. We suggest that future studies should include a multimodal approach to enhance the understanding of the relation between different levels of brain changes in aging and those changes that result from training. Investigating inter-individual differences in intervention-induced behavioral and neuronal changes would provide more information about who would benefit from a specific intervention and why. In addition, a more systematic examination of the time course of training-related structural and functional changes would improve the current level of knowledge about how learning is implemented in the brain and facilitate our understanding of contradictory results.


Bacillus clausii for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Acute diarrhea is a burdensome disease with potentially harmful consequences, especially in childhood. Despite its large use in clinical practice, the efficacy of the probiotic Bacillus clausii in treating acute childhood diarrhea remains unclear. Our objective was to systematically review the efficacy of Bacillus clausii in the treatment of acute childhood diarrhea. The following electronic databases were systematically searched up to October 2017: MEDLINE (via PubMed/OVID), EMBASE (via OVID), Cochrane Central Database of Controlled Trials (via CENTRAL), Google Scholar, and ClinicalTrials.gov. Only randomized controlled trials were included. The overall effect for the meta-analysis was derived by using a random effects model. Six randomized controlled trials (1298 patients) met the eligibility criteria. Data arising from pooled analysis showed that Bacillus clausii significantly reduced the duration of diarrhea (mean difference = -9.12 h; 95% confidence interval [CI]: -16.49 to -1.75, p = 0.015), and the duration of hospitalization (mean difference = -0.85 days; 95% CI: -1.56 to -0.15, p = 0.017), compared with control. There was a trend of decreasing stool frequency after Bacillus clausii administration compared with the control group (mean difference = -0.19 diarrheal motions; 95% CI: -0.43 to -0.06, p = 0.14). Bacillus clausii may represent an effective therapeutic option in acute childhood diarrhea, with a good safety profile.


Murine CENPF interacts with syntaxin 4 in the regulation of vesicular transport.
Syntaxin 4 is a component of the SNARE complex that regulates membrane docking and fusion. Using a yeast two-hybrid screen, we identify a novel interaction between syntaxin 4 and cytoplasmic murine CENPF, a protein previously demonstrated to associate with the microtubule network and SNAP-25. The binding domain for syntaxin 4 in CENPF was defined by yeast two-hybrid assay and co-immunoprecipitation. Confocal analyses in cell culture reveal a high degree of colocalization between endogenously expressed proteins in interphase cells. Additionally, the endogenous SNARE proteins can be isolated as a complex with CENPF in immunoprecipitation experiments. Further analyses demonstrate that murine CENPF and syntaxin 4 colocalize with components of plasma membrane recycling: SNAP-25 and VAMP2. Depletion of endogenous CENPF disrupts GLUT4 trafficking whereas expression of a dominant-negative form of CENPF inhibits cell coupling. Taken together, these studies demonstrate that CENPF provides a direct link between proteins of the SNARE system and the microtubule network and indicate a diverse role for murine CENPF in vesicular transport.


Helicobacter pylori vaccine: from past to future.
Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.


Neurocognition in individuals at high familial risk of mood disorders with or without subsequent onset of depression.
Neurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset. A neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility. Reduced long delay verbal memory and extradimensional set-shifting performance across both time points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional set-shifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups. Reduced verbal memory and cognitive flexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.


Quality and continuity of information between primary care physicians and rheumatologists.
Good communication is central to a high-quality consultation process. We assessed the quality of referral information from primary care physicians (PCPs) to rheumatologists and the quality and timeliness of consultation letters from rheumatologists back to PCPs. We sampled referral letters between 2000 and 2013 from 168 PCPs and performed a retrospective chart review of 2430 patients referred to 146 rheumatologists. We assessed the completeness and timeliness of referral and consultation letters. Osteoarthritis (n = 787, 32%) and systemic inflammatory rheumatic diseases (n = 745, 31%) comprised the top reasons for referral. Only 55% of referral letters summarized the patients' medical history. Referral letters provided some details of diagnostic tests (51% labs, 34% imaging) but there was underreporting of this information on referral letters. Almost all referral letters (92%) contained details of at least one patient symptom, with the most common complaint being joint pain (54%). Only half of all referral letters provided symptom duration. The PCP only stressed an urgent consultation among 211 patients (9%). Overall, 69% of consultation letters were returned to PCPs within 30 days of consultation visit. We found that basic items necessary for appropriate triage, including a description of symptoms or other relevant history and results of investigations were often lacking in referral letters. The delay of receipt of consultation letters may further represent a lost opportunity for coordination and continuity of care, and may affect the quality of care patients receive.


Antibiotic and antithromboembolic prophylaxis in hip arthroplasty (a review of 700 primary implants).
The authors report the results obtained with antibiotic and antithromboembolic prophylaxis used in 700 consecutive primary total hip arthroplasties. As for antibiotic prophylaxis (5 cases of infection: 0.7%) the various types of antibiotic used always kept the infection rate under 1%, confirming the effectiveness of the preventive use of antibioticotherapy. The incidence of deep venous thrombosis and pulmonary embolia were 3.7% and 0.7%, respectively (26 cases of DVT and 5 of PET). The incidence of DVT rose to 34.4% in a selected group of cases in which phlebography had been carried out even in the absence of symptoms of DVT. This confirms that the routine use of this method would without a doubt be useful in preventing complications with a high risk for the life of the patient (pulmonary embolia). As for pharmacological prophylaxis, indobufene and calcium heparin were the drugs used most: their effectiveness was nearly similar, despite the fact that the use of calcium heparin in patients considered to be at a higher risk for thromboembolic complications should be made clear.


Laparoscopic anterior resection for rectal cancer in a patient with a ventriculoperitoneal shunt.
Laparoscopic surgery has been relatively contraindicated in patients with ventriculoperitoneal shunts (VPS) because of concerns about the effect of the pneumoperitoneum on shunt function. However, there have been recent reports of laparoscopic surgery on the gallbladder and cecum. This is the first report of laparoscopic high anterior resection for rectal cancer without manipulation of the VPS catheter in a patient with VPS. We made a diagnosis of advanced rectal cancer in a 77-year-old man who had a VPS to treat hydrocephalus after a subarachnoid hemorrhage. We performed the procedure with the patient in a 15° head-down tilt and with 10-mmHg pneumoperitoneum pressure. There were no postoperative complications. We concluded that laparoscopic surgery for rectal cancer can be safely performed in patients with VPS.


Adherence to treatment in patient with severe cancer pain: A qualitative enquiry through illness narratives.
Pain is a common symptom in cancer patients and often the most tangible sign of disease they and their families perceive. Despite currently available treatments, cancer pain frequently remains underrated and undertreated because of lack of adherence to the prescribed drug regimen. With this study we sought to identify elements that could facilitate pain management by exploring through narrative interviews the lived experiences of patients with severe chronic cancer pain in relation to their adherence to pain therapy. A purposive sample of 18 cancer patients, treated at the Centre for Oncology and Haematology (COES), City Hospital for Health and Science, Turin, were interviewed. The interview contents were analysed using a qualitative phenomenological methodology as described by Giorgi. Three themes emerged from analysis of the interview transcripts: the significance of pain in subjective experience; the experience of being a patient pursuing a care pathway and the importance attributed to pain therapy. Factors facilitating adherence included the perception of the physical and psychological benefits of having and following a pain medications plan, subjective self-efficacy in pain control, and trust in the healthcare team. Barriers to adherence were negative attitudes toward opioid analgesic therapy, debilitating drug side effects, and denial of pain as a tangible sign of disease. Probing into the significance of the pain experience and its treatment through these narrative interviews revealed several core constituents of adherence. Healthcare providers can use this better understanding to build a trusting relationship with patients and foster adherence to treatment throughout the care pathway.


Results of two worldwide surveys into physician awareness and perceptions of extended-spectrum beta-lactamases.
An omnibus survey of microbiologists (n = 400) and a survey of participants (n = 49) in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme were conducted to determine the awareness and prevalence of extended-spectrum beta-lactamases (ESBLs), and the regularity and method of screening. Of the omnibus survey participants, 69% screened regularly for ESBLs, compared with 83% of MYSTIC participants. In both surveys, ESBLs were more common in Klebsiella pneumoniae (73% and 79%, respectively) and Escherichia coli (63% and 81%, respectively) than in other bacteria. The surveys demonstrated that awareness of, and testing for, ESBLs is inconsistent.


Comprehensive investigation of self-assembled monolayer formation on ferromagnetic thin film surfaces.
We report a simple, universal method for forming high surface coverage SAMs on ferromagnetic thin (< or =100 nm) films of Ni, Co, and Fe. Unlike previous reports, our technique is broadly applicable to different types of SAMs and surface types. Our data constitutes the first comprehensive examination of SAM formation on three different ferromagnetic surface types using two different surface-binding chemistries (thiol and isocyanide) under three different preparation conditions: (1) SAM formation on electroreduced films using a newly developed electroreduction approach, (2) SAM formation on freshly evaporated surfaces in the glovebox, and (3) SAM formation on films exposed to atmospheric conditions beforehand. The extent of SAM formation for all three conditions was probed by cyclic voltammetry for surfaces functionalized with either (11-thiolundecyl)ferrocene (Fc-(CH2) 11-SH) or (11-isocyanoundecyl)ferrocene (Fc-(CH2) 11-NC). SAM formation was also probed for straight-chain molecules, hexadecanethiol and hexadecaneisocyanide, with contact angle measurements, X-ray photoelectron spectroscopy, and reflection-absorption infrared spectroscopy (RAIRS). The results show that high surface coverage SAMs with low surface-oxide content can be achieved for thin, evaporated Ni and Co films using our electroreduction process with thiols. The extent of SAM formation on electroreduced films is comparable to what has been observed for SAMs/Au and to what we observe for SAMs/Ni, Co, and Fe samples prepared in the glovebox.


Train accident victims in Johannesburg. A survey of patients at Baragwanath Hospital, November 1979 to April 1980.
A survey has been carried out on injuries resulting from railway accidents in the Johannesburg district. The train injury was often associated with violent personal assault. The nature of injuries was varied, but there was a high incidence of amputated or crushed limbs and a relatively high incidence of injury to more than one limb.


Evaluation of renin and angiotensin II levels in pseudoexfoliation syndrome.
Pseudoexfoliation syndrome has been linked to impaired function of the heart and blood vessels. We conducted a study to investigate the role of the renin-angiotensin system in the etiopathogenesis of pseudoexfoliation syndrome. The subjects were 14 patients with pseudoexfoliation syndrome and 14 healthy controls who underwent cataract extraction. Preoperative 5-ml samples of peripheral venous blood and perioperative aqueous humor were collected from the patients in both groups. Plasma and aqueous humor renin levels were analyzed by an immunoradiometric method, and angiotensin II levels were analyzed by radioimmunassay. SPSS version 16.0 was used for statistical analyses. A p-value <0.05 was considered to indicate a statistically significant difference. The mean ages of the patients in pseudoexfoliation and control groups were 71.7 ± 7.1 and 67.4 ± 9.3 years, respectively (p=0.140). The median aqueous humor renin level was 7.73 pg/ml (4.15-21) in the control group and 11.95 pg/ml (3.75-18.54) in pseudoexfoliation group (p=0.022). There were no differences between the two groups in the plasma renin, plasma angiotensin II, or aqueous humor angiotensin II levels. The correlations between plasma and aqueous humor renin levels and between plasma and aqueous humor angiotensin II levels were examined separately for each group; no significant correlations were observed in pseudoexfoliation group (r=-0.440, p=0.115; r=-0.414, p=0.142) or the control group (r=-0.232, p=0.425; r=0.482, p=0.081). Aqueous humor renin levels are higher in pseudoexfoliation syndrome. The results indicate a probable role of renin-angiotensin system in pseudoexfoliation syndrome. Further studies with larger numbers of cases are needed to clarify the precise association of renin-angiotensin system with the etiopathogenesis of pseudoexfoliation syndrome.


A comparison of experience-dependent locomotory behaviors and biogenic amine neurons in nematode relatives of Caenorhabditis elegans.
Survival of an animal depends on its ability to match its responses to environmental conditions. To generate an optimal behavioral output, the nervous system must process sensory information and generate a directed motor output in response to stimuli. The nervous system should also store information about experiences to use in the future. The diverse group of free-living nematodes provides an excellent system to study macro- and microevolution of molecular, morphological and behavioral character states associated with such nervous system function. We asked whether an adaptive behavior would vary among bacterivorous nematodes and whether differences in the neurotransmitter systems known to regulate the behavior in one species would reflect differences seen in the adaptive behavior among those species. Caenorhabditis elegans worms slow in the presence of food; this 'basal' slowing is triggered by dopaminergic mechanosensory neurons that detect bacteria. Starved worms slow more dramatically; this 'enhanced' slowing is regulated by serotonin. We examined seven nematode species with known phylogenetic relationship to C. elegans for locomotory behaviors modulated by food (E. coli), and by the worm's recent history of feeding (being well-fed or starved). We found that locomotory behavior in some species was modulated by food and recent feeding experience in a manner similar to C. elegans, but not all the species tested exhibited these food-modulated behaviors. We also found that some worms had different responses to bacteria other than E. coli. Using histochemical and immunological staining, we found that dopaminergic neurons were very similar among all species. For instance, we saw likely homologs of four bilateral pairs of dopaminergic cephalic and deirid neurons known from C. elegans in all seven species examined. In contrast, there was greater variation in the patterns of serotonergic neurons. The presence of presumptive homologs of dopaminergic and serotonergic neurons in a given species did not correlate with the observed differences in locomotory behaviors. This study demonstrates that behaviors can differ significantly between species that appear morphologically very similar, and therefore it is important to consider factors, such as ecology of a species in the wild, when formulating hypotheses about the adaptive significance of a behavior. Our results suggest that evolutionary changes in locomotory behaviors are less likely to be caused by changes in neurotransmitter expression of neurons. Such changes could be caused either by subtle changes in neural circuitry or in the function of the signal transduction pathways mediating these behaviors.


Potentiation of adrenaline-induced platelet aggregation by angiotensin II.
The effects of angiotensin II (ANG II) alone and in combination with other agonists on human platelet aggregation, thromboxane B2 (TxB2) and cytosolic [Ca2+]i were investigated. ANG II (10(-11) - 10(-7) M) alone had no direct effect on aggregation, TxB2 production or [Ca2+]i after short- (less than 2 min) or long-term (30 min) incubation. In contrast, low concentrations of ANG II (10(-11) M) enhanced adrenaline-induced platelet aggregation but high concentrations (10(-7) M) had an inhibitory effect. Moreover, ANG II (10(-11) - 10(-7) M) augmented platelet responses to the TxA2 mimetic, U44069. Pretreatment of platelets with flurbiprofen abolished this facilitatory effect of ANG II on adrenaline- but not on U44069-induced platelet aggregation. These results suggest that ANG II stimulation of agonist-induced platelet activation may be due to potentiation of the effects rather than the synthesis of TxA2.


Porcine circovirus type 2 morphogenesis in a clone derived from the l35 lymphoblastoid cell line.
Porcine circovirus type 2 (PCV2) is the essential infectious agent of post-weaning multisystemic wasting syndrome (PMWS), one of the most important diseases of swine. Although several studies have described different biological properties of the virus, some aspects of its replication cycle, including ultrastructural alterations, remain unknown. The aim of the present study was to describe for the first time a complete morphogenesis study of PCV2 in a clone of the lymphoblastoid L35 cell line at the ultrastructural level using electron microscopy techniques. Cells were infected with PCV2 at a multiplicity of infection of 10 and examined at 0, 6, 12, 24, 48, 60 and 72h post-infection. PCV2 was internalized by endocytosis, after which the virus aggregated in intracytoplasmic inclusion bodies (ICIs). Subsequently, PCV2 was closely associated with mitochondria, completing a first cytoplasmic phase. The virus entered the nucleus for replication and virus assembly and encapsidation occurred with the participation of the nuclear membrane. Immature virions left the nucleus and formed ICIs in a second cytoplasmic phase. The results suggest that at the end of the replication cycle (between 24 and 48h), PCV2 was released either by budding of mature virion clusters or by lysis of apoptotic or dead cells. In conclusion, the L35-derived clone represents a suitable in-vitro model for PCV2 morphogenesis studies and characterization of the PCV2 replication cycle.