Studies of the retinal microcirculation using human donor eyes and high-resolution clinical imaging: Insights gained to guide future research in diabetic retinopathy.
The microcirculation plays a key role in delivering oxygen to and removing metabolic wastes from energy-intensive retinal neurons. Microvascular changes are a hallmark feature of diabetic retinopathy (DR), a major cause of irreversible vision loss globally. Early investigators have performed landmark studies characterising the pathologic manifestations of DR. Previous works have collectively informed us of the clinical stages of DR and the retinal manifestations associated with devastating vision loss. Since these reports, major advancements in histologic techniques coupled with three-dimensional image processing has facilitated a deeper understanding of the structural characteristics in the healthy and diseased retinal circulation. Furthermore, breakthroughs in high-resolution retinal imaging have facilitated clinical translation of histologic knowledge to detect and monitor progression of microcirculatory disturbances with greater precision. Isolated perfusion techniques have been applied to human donor eyes to further our understanding of the cytoarchitectural characteristics of the normal human retinal circulation as well as provide novel insights into the pathophysiology of DR. Histology has been used to validate emerging in vivo retinal imaging techniques such as optical coherence tomography angiography. This report provides an overview of our research on the human retinal microcirculation in the context of the current ophthalmic literature. We commence by proposing a standardised histologic lexicon for characterising the human retinal microcirculation and subsequently discuss the pathophysiologic mechanisms underlying key manifestations of DR, with a focus on microaneurysms and retinal ischaemia. The advantages and limitations of current retinal imaging modalities as determined using histologic validation are also presented. We conclude with an overview of the implications of our research and provide a perspective on future directions in DR research.


Tracheal double-lumen ventilation attenuates hypercapnia and respiratory acidosis in lung injured pigs.
Evaluation of ventilatory and circulatory effects with coaxial double-lumen tube ventilation for dead-space reduction as compared with standard endotracheal tube ventilation. Experimental study in a pig model of lung lavage induced acute lung injury. University research laboratory. Tidal volumes of 6, 8 and 10 ml/kg body weight with a set respiratory rate of 20 breaths per minute were used in a random order with both double-lumen ventilation and standard endotracheal tube ventilation. Measurements of ventilatory and circulatory parameters were obtained after steady state at each experimental stage. With a tidal volume of 6 ml/kg, PaCO(2) was reduced from 10.9 kPa (95% CI 9.0-12.9) with a standard endotracheal tube to 8.2 kPa (95% CI 7.0-9.4) with double-lumen ventilation. This corresponds to a reduction in carbon dioxide levels by 25%. At 6 ml/kg, pH increased from 7.17 (95% CI 7.09-7.24) with a standard endotracheal tube to 7.27 (95% CI 7.21-7.32) with double-lumen ventilation. Tracheal pressure was monitored continuously and no difference between single- or double-lumen ventilation was noted at corresponding levels of ventilation. There was no formation of auto-PEEP. Partial tube obstruction due to secretions was not observed during the experiments. Coaxial double-lumen tube ventilation is an effective adjunct to reduce technical dead space. It attenuates hypercapnia and respiratory acidosis in a lung injury pig model.


Customized transapical thoracic endovascular repair for acute type A dissection.
A 67-year-old patient with severe comorbidities and acute type A aortic dissection with pericardial tamponade was treated with an endograft introduced through a mini-thoracotomy and puncture of the left ventricular apex. Final angiography showed complete coverage of the dissection. Early and 6-month follow-up computed tomography showed full apposition of the endograft without residual dissection. Transapical thoracic endovascular repair of acute type A aortic dissection appears to be feasible and is associated with minimal physiologic compromise. It may provide a less invasive alternative for patients with increased operative mortality.


The drug lag: an update of new drug introductions in the United States and in the United Kingdom, 1977 through 1987.
This report updates previous studies that documented the existence of a significant lag between new drug introductions in the United Kingdom and in the United States. During the 11-year period from 1977 through 1987, the United Kingdom led the United States in the number of first introductions of new drugs (114 versus 41), in average lead time for mutually available drugs (60.7 versus 28.9 months), and in the number of exclusively available drugs (70 versus 54). Analysis by therapeutic category indicated large United Kingdom leads in the introduction of respiratory (5.1 years), cardiovascular (3.2 years), central nervous system (3.2 years), and anti-cancer (2.9 years) agents, and shorter leads for anesthetic and analgesic (2.0 years), gastrointestinal (2.0 years), endocrine (1.4 years), and anti-infective (0.8 years) agents. A comparison of the 5-year period from 1983 through 1987 with the previous 5-year period (1978 through 1982) showed no change in the length of the lag time (1.9 years for each period). These results indicate that the United States continues to lag behind the United Kingdom in the availability of new drugs.


Global, regional, and national trends in mesothelioma burden from 1990 to 2019 and the predictions for the next two decades.
We aimed to analyze the secular trends in mesothelioma burden, the effect of age, period, and birth cohort, and project the global burden over time. Based on the mesothelioma incidence, mortality, and Disability-Adjusted Life Years (DALYs) data from 1990 to 2019 in Global Burden of Diseases (GBD) database, the annual percentage change (APC) and average annual percent change (AAPC), calculated from joinpoint regression model, was used to describe the burden trends. An age-period-cohort model was utilized to disentangle age, period, and birth cohort effects on mesothelioma incidence and mortality trends. The mesothelioma burden was projected by the Bayesian age-period-cohort (BAPC) model. Globally, there were the significant declines in age-standardized incidence rate (ASIR) (AAPC = -0.4, 95%CI: -0.6,-0.3, P < 0.001), age-standardized mortality rate (ASMR) (AAPC = -0.3, 95%CI: -0.4,-0.2, P < 0.001), and age-standardized DALY rate (ASDR) (AAPC = -0.5, 95%CI: -0.6,-0.4, P < 0.001) of mesothelioma overall 30 years. For regions, Central Europe presented the most distinct increases and the most substantial decrease was observed in Andean Latin America on all ASRs (age-standardized rates) from 1990 to 2019. At national level, the largest annualized growth for full-range trends of incidence, mortality, and DALYs was in Georgia. Conversely, the fastest descent of all ASRs was observed in Peru. The ASIR, ASMR, and ASDR in 2039 predicted 0.33, 0.27, and 6.90 per 100,000, respectively. The global burden of mesothelioma declined over the past 30 years, with variability across regions and countries/territories, and this trend will continue in the future.


Abundant Aβ fibrils in ultracentrifugal supernatants of aqueous extracts from Alzheimer's disease brains.
Soluble oligomers of amyloid β-protein (Aβ) have been defined as aggregates in supernatants following ultracentrifugation of aqueous extracts from Alzheimer's disease (AD) brains and are believed to be upstream initiators of synaptic dysfunction, but little is known about their structures. We now report the unexpected presence of Aβ fibrils in synaptotoxic high-speed supernatants from AD brains extracted by soaking in an aqueous buffer. The fibrils did not appear to form during preparation, and their counts by EM correlated with Aβ ELISA quantification. Cryo-EM structures of aqueous Aβ fibrils were identical to those from sarkosyl-insoluble homogenates. The fibrils in aqueous extracts were labeled by lecanemab, an Aβ aggregate-directed antibody reported to improve AD cognitive outcomes. Lecanemab provided protection against aqueous fibril synaptotoxicity. We conclude that fibrils are abundant in aqueous extracts from AD brains and have the same structures as those from plaques. These findings have implications for AD pathogenesis and drug design.


Native plants for the remediation of abandoned sulphide mines in Cyprus: A preliminary assessment.
Mining in Cyprus resulted in a significant number of abandoned sulphide mines without any rehabilitation measures. The present study aims to describe and compare the environmental parameters in three such mines with respect to water chemistry, waste dumps geochemistry, slope-topography and plant growth. The mines under study are that of Kokkinopezoula, North and South Mathiatis located at the northeast of the Troodos massif. A synopsis of the previous studies conducted for the above-mentioned mines is presented, which includes water and soil samples analyses. Although, in these areas environmental degradation is reported, there are some plants which grow naturally. Therefore, a preliminary attempt to report these plants is conducted, while remediation options presented in the literature including technosols, revegetation, phytoremediation and phytostabilization are proposed. Potential use of native plants such as Phragmites australis, Tamarix smyrnensis, Poaceae, Pinus brutia and Schoenus nigricans Poaceace could be applied for phytoremediation of the sulphide mines in Cyprus. These plants seem to have great strength at low pH values and high metal content in contaminated soils and water. The three mines under study are also compared with three other old mines located in the broader area of Cyprus; that of Xeros, Limni and Skouriotissa, which operated under similar climatic conditions. By improving abandoned mines environment with technosols, the action of native plants will be enhanced and thus work towards a successful phytoremediation treatment, resulting in the minimization of future pollutants generated by the solid waste dumps.


Evaluating intense rehabilitative therapies with and without acupuncture for children with cerebral palsy: a randomized controlled trial.
To compare the outcomes of conventional therapies (physical, occupational, and hydrotherapies) plus acupuncture with those without acupuncture when administered intensely in the management of children with spastic cerebral palsy (CP). Evaluation-blind, prospective randomized controlled trial. Therapies and video-recorded assessments at a children's hospital in Beijing, China, and blind scoring and data analyses at a university in the United States. Children (N=75), 12 to 72 months of age, with spastic CP. Intensely administered (5 times per week for 12wk) physical therapy, occupational therapy, and hydrotherapy either with acupuncture (group 1) or without acupuncture (group 2). To satisfy standard of care, group 2 subsequently received acupuncture (weeks 16-28). The Gross Motor Function Measure (GMFM)-66 and the Pediatric Evaluation of Disability Inventory (PEDI) assessments at 0, 4, 8, 12, 16, and 28 weeks. At the end of 12 weeks, there was no statistically significant difference between the 2 groups, but when group 2 received acupuncture (16-28wk) there was a shift toward improvement in the GMFM-66 and the PEDI-Functional Skills Self-Care and Mobility domain. When groups were combined, statistically significant improvements after intense therapies occurred from baseline to 12 weeks for each outcome measure at each Gross Motor Function Classification System (GMFCS) level. After adjusting for expected normative maturational gains based on age, the GMFM gains for children with GMFCS II level was statistically significant (P<.05) with a mean gain of 6.5 versus a predicted gain of 3.4. Intense early administered rehabilitation improves function in children with spastic CP. The contribution from acupuncture was unclear. Children's response varied widely, suggesting the importance of defining clinical profiles that identify which children might benefit most. Further research should explore how this approach might apply in the U.S.


Relative importance of host plant patch geometry and habitat quality on the patterns of occupancy, extinction and density of the monophagous butterfly Iolana iolas.
Habitat fragmentation is a major cause of species rarity and decline because it increases local population extinctions and reduces recolonisation rates of remnant patches. Although two major patch characteristics (area and connectivity) have been used to predict distribution patterns in fragmented landscapes, other factors can affect the occurrence of a species as well as the probability of it becoming extinct. In this paper, we study the spatial structure and dynamics of the butterfly Iolana iolas in a 75-patch network of its host plant (Colutea hispanica) to determine the relative importance of patch area, connectivity and habitat quality characteristics on occupancy, extinction and density over the period 2003-2006. Occupancy in 2003, incidence (proportion of years occupied) and probability of extinction were mostly affected by patch area. Smaller patches were less likely to be occupied because they had a higher probability of extinction, partly due to environmental stochasticity. The density of I. iolas was negatively related to patch area in all study years. Only in 2004 was the density of I. iolas positively influenced by fruit production per plant. Our results suggest that for I. iolas, and probably for other specialist butterflies with clearly delimited resource requirements, metapopulation dynamics can be satisfactorily predicted using only geometric variables because most habitat characteristics are subsumed in patch area. However, this hypothesis should be subject to further testing under diverse environmental conditions to evaluate the extent of its generalisation.


Soft tissue knee contracture of the knee due to melorheostosis, treated by total knee arthroplasty.
Melorheostosis is a rare condition which can cause soft tissue joint contractures. We present a case of melorheostosis causing disabling knee joint contracture, treated successfully by total knee arthroplasty.


Detection of CD55- and/or CD59-deficient red cell populations in patients with plasma cell dyscrasias.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder characterized by a decrease or absence of glycosylphosphatidylinositol (GPI)-anchored molecules such as CD55 and CD59 from the surface of affected cells, resulting in intravascular hemolysis, cytopenia, and venous thrombosis. A PNH-like phenotype has been detected in various hematological disorders, mainly in aplastic anemia and myelodysplastic syndromes, but also in lymphoproliferative syndromes (LPSs). To the best of our knowledge, CD55- or CD59-deficient red cells have not been detected in plasma cell dyscrasias (PCDs). The aim of this study was the detection of CD55- and/or CD59-deficient red cell populations in patients with PCD. Seventy-seven patients were evaluated; 62 with multiple myeloma (MM), 7 with Waldenstrom macroglobulinemia (WM), 6 with monoclonal gammopathy of undetermined significance (MGUS), and 2 with heavy chain disease (HCD). The sephacryl gel microtyping system was applied; Ham and sucrose lysis tests were also performed on all samples with CD55- or CD59-negative populations. Red cells deficient in both molecules were detected in 10 (12.9%) of 77 patients with PCD: 2 (28.6%) of 7 with WM, 1 (16.6%) of 6 with MGUS, 6 (9.6%) of 62 with MM, and 1 of 2 patients with HCD. Isolated CD55 deficiency was found in 28.5% of all PCD patients, whereas isolated CD59 deficiency was not observed in any patients. These findings illustrate the existence of the PNH phenotype in the red cells of patients with PCD; further investigation is needed into the mechanisms and significance of this phenotype.


Research methodology. Part I: Understanding correlational analysis.
This paper is part one of a four part series on basic statistical analytical methods. Using a case method presentation, the basic essentials of correlational analysis is described.


ABACUS, a direct method for protein NMR structure computation via assembly of fragments.
The ABACUS algorithm obtains the protein NMR structure from unassigned NOESY distance restraints. ABACUS works as an integrated approach that uses the complete set of available NMR experimental information in parallel and yields spin system typing, NOE spin pair identities, sequence specific resonance assignments, and protein structure, all at once. The protocol starts from unassigned molecular fragments (including single amino acid spin systems) derived from triple-resonance (1)H/(13)C/(15)N NMR experiments. Identifications of connected spin systems and NOEs precede the full sequence specific resonance assignments. The latter are obtained iteratively via Monte Carlo-Metropolis and/or probabilistic sequence selections, molecular dynamics structure computation and BACUS filtering (A. Grishaev and M. Llinás, J Biomol NMR 2004;28:1-10). ABACUS starts from scratch, without the requirement of an initial approximate structure, and improves iteratively the NOE identities in a self-consistent fashion. The procedure was run as a blind test on data recorded on mth1743, a 70-amino acid genomic protein from M. thermoautotrophicum. It converges to a structure in ca. 15 cycles of computation on a 3-GHz processor PC. The calculated structures are very similar to the ones obtained via conventional methods (1.22 A backbone RMSD). The success of ABACUS on mth1743 further validates BACUS as a NOESY identification protocol.


ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins.
ScanProsite--http://www.expasy.org/tools/scanprosite/--is a new and improved version of the web-based tool for detecting PROSITE signature matches in protein sequences. For a number of PROSITE profiles, the tool now makes use of ProRules--context-dependent annotation templates--to detect functional and structural intra-domain residues. The detection of those features enhances the power of function prediction based on profiles. Both user-defined sequences and sequences from the UniProt Knowledgebase can be matched against custom patterns, or against PROSITE signatures. To improve response times, matches of sequences from UniProtKB against PROSITE signatures are now retrieved from a pre-computed match database. Several output modes are available including simple text views and a rich mode providing an interactive match and feature viewer with a graphical representation of results.


Study of the competitive isotherm model and the mass transfer kinetics for a BET binary system.
The competitive adsorption behavior of the binary mixture of phenetole (ethoxy-benzene) and propyl benzoate in a reversed-phase system was investigated. The adsorption equilibrium data of the single-component systems were acquired by frontal analysis. The same data for binary mixtures were acquired by the perturbation method. For both compounds, the single-component isotherm data fit best to the multilayer BET model. The experimental overloaded band profiles are in excellent agreement with the profiles calculated with either the general rate model or the modified transport-dispersive models. The competitive adsorption data were modeled using the ideal adsorbed solution (IAS) theory. The numerical values of the coefficients were derived by fitting the retention times of the perturbation pulses to those calculated using the IAS theory compiled with the coherence conditions. Finally, the elution profiles of binary mixtures were recorded. They compared very well with those calculated. As a characteristic feature of this case, an unusual retainment effect of the chromatographic band of the more retained component by the less retained one was observed. The combination of the General Rate Model and the adsorption isotherm model allowed an accurate prediction of the band profiles.


Survival and prognostic factors of women with advanced ovarian cancer and complete response after a carboplatin-paclitaxel chemotherapy.
We evaluated the characteristics and determinants of 5-year survival in ovarian cancer patients with complete response after first line treatment who entered a randomised study comparing two different chemotherapeutic schedules. This analysis included 232 ovarian cancer patients with complete response after first line surgery and chemotherapy coming from a large randomised trial comparing the effect of different doses of paclitaxel combined with fixed doses of carboplatin. The 5-year overall survival in patients was 57.3%. The difference in 5-year survival for age <52 years (65.1%), 53-62 (51.4%) and > or = 63 (51.2%) was statistically significant (P = 0.048). The 5-year overall survival rates were 64.6% for stage III and 57.9% for stage IV. Serous and clear cell histotypes had a worse 5-year overall survival (51.5% and 50.8% respectively), while the endometrioid and mucinous had 67.1% and 71.4%: these differences were statistically different (P = 0.04). Women with residual tumour of 1 cm or smaller after primary surgery had better 5-year survival rates: 71.2% for patients with residual tumour < or = 1 cm and 46.9% for residual tumour >1 cm: these differences were statistically significant (P < 0.006). This study shows that in women with ovarian cancer and complete response after first line surgery and chemotherapy, age, histotype and residual tumour after surgery are determinants of 5-year overall survival.


SUMO-1 modification of centrosomal protein hNinein promotes hNinein nuclear localization.
A centrosomal-associated protein, ninein is a microtubules minus end capping, centrosome position, and anchoring protein, but the underlying structure and physiological functions are still unknown. To identify the molecules that regulate the function of human ninein in centrosome, we performed yeast two-hybrid screen and isolated the SUMO-conjugating E2 enzyme, Ubc9, and SUMOylation enhancing enzymes, including PIAS1 and PIASxalpha, as binding partners of hNinein. These interactions as well as the interaction between hNinein and SUMO-1 are also confirmed by a glutathione S-transferase (GST) pull-down experiment. Furthermore, the C-terminal region of hNinein can be SUMOylated in vitro and in HeLa cells transfected with a plasmid expressing GFP-hNinein. Our findings firstly place SUMOylation target on the centrosome structure protein, hNinein, which results in the switch localization from centrosome to nucleus, suggesting the importance of the SUMOylation of hNinein and probably other centrosomal proteins may also be involved in the centrosome activity.


Use of stable 48Ca in the clinical measurement of intestinal calcium absorption.
Measurements of intestinal-calcium-absorption efficiency are fundamental for understanding calcium homeostasis in health and disease. Stable calcium isotopes are attractive tracers for such measurements, to avoid excessive radiation exposure to the subject and permit serial studies at short intervals. To realize this, we found it necessary to improve the sensitivity and precision of existing thermal neutron activation analyses for 48Ca. This report describes the details, sensitivity, precision, and accuracy of the improved method, and gives the results of studies in which intravenous 48Ca was used in conjunction with oral 47Ca to measure intestinal-calcium-absorption efficiency in patients.


Lanthanide luminescent displacement assays: the sensing of phosphate anions using Eu(III)-cyclen-conjugated gold nanoparticles in aqueous solution.
1.Eu, a cyclen based Eu(III)-thiol conjugate, was incorporated onto the surface of water-soluble gold nanoparticles to give AuNP-1.Eu. The self-assembly between AuNP-1.Eu and the antenna 2 resulted in the formation of the highly luminescent lanthanide system, AuNP-1.Eu-2, at pH 7.4. The sensing of flavin monophosphate 3 is demonstrated, whereby 3 displaced the antenna 2 in AuNP-1.Eu-2, resulting in the formation of AuNP-1.Eu-3 and quenching of the Eu(III) emission.


Laparoscopic pyeloplasty: the first 100 cases.
Laparoscopic pyeloplasty was developed as a minimally invasive alternative to an open procedure for the treatment of ureteropelvic junction obstruction. Long-term followup has not yet been reported. We present experience with the first 100 consecutive cases of laparoscopic pyeloplasty performed at our institution. A retrospective review of 100 consecutive laparoscopic pyeloplasties in 99 patients (means age 37.3 years) between August 1993 and January 1999 was performed. All patients had radiographic evidence of obstruction with signs, symptoms or deterioration of renal function. Repair was for primary ureteropelvic junction obstruction in 83 patients and secondary obstruction in 17. The 4 types of repairs performed were Anderson-Hynes dismembered (71 cases), Y-V plasty (20), Heineke-Mirhulicz (8) and Davis intubated ureterotomy (1). Type of repair used was dictated by intraoperative findings. Twenty patients had nonobstructing renal stones and underwent concomitant pyelolithotomy. All patients were assessed for symptoms and radiographic evaluation for anatomical obstruction. Average operating room time was 4.2 hours, which decreased with surgeon experience. Average blood loss was 181 cc and hospital stay was 3.3 days. Two patients required blood transfusion. A crossing vessel was found in 57 patients. With a mean clinical and radiographic followup of 2.7 and 2.2 years, respectively, 96% of the patients were free of obstruction on followup radiographic imaging. Of the patients who underwent concomitant pyelolithotomy, 18 (90%) were stone-free at last followup. All failures occurred within the first postoperative year. There were 12 complications in this series. In experienced hands laparoscopic pyeloplasty is an effective alternative treatment for symptomatic ureteropelvic junction obstruction. The results appear durable and comparable to open pyeloplasty with decreased postoperative morbidity.


Dibucaine number (DN) in duodenal ulcer.
Dibucaine Number (DN) was determined in 103 patients suffering from duodenal ulcer diagnosed radiologically and 214 normal subjects (control). Statistically significant (p less than 0.001) difference was observed in the distribution of DN in the two groups. Whereas 94% of the control subjects had normal DN (above 70), 6% had intermediate DN (between 40--70) and none had atypical DN, only 32% of patients suffering from duodenal ulcer had normal DN, 64% had intermediate DN and 4% had atypical DN. The results have been discussed.


Examining environmental friendly behaviors of tourists towards sustainable development.
This study investigated the tourists' novel intentions to save environment and what parameters impact their pro-environment decisions. Structural Equation Modeling was used to test the integrated study model to get correct and unbiased path coefficients with the help of 227 responses. The study results revealed that greater the environmental knowledge of environmental friendly products, the more positive attitude towards environmental friendly products was perceived and international tourists perceived it significantly high in comparison to domestic tourists Interestingly Control on Availability didn't impact purchase intentions of tourists in the current study, a finding different from literature across other contexts. Attitude didn't have significant mediating effect in the relationship between environmental knowledge and purchase intentions. On the other hand, purchase intentions positively influenced purchase behavior of tourists. Practical implications are discussed at large.


Changes in membrane properties of erythrocytes and polymorphonuclear cells in psoriasis.
Using fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene and its cationic derivative, 1-(4-trimethylaminophenyl)-6-phenyl-1,3,5-hexatriene, we evaluated membrane fluidity in living polymorphonuclear leukocytes and in erythrocytes of psoriatic patients. Our results have shown that erythrocyte membranes of psoriatic patients exhibit a decrease of fluidity. These changes were not associated with any relevant modifications of the cholesterol to phospholipid molar ratio. Moreover, we observed a decrease in polymorphonuclear leukocytes membrane fluidity associated with changes in chemotactic migration. Our results indicate changes of membrane fluidity involving membranes different from the epidermal cells and suggest the hypothesis of a defective membrane-cytoskeleton interaction in psoriasis.


Juvenile hormone binding by components of fat body cytosol from vitellogenic locusts.
Binding of 3H-labeled juvenile hormone (JH) to cytosol components of fat body from adult female Locusta migratoria, a tissue in which JH stimulates vitellogenin synthesis, has been characterized. Protein-bound JH is separated from unbound hormone with hydroxyapatite, which is found to provide a more sensitive and less variable assay than use of dextran-coated charcoal. By chromatography on DEAE-cellulose, three JH-binding components have been separated from cytosol. BP-I exhibited relatively stable binding with little degradation of the hormone, gave a Kd for JH-I by Scatchard analysis of 1.69 X 10(-8) M, and binding of JH-I was competed by JH-I and several synthetic JH analogs in an order corresponding to their JH activities. These characteristics suggest that BP-I may be a cytoplasmic JH receptor. BP-II, a minor component, also bound JH-I stably, but competition by analogs was not correlated with their hormone activity. BP-III caused rapid degradation of JH to JH acid and may be an esterase.


Chloride transport in microperfused interlobular ducts isolated from guinea-pig pancreas.
Isolated interlobular ducts from the guinea-pig pancreas secrete a HCO3--rich fluid in response to secretin. To determine the role of Cl- transporters in this process, intracellular Cl- concentration ([Cl-]i) was measured in ducts loaded with the Cl--sensitive fluoroprobe, 6-methoxy-N-ethylquinolinium chloride (MEQ). [Cl-]i decreased when the luminal Cl- concentration was reduced. This effect was stimulated by forskolin, was not dependent on HCO3- and was not inhibited by application of the anion channel/transporter inhibitor H2DIDS to the luminal membrane. It is therefore attributed to a cAMP-stimulated Cl- conductance, probably the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel. [Cl-]i also decreased when the basolateral Cl- concentration was reduced. This effect was not stimulated by forskolin, was largely dependent on HCO3- and was inhibited by basolateral H2DIDS. It is therefore mediated mainly by Cl-/HCO3- exchange. With high Cl- and low HCO3- concentrations in the lumen, steady-state [Cl-]i was 25-35 mM in unstimulated cells. Stimulation with forskolin caused [Cl-]i to increase by approximately 4 mM due to activation of the luminal anion exchanger. With low Cl- and high HCO3- concentrations in the lumen to simulate physiological conditions, steady-state [Cl-]i was 10-15 mM in unstimulated cells. Upon stimulation with forskolin, [Cl-]i fell to approximately 7 mM due to increased Cl- efflux via the luminal conductance. We conclude that, during stimulation under physiological conditions, [Cl-]i decreases to very low levels in guinea-pig pancreatic duct cells, largely as a result of the limited capacity of the basolateral transporters for Cl- uptake. The resulting lack of competition from intracellular Cl- may therefore favour HCO3- secretion via anion conductances in the luminal membrane, possibly CFTR.


Films for eliciting emotional states in children.
Standardized sets of films have been shown to be effective for eliciting emotional states in adults, but no comparable validated stimuli are available for children. We therefore examined the effects of three pre-selected film clips each of 3-min duration in eliciting a pleasant, neutral and unpleasant emotional state in 297 children aged between 6 and 12 years. After the films were presented on a video projector, affective ratings were obtained with the Self-Assessment-Manikin on the emotional dimensions of valence and arousal. Increasing pleasure ratings were observed from the unpleasant to the neutral to the pleasant film. Associated arousal ratings were stronger for the unpleasant and pleasant films compared to the neutral film. Overall, results showed successful elicitation of targeted emotional states only marginally influenced by age, gender or prior experience with the films. The use of these films is therefore suggested for future studies on emotions in children.


Microvascular plug: a new embolic material for hepatic arterial skeletonization.
Arterial skeletonization before radioembolization or hepatic artery port catheter placement for chemotherapy is a crucial step to prevent side effects. Coils are commonly used as an embolic material for hepatoenteric arterial occlusion. Herein is reported for the first time the clinical use of a new detachable microvascular plug (MVP) suitable for occlusion of 1-3 mm diameter vessels. The MVP allows vessel embolization even in challenging anatomy such as the right gastric artery. Furthermore, immediate and stable vessel occlusion was observed in our pilot study of 16 MVP placements.


The Usp8 deubiquitination enzyme is post-translationally modified by tyrosine and serine phosphorylation.
The ERBB1-ERBB4 receptors belong to a family of receptor tyrosine kinases that trigger a network of signaling pathways after ligand binding, thereby regulating cellular growth, differentiation and development. Ligand-induced signaling through ERBB1, also known as EGFR, is attenuated by the clathrin-dependent receptor-mediated endocytosis and RING E3-ligase Cbl-mediated receptor ubiquitination, which is followed by incorporation into multi-vesicular bodies (MVBs) and subsequent degradation in lysosomes. Before incorporation into MVBs, the EGFR is deubiquitinated by Usp8. We previously demonstrated that Usp8 is tyrosine phosphorylated in an EGFR- and SRC-kinase dependent manner. In the present study we show that overexpression of constitutively active SRC enhances constitutive and ligand-induced Usp8 tyrosine phosphorylation. We also show that enhanced endosomal recycling of the EGFR induced by TGFα stimulation is associated with decreased Usp8 tyrosine phosphorylation. We therefore hypothesize that tyrosine phosphorylation of Usp8 could regulate the function of Usp8. To identify Usp8 tyrosine phosphorylation site(s), we used Usp8 deletion constructs, site-directed mutagenesis of nine individual Usp8 tyrosine residues and mass spectrometry (MS) analysis. Our results demonstrate that the MIT-domain is necessary for ligand-induced tyrosine phosphorylation of Usp8 1-504. However, mutation of three MIT domain tyrosine residues did not abolish Usp8 tyrosine phosphorylation. Similar results were obtained upon mutation of six exposed tyrosine residues in the Rhod domain and linker region. Repeated MS analysis of both Usp8 WT and C748A mutants readily detected serine phosphorylation, including the S680 14-3-3 binding site, but did not reveal any phospho-tyrosine residues. Notably, mutation of the tyrosine residue in the Usp8 14-3-3 binding motif (Y679) did not abolish phosphoserine-dependent binding of 14-3-3 to Usp8. Our findings are most consistent with the model that MIT domain-dependent recruitment of Usp8 to endosomal membranes is important for low stoichiometry SRC-mediated tyrosine phosphorylation of multiple Usp8 tyrosines. Our findings demonstrate that Usp8 is a target for the post-translational serine and tyrosine phosphorylation, most likely characterized by low abundant tyrosine phosphorylation on multiple residues, and high abundant serine phosphorylation on several residues.


A topological and functional model of epitopes on the structural glycoprotein of tick-borne encephalitis virus defined by monoclonal antibodies.
A topological and functional model of eight distinct epitopes on the structural glycoprotein of tick-borne encephalitis (TBE) virus was established by the use of monoclonal antibodies. The unique specificities and spatial relationships of these antibodies were determined by variant analysis, haemagglutination inhibition (HI), neutralization, passive mouse protection, and antibody blocking assays. Seven out of the eight distinct epitopes were shown to be partially linked and to cluster in two antigenically reactive domains (A, B). Each of these domains is inhomogeneous and contains constituents with different serological specificities and functions. Domain A is defined by three HA-inhibiting antibodies, two of which are flavivirus group-reactive, whereas the third is TBE virus subtype specific. Within this domain only the subtype-specific antibody is involved in virus neutralization, thus explaining the observation that neutralization tests with flaviviruses show higher serological specificities than HI tests and that HI tests can be made type and subtype specific by antibody absorption. Domain B is composed of three TBE-complex reactive epitopes, and the corresponding antibodies inhibit HA and neutralize the virus. A fourth epitope linked to this domain is neither involved in HA nor in neutralization and the same holds true for a subtype-specific epitope which is topologically independent of domains A and B. Each of two different nonneutralizing antibodies was capable of blocking the binding of distinct neutralizing antibodies. All eight epitopes are indistinguishably present on strains of the western subtype of TBE virus isolated all over Europe in different years from different hosts, thus again confirming the great stability of this virus.


The development of alkaline phosphatase activity in limb buds of mouse embryos in vitro and its relation to chondrogenesis.
The development of alkaline phosphatase (aPh) activity and chondrogenesis were studied in the limb buds of mouse embryos (day 11 p.c.) that had been grown in an organ culture. During a 12-day culture period an increase in aPh activity to more than 40 mU/limb bud was measured from day 2 in vitro onward. Depending on the time of application, aPh formation can be inhibited by certain substances. Cytosine-arabinoside inhibits aPh activity when the substance is added on day 2, 3, or 4. Chondrogenesis, on the other hand, is affected on days 1, 2, and 3 and to a lesser degree on day 4. Actinomycin D interferes with aPh activity after its addition on day 1, 2, 3, or 4. Chondrogenesis is only inhibited when the drug is applied on the 1st, 2nd, or to a lesser degree on the 3rd day. Cycloheximide inhibits aPh formation on all days of treatment, but to a lesser degree on days 5 and 6; chondrogenesis is most influenced on days 2, 3, and 4. On day 6 of the culture period, aPh activity can be demonstrated histochemically only in the region of humerus and proximal parts of radius and ulna. Alterations in the distal cartilage skeleton, therefore, do not influence the activity data. A prerequisite for an increase in aPh activity is cartilage growth in the proximal part of the limb buds and subsequent induction of a perichondral cell population to proliferation and differentiation.


Fluorimetric assay for human intestinal glycine peptidases.
A sensitive but simple fluorimetric assay for intestinal enzymes capable of hydrolysing certain glycine-containing peptides is described. In the standard assay, 1 nanomole of glycine can be accurately estimated in the presence of a 2000-fold molar excess of unhydrolysed peptide. Initial rates of peptide hydrolysis can be measured on the density gradient fractions obtained by analytical subcellular fractionation of extracts from milligram quantities of human jejunal tissue. Differences in the subcellular localisation of activity against two peptides are illustrated. The implications of these findings in relation to the study of intestinal peptidase deficiency in disease states are discussed.


Removal of low-density lipoproteins (LDL) and fibrinogen by precipitation with heparin at low pH: clinical application and experience.
The clinical application of a new extracorporeal procedure (HELP) for the selective elimination of low-density lipoproteins and fibrinogen by heparin precipitation at acid pH is described. Plasma, obtained by filtration of whole blood through a 0.2 micron filter is continuously mixed with an equal volume of an acetate buffer (pH 4.85) containing heparin. After removal of the precipitated heparin complex by filtration, excess heparin is adsorbed to a specially developed filter, and the clear plasma filtrate is subject to bicarbonate dialysis/ultrafiltration to restore physiologic pH and remove excess fluid. The calculated efficiency for the elimination of low-density lipoproteins and fibrinogen from plasma by HELP is 100% and is therefore comparable to conventional plasmapheresis. However, the HELP system shows a high degree of specificity, with over 80% of total protein being returned to the patient. A total of over 350 treatment procedures have now been performed. Patient compliance and acceptance have been excellent, and no major complications have been observed. The system is therefore suitable for the treatment of severe hyper-beta-lipoproteinemia; its use for the treatment of coronary heart disease is currently under investigation in a prospective multicenter study in which treatment efficiency will be controlled by coronary angiography on 45 patients treated with HELP over a period of 2 years.


Heavy metal pollution levels and health risk assessment of dust storms in Jazmurian region, Iran.
The Jazmurian basin in Iran is an area affected by climate change and desertification where aerosols and dust storms are common. The aim of this work was to determine the human and ecological risks from atmospheric particles during dust storms in different cities in the Jazmurian basin. For this purpose, the dust samples were collected from Jiroft, Roodbar Jonoob, Ghaleh Ganj, Kahnooj and Iranshahr cities, which are located around the Jazmurian playa in southeast of Iran. Satellite-based Moderate Resolution Imaging Spectroradiometer (MODIS) aerosol products and the Aerosol Optical Depth (AOD) were used to detect aerosol loading in the atmosphere. Moreover, the trace element composition of the collected particles was determined and used to evaluate human and ecological impact assessment using US EPA human health risk assessment and ReCiPe 2016 endpoint hierarchist impact assessment method incorporated in the OpenLCA 1.10.3 software. The human health risk assessment of the particles revealed high non-carcinogenic risks for children from exposure to nickel and manganese and carcinogenic risks in both adults and children due to hexavalent chromium, arsenic and cobalt during dust storm events. Terrestrial ecotoxicity was found to have the largest ecological impact on ecosystems with copper, nickel and zinc exhibiting the largest contributions.


Hirschsprung disease in the offspring of mothers exposed to hyperthermia during pregnancy.
Interview data for events of pregnancy on 40 infants with Hirschsprung disease showed a significant relationship to a history of hyperthermia in the mother in the first trimester, during the time of embryonic development and migration of ganglion cells along the intestine. In order to eliminate maternal recall bias, a control group consisted of 41 malformed infants with congenital limb deficiency. Hyperthermia may be one factor contributing to the cause of some cases of Hirschsprung disease.


Orbital cellulitis and sinusitis caused by group B beta streptococcus in a 3-year-old child.
This paper reports a case in which an odontogenic infection extended into a maxillary sinus in an otherwise well 3-year-old child. The resulting sinusitis and orbital cellulitis were caused by an organism which does not usually cause disease in this age group, group B β-hemolytic streptococcus.


Role of fluorescein glucuronide and its metabolism in vitreous fluorophotometry.
Rabbits were given fluorescein or fluorescein glucuronide intravenously. Fluorescein and fluorescein glucuronide concentrations in plasma and vitreous samples were measured by high-performance liquid chromatography. Vitreous fluorophotometry was performed using the Fluorotron Master to compare scans after administration of fluorescein and fluorescein glucuronide, and for comparison of in vivo fluorescence with in vitro high-performance liquid chromatography analysis. Fluorescein glucuronide was shown to enter the vitreous as early as 1 hr after injection. Fluorescein glucuronide was the dominant molecule in both vitreous and plasma of all rabbits at 6 hr. Because fluorescein glucuronide has a lower fluorescence than fluorescein, the fluorophotometer overestimates the vitreous concentration of fluorescein after its administration. Since fluorescein is metabolized rapidly to fluorescein glucuronide in man, entry of fluorescein glucuronide into the eye should be considered in measurements of blood-ocular barrier permeability by vitreous fluorophotometry.


Partition coefficients for the trihalomethanes among blood, urine, water, milk and air.
Chloroform, bromodichloromethane, chlorodibromomethane, and bromoform comprise the trihalomethanes, a group of widespread and mildly lipophilic compounds that result from water chlorination and other sources. Many animal studies show the chronic toxicity and carcinogenicity of these compounds, and recent work has demonstrated the importance of both ingestion and inhalation exposure pathways. This study presents partition coefficients describing the equilibrium among biological compartments (air, water, blood, milk, urine) for the four THMs based on results of headspace gas chromatographic analyses performed under equilibrium conditions and at 37 degrees C. The calculated partition coefficients ranged from 2.92 to 4.14 for blood/water, 1.54-2.85 for milk/blood, and 3.41-4.93 for blood/urine, with the lowest being chloroform and the highest being bromoform. Both human and cow milk were tested, with similar results. The available samples of human milk may not fully account for differences in lipid content and possibly other factors that affect estimates of partition coefficients. Simultaneous measurements of milk and blood in exposed individuals are suggested to confirm laboratory results. Partition coefficients are predicted using the octanol-air partition coefficient, also measured in this study, and the octanol-water partition coefficient. Results are similar to literature estimates for liquid/air partitioning of chloroform and chlorodibromomethane, but they differ from predictions based on hydrophobicity and lipid content. High correlations between the derived partitioned coefficients and the molecular structure (number of Br atoms) and physical properties (molecular weight and boiling point) are found for these analogous chemicals. In humans, THMs are both stored and metabolized with relatively rapid clearance rates. The derived partition coefficients can help to interpret results of biological monitoring and predict the potential for the accumulation and transfer of chemicals, specifically by the application of physiologically-based pharmacokinetic models. THM exposures to potentially susceptible populations, e.g. nursing infants, can be predicted using either such models.


«Poppers maculopathy?» in Spain. A new ophthalmological disease.
The term «poppers» refers to products made of volatile alkyl nitrites used for recreational practices. 40 year old man reported blurred vision in both eyes and photophobia, and admitted regular use of «poppers». Best corrected visual acuity was 0.63/1 in both eyes. Bilateral yellowish vitelliform macular lesions were present in both eyes in the funduscopy, as well as a disruption of the IS/OS line in the optical coherence tomography. This is the first case of «poppers maculopathy» registered in Spain. Clinical findings and symptoms are similar to previous reported cases.


Erratum to: Rapid, modular, and cost-effective generation of donor DNA constructs for CRISPR-based gene knock-in.
[This corrects the article DOI: 10.1093/biomethods/bpaa006.].


Dissemination of Erroneous Research Findings and Subsequent Retraction in High-Circulation Newspapers: A Case Study of Alleged MDMA-Induced Dopaminergic Neurotoxicity in Primates.
Ensuring the public is informed of retractions has proven difficult for the scientific community. While it is possible that newspapers focus differential attention on publication of scientific articles and their subsequent retractions, this topic has received minimal attention from researchers. To learn more, we analyzed newspaper coverage of the high-profile 2002 article Severe dopaminergic neurotoxicity in primates after a common recreational dose regimen of MDMA ("ecstasy") and its retraction in a case study. We searched the 50 largest American newspapers with available online archives for stories about the article's publication and retraction. Of the 50 newspapers, 26 (52%) covered the article's publication and 20 (40%) its retraction. Six of the 50 newspapers (12%) published stories on the article's retraction without covering its initial publication. Of the 26 newspapers covering the article's publication, only 14 (54%) covered its retraction. Stories about the retraction were balanced, but shorter than those on the article's publication and often lacking in context and detail. While the decrease in coverage of the article's retraction was moderate among the entire sample, the much lower retraction coverage in newspapers that had already covered the article's publication is concerning and emphasizes the need for increased media coverage of retractions.


Highly toxic Cr (VI) adsorption by (chitosan-g-PMMA)/silica bionanocomposite prepared via emulsifier-free emulsion polymerisation.
This work focuses on developing some composites of desirable properties mainly for heavy metal ion adsorption from the water bodies leading to water remediation. Adsorption of Cr(VI) by a novel biopolymer-based hybrid nanocomposite material has been synthesized via emulsifier-free emulsion polymerisation technique and investigated its assess as proposed use. Chitosan is a biocompatible, biodegradable and non-toxic material, hence this biopolymer has been selected in this research work. The chemical modification of the biopolymer chitosan has been achieved via grafting of poly(methyl methacrylate) (PMMA) and crosslinker silica gel was added in order to improve the mechanical strength of the nanocomposite in nitrogen atmosphere taking ammonium persulphate as initiator. The resulting composite samples were characterized by using XRD, FTIR, SEM and TEM. Further, the biodegradability of the samples was studied at different time intervals from 15days to 6months and the so produced nanocomposite exhibited good biodegradability. Adsorption of Chromium (Cr) was investigated by varying the contact time between the adsorbate (Cr), the nanocomposite, pH of the solution and the doses of the composite. The optimum result for chromium removal was found at pH-4 and this result showed its use efficiently for the treatment of wastewater containing Cr (VI).


Culture of human vascular endothelial cells on a positively charged polystyrene surface, primaria: comparison with fibronectin-coated tissue culture grade polystyrene.
Two culture surfaces, fibronectin-coated tissue culture grade polystyrene and a surface-modified polystyrene called Primaria (Falcon), were compared. The morphological (contact inhibition and cobblestone aspect), biological (production of von Willebrand factor and prostacyclin) and physiological (growth activity, non-thombogenicity and regeneration after mechanical injury) properties of human endothelial cells were studied. Adhesion and growth of endothelial cells at low and clonal density were identical on both substrates and the biological properties were preserved. Regeneration of injured endothelium was less easy to study on Primaria polystyrene because the extracellular matrix was damaged during the lesion process. Nevertheless, Primaria polystyrene can easily be substituted for fibronectin coating in growth experiments, especially at very low seeding density.


Tissue response of several polymeric materials implanted in the rat middle ear.
Implantation of three different polymeric composite materials in the rat middle ear showed that the nylon prosthesis was encapsulated more rapidly than the two poly(methyl methacrylate) based implants. Several PMMA based implants were only partially covered at the 6 mnth stage by a tenuous capsule made up of collagen and a mixed inflammatory cell infiltrate. The nylon material was covered at the 3 mnth stage with a thin capsule and healthy fibroblasts.


Prosocial behavior and childhood trajectories of internalizing and externalizing problems: The role of neighborhood and school contexts.
This study investigated the role of the interaction between prosocial behavior and contextual (school and neighborhood) risk in children's trajectories of externalizing and internalizing problems at ages 3, 5, and 7. The sample was 9,850 Millennium Cohort Study families who lived in England when the cohort children were aged 3. Neighborhood context was captured by the proportion of subsidized (social rented) housing in the neighborhood and school context by school-level achievement. Even after adjustment for child- and family-level covariates, prosocial behavior was related both to lower levels of problem behavior at school entry and to its trajectory before and after. Neighborhood social housing was related to the trajectory of problem behavior, and school-level achievement to lower levels of problem behavior at school entry. The negative association between prosocial and problem behavior was stronger for children attending low-performing schools or living in disadvantaged neighborhoods. The adverse "effect" of low prosocial behavior, associated with low empathy and guilt and with constricted emotionality, on internalizing and externalizing problems appears to be exacerbated in high-risk contexts.


Helical oligomers of thiazole-based γ-amino acids: synthesis and structural studies.
9-Helix: 4-Amino(methyl)-1,3-thiazole-5-carboxylic acids (ATCs) were synthesized as new γ-amino acid building blocks. The structures of various ATC oligomers were analyzed in solution by CD and NMR spectroscopy and in the solid state by X-ray crystallography. The ATC sequences adopted a well-defined 9-helix structure in the solid state and in aprotic and protic organic solvents as well as in aqueous solution.


Establishment of procedures provoking sub-lethal injury of Listeria monocytogenes, Campylobacter jejuni and Escherichia coli O157 to serve method performance testing.
In this study procedures provoking sub-lethal injury for three different pathogens are described which may be used in determination of accuracy and robustness of methods, comparison studies and or validation of rapid detection methods. Three common food-borne pathogens were used, Listeria monocytogenes, Campylobacter jejuni and Escherichia coli O157. The pathogens were exposed to heat stress, cold stress, freeze stress, acid stress, oxidative stress and "food" stress. Sub-lethal injury was determined by plating in parallel on selective and non-selective media. The statistical significant differences in enumeration were established. The choice of stress to create sub-lethal injury to cells depended on the fact that the procedure must be easy to handle, repeatable and relevant for stress conditions in foods, but also on the micro-organism itself. Oxidative stress (1000 microM H(2)O(2)) was chosen to impose sub-lethal injury on L. monocytogenes and a specific "food" stress for E. coli O157. For C. jejuni a specific "food" stress as well as the oxidative stress (750 microM H(2)O(2)) were capable of creating a standardized procedure of provoking injury.


Changes in symptoms of anxiety, depression, and PTSD in an RCT-study of dentist-administered treatment of dental anxiety.
Educating dentists in treatment methods for dental anxiety would increase the patients' access to treatments that are important to their oral health. However, to avoid adverse effects on comorbid symptoms, involvement by a psychologist has been considered necessary. The objective of the present paper was to evaluate whether a dentist could implement systematized treatments for dental anxiety without an increase in comorbid symptoms of anxiety, depression or PTSD. A two-arm parallel randomised controlled trial was set in a general dental practice. Eighty-two patients with self-reported dental anxiety either completed treatment with dentist-administered cognitive behavioural therapy (D-CBT, n = 36), or received dental treatment while sedated with midazolam combined with the systemized communication technique "The Four Habits Model" (Four Habits/midazolam, n = 41). Dental anxiety and comorbid symptoms were measured pre-treatment (n = 96), post-treatment (n = 77) and one-year after treatment (n = 52). An Intention-To-Treat analysis indicated reduced dental anxiety scores by the Modified Dental Anxiety Scale (median MDAS: 5.0 (-1,16)). The median scores on the Hospital Index of Anxiety and Depression (HADS-A/D) and the PTSD checklist for DSM-IV (PCL) were reduced as follows: HADS-A: 1 (-11, 11)/HADS-D: 0 (-7, 10)/PCL: 1 (-17,37). No between-group differences were found. The study findings support that a general dental practitioner may treat dental anxiety with Four Habits/Midazolam or D-CBT without causing adverse effects on symptoms of anxiety, depression or PTSD. Establishing a best practice for treatment of patients with dental anxiety in general dental practice should be a shared ambition for clinicians, researchers, and educators. The trial was approved by REC (Norwegian regional committee for medical and health research ethics) with ID number 2017/97 in March 2017, and it is registered in clinicaltrials.gov 26/09/2017 with identifier: NCT03293342.


Laparoscopic pyeloplasty versus antegrade endopyelotomy: comparison in 100 patients and a new algorithm for the minimally invasive treatment of ureteropelvic junction obstruction.
The aim of this article is to assess the treatment efficacy of percutaneous endopyelotomy and laparoscopic pyeloplasty to establish a new algorithm in the minimally invasive treatment of ureteropelvic junction obstruction (UPJO). Hospital records, office charts, and radiographic studies of patients with UPJO treated either endoscopically (n = 50), laparoscopically (n = 50), or by endopyeloplasty (n = 5) were reviewed. All percutaneous endopyelotomies were performed with a cold hook-knife technique, and all laparoscopic pyeloplasties were performed transperitoneally using an Anderson-Hynes dismembered anastomosis. Successful outcomes were defined as relief of obstruction as quantified by diuretic renal scans and/or relief of obstructive symptoms. All patients were followed for an average of 16.0 months (range, 2 to 42 months). In the endoscopically treated group, the average age was 44.6 +/- 15.6 years, estimated blood loss (EBL) was 152.1 +/- 112.8 mL, and the hospital stay was 2.5 +/- 1.0 days. There was no significant change from preoperative to postoperative creatinine (1.2 +/- 0.7 mg/dL to 1.2 +/- 0.7 [106 +/- 62 micromol/L +/- 106 +/- 62 micromol/L]). Success rates included 92% (35 of 38) for primary percutaneous antegrade endopyelotomy and 58% (7 of 12) for secondary percutaneous antegrade endopyelotomy. All of the primary percutaneous antegrade endopyelotomy failures (n = 3) had either grade 3 or grade 4 hydronephrosis. In the laparoscopic pyeloplasty group the average age was 37.9 +/- 14.8 years, EBL was 108.3 +/- 109.4 mL, and the average hospital stay was 2.6 +/- 0.9 days. There was no significant change from preoperative to postoperative creatinine (1.1 +/- 0.4 mg/dL to 1.0 +/- 0.4 mg/dL [97 +/- 35 micromol/L to 97 +/- 35 micromol/L]). Success rates included 100% (29 of 29) for primary repair and 95.2% (20 of 21) for secondary repair. There was no statistical difference in preoperative patient parameters or objective outcomes when comparing primary endopyelotomy and primary laparoscopic pyeloplasty. In skilled hands, highly successful outcomes can be expected when either antegrade endopyelotomy or laparoscopic pyeloplasty is used to treat a primary UPJO. In the instance of a UPJO associated with a high degree of hydronephrosis, patients may be better served with a laparoscopic pyeloplasty. To maximize an efficacious outcome, minimally invasive UPJO treatment decisions should be based on patient and surgeon preference, as directed by the presented algorithm.


EGFR-dependent pancreatic carcinoma cell metastasis through Rap1 activation.
Tyrosine kinase receptors have an essential role in various aspects of tumor progression. In particular, epidermal growth factor receptor (EGFR) and its ligands have been implicated in the growth and dissemination of a wide array of human carcinomas. Here, we describe an EGFR-mediated signaling pathway that regulates human pancreatic carcinoma cell invasion and metastasis, yet does not influence the growth of primary tumors. In fact, ligation/activation of EGFR induces Src-dependent phosphorylation of two critical tyrosine residues of p130CAS, leading to the assembly of a Crk-associated substrate (CAS)/Nck1 complex that promotes Ras-associated protein-1 (Rap1) signaling. Importantly, GTP loading of Rap1 is specifically required for pancreatic carcinoma cell migration on vitronectin but not on collagen. Furthermore, Rap1 activation is required for EGFR-mediated metastasis in vivo without impacting primary tumor growth. These findings identify a molecular pathway that promotes the invasive/metastatic properties of human pancreatic carcinomas driven by EGFR.


Evaluating Clinical Practice Guidelines Based on Their Association with Return to Work in Administrative Claims Data.
To examine the association between non-adherence to clinical practice guidelines (CPGs) and time to return to work (RTW) for patients with workplace injuries. Secondary analysis of medical billing and disability data for 148,199 for shoulder and back injuries from a workers' compensation insurer. Cox proportional hazard regression is used to estimate the association between time to RTW and receipt of guideline-discordant care. We test the robustness of our findings to an omitted confounding variable. Collected by the insurer from the time an injury was reported, through recovery or last follow-up. Receiving guideline-discordant care was associated with slower RTW for only some guidelines. Early receipt of care, and getting less than the recommended amount of care, were correlated with faster RTW. Excessive physical therapy, bracing, and injections were associated with slower RTW. There is not a consistent relationship between performance on CPGs and RTW. The association between performance on CPG and RTW is difficult to measure in observational data, because analysts cannot control for omitted variables that affect a patient's treatment and outcomes. CPGs supported by observational studies or randomized trials may have a more certain relationship to health outcomes.


Synthesis and 188Re radiolabelling of dendrimer polyamide amine (PAMAM) folic acid conjugate.
Folic acid receptors (FR) are usually over expressed in many cancer cells and are considered as potential targeted therapy agent. Generation of five polyamido amine (PAMAM) dendrimer folic acid conjugate was synthesised and radiolabelled with (188)Re, furthermore the in vitro/in vivo stability was evaluated accordingly. The labelling yield of the conjugate G5-FA-DTPA-(188)Re was 67.1% and its radiochemical purity exceeded 95%. The conjugate also showed high in vitro stability and potential value for further structure modifications and evaluations.


"Bow-tie" mitral valve repair: an adjuvant technique for ischemic mitral regurgitation.
Current techniques of mitral valve repair rely on decreasing valve area to increase leaflet apposition, but fail to address subvalvular dysfunction. A novel repair has been introduced with partial left ventriculectomy, which apposes the anterior leaflet to a corresponding point on the posterior leaflet creating a double-orifice valve, with reported adequate control of mitral regurgitation. We started to use the "bow-tie" repair as an adjunct to posterior ring annuloplasty in cases in which mitral regurgitation was not adequately controlled by decreasing mitral valve area (n = 6), or when placement of an annuloplasty ring was impractical (n = 4). Mean follow-up was 336 days (range, 82 to 551 days) with no postoperative deaths. Mitral regurgitation decreased from 3.6+/-0.5 to 0.8+/-0.4 (p < 0.0001), with a concomitant increase in ejection fraction from 33%+/-13% to 45%+/-11% (p = 0.0156) before hospital discharge. Mitral valve area, measured by pressure half-time, decreased from a mean of 2.5+/-0.3 to 2.1+/-0.3 cm2, with a mean transvalvular gradient of 4.5+/-2.0 mm Hg. In patients whose mitral valve was repaired using the bow-tie alone, mitral regurgitation was reduced from 4+, to a trace to 1+. Postoperatively, mitral valve area increased from 1.9 to 2.5 cm2 during exercise, further supporting the concept that this technique preserves mitral valve annular function. These observations suggest that the bow-tie repair may offer advantages over conventional techniques of mitral valve repair and should be considered as an adjunct, especially in patients with impaired left ventricular function.


Dofetilide use is not associated with increased mortality in patients with left ventricular hypertrophy and atrial fibrillation.
Left ventricular hypertrophy (LVH) is common in patients with atrial fibrillation (AF), however, many antiarrhythmic drugs (AADs) are contraindicated. US guidelines recommend avoiding pure class III antiarrhythmics such as dofetilide in patients with significant LVH due to concern for an increased risk of death, however, clinical data is lacking. We sought to determine if dofetilide use was associated with increased mortality in patients with LVH. Patients ≥18 years of age with AF and LVH ≥ 1.4 cm were included. A group of patients treated with dofetilide and a control group of patients without a history of AAD use were propensity matched. The primary outcome was all-cause mortality at 3 years and secondary outcomes were total number of all-cause hospitalizations and hospitalizations related to AF. There were 359 patients in each of the groups. Baseline variables were well-matched. The primary outcome of all-cause mortality occurred in 7% of patients in the dofetilide group and 12% of patients in the control group (hazard ratio: 0.90, 95% confidence interval: 0.53-1.53). Total all-cause hospitalizations were higher in the control group but hospitalizations for AF were no different. In a propensity-matched cohort of 718 patients with AF and LVH, dofetilide was not associated with increased mortality at 3 years. Our study adds to prior data demonstrating the safety of dofetilide in this population despite guideline recommendations against its use. Given the limited options for AF management in LVH patients, dofetilide may be reasonable for symptomatic AF management.


Characterization of Two Complete Mitochondrial Genomes of Ledrinae (Hemiptera: Cicadellidae) and Phylogenetic Analysis.
Mitochondrial genomes are widely used for investigations into phylogeny, phylogeography, and population genetics. More than 70 mitogenomes have been sequenced for the diverse hemipteran superfamily Membracoidea, but only one partial and two complete mtgenomes mitochondrial genomes have been sequenced for the included subfamily Ledrinae. Here, the complete mitochondrial genomes (mitogenomes) of two additional Ledrinae species are newly sequenced and comparatively analyzed. Results show both mitogenomes are circular, double-stranded molecules, with lengths of 14,927 bp (Tituria sagittata) and 14,918 bp (Petalocephala chlorophana). The gene order of these two newly sequenced Ledrinae is highly conserved and typical of members of Membracoidea. Similar tandem repeats in the control region were discovered in Ledrinae. Among 13 protein-coding genes (PCGs) of reported Ledrinae mitogenomes, analyses of the sliding window, nucleotide diversity, and nonsynonymous substitution (Ka)/synonymous substitution (Ks) indicate atp8 is a comparatively fast-evolving gene, while cox1 is the slowest. Phylogenetic relationships were also reconstructed for the superfamily Membracoidea based on expanded sampling and gene data from GenBank. This study shows that all subfamilies (sensu lato) are recovered as monophyletic. In agreement with previous studies, these results indicate that leafhoppers (Cicadellidae) are paraphyletic with respect to the two recognized families of treehoppers (Aetalionidae and Membracidae). Relationships within Ledrinae were recovered as (Ledra + (Petalocephala + Tituria)).


One-step laparoscopy-guided abomasopexy versus omentopexy via right flank laparotomy to treat left displaced abomasum in dairy cows, in relation to return of milk yield.
This study compared two surgical techniques for treating left displaced abomasum (LDA) in dairy cows. The two techniques were compared in terms of milk production at different time intervals: before surgery; on the day of the surgery; and at 8, 15 and 30 days after surgery. The surgical techniques used in this study were laparoscopy-guided abomasopexy and right flank laparotomy omentopexy. A total of 126 lactating Holstein-Friesian cows with LDA were included, 63 of which were treated with laparoscopy, and 63 with right flank laparotomy. Cows with retained foetal membranes, metritis or natural delivery (dystocia) were included and registered on field sheets for subsequent statistical analysis. Cows with clinical mastitis were excluded. A blood sample (5 mL) was obtained from the medial coccygeal vein and analyzed for total proteins, total bilirubin, total calcium, glucose, b-hydroxybutyrate, sodium, potassium, and chloride. No differences were found between the two groups of operated cows with respect to the number of lactation days, body condition score (BCS), rectal temperature, heart rate, and respiratory rate before surgery. No differences were observed between groups regarding the biochemical parameters (P > 0.05) analyzed, except for chloride, which presented lower average values in the omentopexy group (P <0.05). Return of milk yield within the study period did not differ significantly between the laparoscopy and laparotomy groups (P > 0.05), although a significant change in post-surgery time was observed. .


Sultam based Carbonic Anhydrase VII inhibitors for the management of neuropathic pain.
We report a series of compounds 1-17 derived from the antiepileptic drug Sulthiame (SLT) from which both the benzenesulfonamide and the sultam moiety were retained. All compounds were tested in vitro for their inhibition activity against the human (h) Carbonic Anhydrase (CA; EC 22.214.171.124) I, II, VII, IX and XII isoforms. Among the series, derivatives 1 and 11 showed great enhancement of both inhibition potency and selectivity towards the hCA VII isoform, when compared to the reference SLT drug. The binding mode of 11 within the hCA VII active site was deciphered by means of X-ray crystallography and revealed the sultam moiety being exposed to the rim of the active site. In vivo experiments on a model of neuropathic pain induced by oxaliplatin clearly showed 11 being an effective pain relieving agent and therefore worth of further exploitation towards the validation of the hCA VII as new target for the management of neuropathies.


Incidence and mortality of non-AIDS-defining cancers among people living with HIV: A systematic review and meta-analysis.
Non-AIDS-defining cancers (NADCs) are now becoming a rising cause of morbidity among people living with HIV (PLHIV) in the highly active antiretroviral therapy (HAART) era. We conducted a systematic review and meta-analysis to estimate the summary risk of incidence and mortality of a wide range of NADCs among PLHIV compared with the general population. This systematic review and meta-analysis was registered in the PROSPERO (registration number CRD42020222020). We searched PubMed, EMBASE, Cochrane library, and Web of Science for relevant studies published before Jan 24, 2022. Cohort or registry linkage studies comparing the incidence or mortality of individual NADCs in PLHIV with that in the general population were included. Studies simply reporting outcomes of cancer precursor lesions or combined NADCs were excluded. We calculated pooled standardised incidence (SIRs) and standardised mortality ratios (SMRs) and their 95% confidence intervals (CIs) using random-effects models, and used robust variance estimation to account for non-independence in study-level effect sizes. We identified 92 publications arising from 46 independent studies including 7 articles out of 7 studies from developing countries. Among the 40 types of NADCs investigated, all of the 20 infection-related NADCs, cancers related with human papillomavirus infection in particular, and half of the 20 non-infection-related NADCs occurred in excess in PLHIV compared with the general population. This risk pattern was consistent in most WHO regions and in both high-income and low-and middle-income countries. The increased SIRs for various NADCs were more evident among PLHIV with advanced immunodeficiency, and was explored by HIV transmission route, and use of HAART. PLHIV had increased mortality for anal cancer (SMR 124·07, 95% CI 27·31-563·72), Hodgkin lymphoma (41·03, 2·91-577·88), liver cancer (8·36, 3·86-18·11), lung cancer (3·95, 1·52-10·26), and skin melanoma (3·95, 1·28-12·2). PLHIV had increased incidence and mortality for a wide spectrum of NADCs. Primary prevention and effective treatment for NADCs in this population is urgently needed. Natural Science Foundation of China Excellent Young Scientists Fund, Natural Science Foundation of China International/Regional Research Collaboration Project, National Science and Technology Major Project of China, Sanming Project of Medicine in Shenzhen, High Level Project of Medicine in Longhua, Shenzhen, Shenzhen Science and Technology Innovation Commission Basic Research Program, Special Support Plan for High-Level Talents of Guangdong Province, the Guangzhou Basic Research Program on People's Livelihood Science and Technology, the National Natural Science Foundation of China.


Influence of interface surface conditions on indentation failure of simulated bonded ceramic onlays.
This study aims to evaluate the influence of surface roughness and acid etching on interfacial failure load and fracture initiation site for simulated resin bonded ceramic restorations. Layered disks were fabricated using soda lime glass to simulate porcelain and fiberglass to represent dentin. These materials were selected due to their approximate elastic modulus to porcelain or dentin. In addition, soda lime glass allowed for visualization of crack initiation. Glass microscope slides (1.2 mm thick) were sectioned into 1-mm2 specimens. The frosted portions of the slides were used as the rough or sandblasted group and the clear areas were used as the smooth or polished group. All surfaces were either cleaned or etched. Prepared surfaces were divided into eight groups and bonded to the substrates using Optibond Solo Plus (SDS Kerr, Orange, CA) and Nexus resin cement (SDS Kerr). Support substrates were made from 5-mm slices of fiberglass rods (1/2 in. diameter). Vertical loads were applied to the layered disks with a 20-mm spherical indenter at a cross-head speed of 0.05 mm/min. Observations were made using 10x magnification with a video monitor. Load magnitudes were recorded at the time of crack initiation. Weibull parametric survival analysis and the effect likelihood ratio test were performed on the failure initiation load data to determine significant differences at the 0.05 level. Mean failure initiation loads ranged from 273.6 to 341.9N for the rough specimens and from 1056.5 to 2980.2N for the smooth samples. According to the Weibull parametric survival analysis and the effect likelihood ratio test, surface roughness and surface etch significantly influenced failure initiation loads. Smoother surfaces tolerated much greater contact loads before failure initiation. The clinical performance of all-ceramic restorations may be improved with smoother internal surfaces. Etching significantly increases survival for restorations with smooth internal surfaces.


Quantification of six volatile oil constituents of Oleum Cinnamomi in rat plasma and multiple tissues using GC-MS and its application to pharmacokinetic and tissue distribution studies.
Oleum Cinnamomi is the essential oil obtained from the herb Fructus Cinnamomi which is used by the Hmong people in traditional medicine for the treatment of various diseases. At present, there are a variety of marketed preparations with it as the main medicine on the market. Information regarding the in vivo process of it is lacking, which has become a bottleneck restricting its development and utilization. In view of this, a GC-MS SIM analysis method was established for the simultaneous determination of six main volatile components [eucalyptol, p-cymene, 4-carvomenthenol, 4-isopropyl-2-cyclohexenone, α-terpineol, and 2-(4-Methylphenyl)-propan-2-ol] in plasma and ten tissues of rats to study their pharmacokinetic and distribution characteristics in vivo. The pharmacokinetic results showed that the t1/2 of each index was 0.41-1.66 h, Tmax was 0.16-0.68 h, Cmax was 13.66-2015.02 ng/mL, AUC0-t was 12.84-4299.00 h·ng/mL, CLZ/F was 1750.93-107013.11 mL/h/kg. This meant that the six components could be absorbed quickly, had a short residence time, and be eliminated quickly in the body. Among them, eucalyptol has the highest degree of absorption and a larger amount of entering the body. Moreover, the Cmax and AUC0-t of the six components increased correspondingly with the increase of the dose, indicating that the concentration of Oleum Cinnamomi in the rat plasma was dose-dependent. At different time points, the six components were widely distributed with uneven characteristics in the body. The six components mainly tend to be distributed in stomach, small intestine, and liver, followed by kidney, spleen, heart, and brain, and to a lesser extent in lung, skin, and muscle. And the six components were eliminated quickly in each tissue. The pharmacokinetic process and tissue distribution characteristics of Oleum Cinnamomi were expounded in this study, which can provide scientific theory for the in-depth development and guidance of clinical drug use of Oleum Cinnamomi, and at the same time provide a medicinal material basis for the in-depth development and utilization of Oleum Cinnamomi.


Surgical management of broad-based sessile vocal cord polyps: Transnasal vocal fold polypectomy versus microlaryngoscopic surgery: Our experience in 159 cases.
In this study, we retrospectively reviewed and compared the treatment outcomes and complications of office transnasal vocal fold polypectomy (TVFP) with those of microplarygoscopic surgery (MLS) for different clinical and histopathological features of broad-based sessile vocal fold polyps. We retrospectively reviewed the records of 159 consecutive patients with broad-based sessile vocal fold polyps treated by TVFP or MLS. The differences in efficacy and complication between these two surgical techniques were compared according to the different types of vocal fold polyps. Satisfactory outcomes of both TVFP and MLS treatments were reported in patients with oedematous, gelatinous and vascular types of vocal fold polyps (p > .05). The efficacy of TVFP was slightly worse than MLS in fibrous polyps group (p < .05). The TVFP-treated patients did not exhibit obvious complications, whereas several MLS-treated patients had suffered different complications. The therapeutic effects of both TVFP and MLS on the treatment of broad-based sessile vocal cord polyps are related to their clinical characteristics and histological types. Satisfactory outcomes are achieved in oedematous, gelatinous, and vascular types of polyps after either surgical procedure. TVFP has fewer surgical complications than MLS which can be a preferred option for the treatment of broad-based sessile vocal cord polyps at outpatient setting. TVFP also can be an alternative surgery option for patients who could not tolerate general anaesthesia or laryngeal suspension. In contrast, MLS has proven to be a particularly advantageous treatment in patients who have fibrous type of polyps.


Alpha-hemoglobin-stabilizing protein (AHSP) in hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome, intrauterine growth restriction (IUGR) and fetal death.
Alpha hemoglobin-stabilizing protein (AHSP) inhibits the production of reactive oxygen species in various cells, including erythrocytes. Reduced AHSP can mean reduced protection from stressors. Our objective was to investigate whether AHSP is involved in the response to stress in pregnancy. Placentas were collected from normal term pregnancies (n = 10) and pregnancies complicated by HELLP (n = 10), intrauterine growth restriction (IUGR; n = 10) or fetal death (IUFD; n = 6). AHSP messenger RNA (mRNA) and protein were determined using real time quantitative polymerase chain reaction (PCR) and Western blot, respectively. All statistical analyses were performed by using the GraphPad Prism Software. Differences were considered significant at p < 0.05. Placental AHSP mRNA level in HELLP (4.16E10(-4) +/- 1.77) and IUFD (4.19E10(-4) +/- 3.37) were significantly decreased compared with controls (28.47E10(-4) +/- 14.86; p < 0.01), whereas levels in the IUGR group (7.55E10(-4) +/- 6.4) showed a trend toward being lower but the difference did not reach statistical significance. Western blot analysis results indicate a no significant increase of ASHP protein in the HELLP syndrome group and a significant decrease in the IUFD group compared with controls. There was no significant difference between the IUGR and control groups. ASHP mRNA expression in the placenta is decreased in complicated pregnancies, and it may be involved in the pathogenic mechanisms leading to the adverse pregnancy outcome.


Neighborhood disadvantage is associated with KRAS-mutated non-small cell lung cancer risk.
It remains unclear why individuals living in disadvantaged neighborhoods have shorter non-small cell lung cancer (NSCLC) survival. It is possible that living in these deprived areas is linked with increased risk of developing aggressive NSCLC biology. Here, we explored the association of somatic KRAS mutations, which are associated with shorter survival in NSCLC patients, and 11 definitions of neighborhood disadvantage spanning socioeconomic and structural environmental elements. We analyzed data from 429 NSCLC patients treated at a Comprehensive Cancer Center from 2015 to 2018. Data were abstracted from medical records and each patient's home address was used to assign publicly available indices of neighborhood disadvantage. Prevalence Ratios (PRs) for the presence of somatic KRAS mutations were estimated using modified Poisson regression models adjusted for age, sex, smoking status, race/ethnicity, educational attainment, cancer stage, and histology. In the NSCLC cohort, 29% had KRAS mutation-positive tumors. We found that five deprivation indices of socioeconomic disadvantage were associated with KRAS mutation. A one decile increase in several of these socioeconomic disadvantage indices was associated with a 1.06 to 1.14 increased risk of KRAS mutation. Measures of built structural environment were not associated with KRAS mutation status. Socioeconomic disadvantage at the neighborhood level is associated with higher risk of KRAS mutation while disadvantage related to built environmental structural measures was inversely associated. Our results indicate not only that neighborhood disadvantage may contribute to aggressive NSCLC biology, but the pathways linking biology to disadvantage are likely operating through socioeconomic-related stress.


[Effect of several inhibitors of atmospheric metal corrosion (amines of the polymethylene series) on embryogenesis].
The influence of some polymethylene amines (inhibitors protecting metals from atmospheric corrosion) on the generative function in general and on the embryogenesis in particular was studied. Such inhibitors as MCDA-II (dicyclohexylamine salt dissolving in oil), HDA (dicyclohexylamine nitrate) and M-I (cyclohexylamine salt dissolving in oil) were investigated by intraorganic injection during the whole course of gestation (21 days), 2 and 4 months. The compounds in question were stated to possess a pronounced gonado- and embryotoxic effect depending on the dose and chemical composition of the substance. The least active was M-I inhibitor. Doses not affecting rat gonades were: for HDA--0.825 mg/kg, MCDA-II--4.7 mg/kg, M-I--34.9 mg/kg; their embryonic effects were 0.54, 2.35 and 349 mg/kg respectively.


Preventing coronary artery disease in the West of Scotland: implications for primary prevention.
The effectiveness of plasma cholesterol reduction therapy is no longer in question. Recent studies of cholesterol-lowering drug therapy demonstrate significant reductions in risks of mortality and coronary events in patients with existing coronary artery disease. The West of Scotland Coronary Prevention Study (WOSCOPS) demonstrated the therapy's effectiveness as primary prevention in patients without demonstrated coronary artery disease. Now that the efficacy of lipid reduction has been demonstrated conclusively, we face the difficult question of deciding what the treatment goals should be, whom to treat, and how to make those decisions cost effectively. These questions have complex social and ethical components and will lead to considerable discussion about how lipid-decreasing drugs will be used.


Managing meiotic recombination in plant breeding.
Crossover recombination is a crucial process in plant breeding because it allows plant breeders to create novel allele combnations on chromosomes that can be used for breeding superior F1 hybrids. Gaining control over this process, in terms of increasing crossover incidence, altering crossover positions on chromosomes or silencing crossover formation, is essential for plant breeders to effectively engineer the allelic composition of chromosomes. We review the various means of crossover control that have been described or proposed. By doing so, we sketch a field of science that uses both knowledge from classic literature and the newest discoveries to manage the occurrence of crossovers for a variety of breeding purposes.


Unicentric Castleman's disease in the posterior cervical space mimicking a schwannoma.
Castleman's disease (CD) is a benign and rare lymphoid tissue disease of undetermined origin. It affects the neck infrequently; therefore its preoperative diagnosis is difficult and can be confused with other hypervascular lesions. We present a case of unicentric hyaline-vascular CD in the posterior cervical space (PCS) evaluated by MRI and initially presumed to be a cervical schwannoma. As shown with our case, unicentric CD should be included in the differential diagnosis for masses in the PCS, especially when a hypervascular lesion like a schwannoma is suspected. The finding of central low intensity areas in a fissured and radial pattern in T2 sequences can help to consider CD when dealing with PCS masses as shown by previous cases and our reported experience.


Twenty-five years with the biopsychosocial model of low back pain-is it time to celebrate? A report from the twelfth international forum for primary care research on low back pain.
An integrated review of current knowledge about the biopsychosocial model of back pain for understanding etiology, prognosis, and interventions, as presented at the plenary sessions of the XII International Forum on LBP Research in Primary Care (Denmark; October 17-19, 2012). To evaluate the utility of the model in reference to rising rates of back pain-related disability, by identifying (a) the most promising avenues for future research in biological, psychological, and social approaches, (b) promising combinations of all 3 approaches, and (c) obstacles to effective implementation of biopsychosocial-based research and clinical practice. The biopsychosocial model of back pain has become a dominant model in the conceptualization of the etiology and prognosis of back pain, and has led to the development and testing of many interventions. Despite this back pain remains a leading source of disability worldwide. The review is a synthesis based on the plenary sessions and discussions at the XII International Forum on LBP Research in Primary Care. The presentations included evidence-based reviews of the current state of knowledge in each of the 3 areas (biological, psychological, and social), identification of obstacles to effective implementation and missed opportunities, and identification of the most promising paths for future research. Although there is good evidence for the role of biological, psychological, and social factors in the etiology and prognosis of back pain, synthesis of the 3 in research and clinical practice has been suboptimal. The utility of the biopsychosocial framework cannot be fully assessed until we truly adopt and apply it in research and clinical practice. N/A.


Response of the lymph node to tumour antigen and Bacillus Calmette-Guerin in cattle bearing tumours of the ethmoturbinate region.
The immunological response of the Ln subiliacus (externus) in cattle bearing ethmoid carcinoma was studied. The lymph node was stimulated in vivo by I/D administration of tumour antigen and Bacillus Calmette-Guerin and the changes in the lymph node were studied at 3-day intervals up to 15 days. The histological changes in the lymph node were assessed and the functional activity of the activated macrophages in the lymph node impression smears was evaluated using Nitroblue tetrazolium salt reduction test. Similar studies were also undertaken in age-matched healthy nontumour bearing cattle. On stimulation with BCG and tumour antigen there was stimulation of the T cell dependent area. However, the response to the tumour antigen was quicker but shorter in duration compared with that to BCG. The response in healthy animals was proportionately much less. The studies indicated that tumour-bearing animals which were mostly in stage II were immunocompetent.


Effect of Bioritm-E phytococktail and experimental medicinal drug from spurdog liver Skvaakan on microcirculation, platelet aggregation, and thromboresistance of vascular wall in rats.
The study compared the effects of phytococktail Bioritm-E (a multicomponent phytoadaptogen) and experimental preparation Skvaakan from the liver of Black Sea spurdog on systemic homeostasis, microcirculation, and blood lipid profile in 15 days of their daily administration. Skvaakan enhanced the platelet activity producing no effect on vascular thromboresistance. Bioritm-E phytococktail inhibited platelet activity and enhanced vascular thromboresistance. Both agents modified blood lipid profile by decreasing concentration of triglycerides and HDL; in addition, they strengthened the vascular wall and increased vascular resistance. These findings attest to similarity of some biomedical features of phytoadaptogen Bioritm-E and hydrobiont Skvaakan, although they produced different biological effects on platelet activity and vascular thromboresistance.


Gout After Total Knee Arthroplasty.
Crystalline arthropathies are well-known pathologies in a native knee; however, the literature is scarce with regards to crystalline arthropathies in a total knee arthroplasty (TKA). The presentation of crystalline arthropathy in a TKA can be similar to a periprosthetic joint infection (PJI), making it difficult to distinguish between the 2 diagnoses. We present 1 case highlighting the similarity between crystalline arthropathy and PJI. A 71-year-old man with a history of bilateral TKAs presented with bilateral painful knee effusions and was initially presumed to have PJIs; however, he was later diagnosed with gout and successfully treated medically. A complete review of the literature demonstrates that crystalline arthropathies after TKA are infrequently reported and can be difficult to decipher from PJIs, and there is a lack of standardized treatment.


Economic assessments in randomized controlled trials.
When comparing costs and benefits of different medical strategies, cost-effectiveness analysis, cost-utility analysis and cost-benefit analysis may be used. Both direct and indirect costs and benefits must be considered. Integrating survival with a measure of quality of life such as a health status index permits calculation of quality of life adjusted years of survival (QALYS). In any trial where it is expected that a more expensive treatment is the most effective, a full economic assessment should be made. Examples are provided from the use of verapamil and propranolol in hypertension, naftidrofuryl in stroke and auranofin in the treatment of rheumatoid arthritis.


The effects of probe length on Fitts' law.
Experiments were aimed at determining the effect of a human using an extended probe when making movements that required accuracy at the completion of the movement. Ten subjects performed 64 conditions of varying amplitude of movement, final accuracy and probe length. Movement time increased with probe lengths from 100 to 400mm for all conditions of amplitude and required accuracy. The effect of probe length was included in a mathematical description of the data through a multiplicative term on Fitts' index of difficulty (ID), possibly arising from tremor of the hand probe system in controlling approach to the target. Probe length had the greatest effect at high ID, where a probe of 400 mm length increased movement time by about 25% over that for a 100mm probe. The model developed has application for accurate movements with long tools such as screwdrivers or crowbars, head-mounted devices for the disabled, or other tasks where the work interface is at the end of an extended probe.


Variations in Application Instructions for Forensic Psychiatry Fellowships.
In this study, the authors examined the consistency and the transparency of application instructions for forensic psychiatry fellowships in the USA. The authors collected the names of US forensic psychiatry fellowships listed in the Directory of Forensic Psychiatry Fellowships maintained by the American Academy of Psychiatry and the Law. Using data from active fellowship websites, the authors extracted for each program: (1) timelines for applications and interviews, (2) whether an application form was supplied, and (3) the presence of specific application requirements (e.g., curriculum vitae, personal statement, letters of recommendation, residency training director evaluations, writing samples). Among 45 fellowship websites, 31 (68.9%) did not provide specific dates or months when their application cycle opened, nor did they indicate whether they accepted applications on a rolling basis. Fourteen (31.1%) did not have an application form, and 8 (17.8%) did not list application requirements. Among 37 programs that listed specific requirements on their websites, 36 (97.3%) required a curriculum vitae or letters of recommendation, 35 (94.6%) required a personal statement and/or letter of interest, and 27 (73.0%) required writing samples and/or evaluation materials from residency program directors. This study found considerable variations among online application instructions for US forensic psychiatry fellowships. Although many factors shape recruitment into forensic psychiatry fellowships, improving the consistency and the transparency of application instructions might decrease stress related to the application cycle and streamline recruitment into the field.


Histopathologic differences due to bacterial species in acute otitis media.
To compare selected features of histopathology in acute otitis media caused by various bacteria and examine potential differences due to bacterial species, as well as possible correlation to experimental and human clinical findings. Rat models of acute otitis media caused by Streptococcus pneumoniae (MC), non-typeable or type b Haemophilus influenzae (NTHI/HIB) or Moraxella catarrhalis (MC) were studied longitudinally up to 6 months after bacterial challenge. Findings related to dynamics of goblet cell density, modeling and remodeling of bone tissue structures and polyp, as well as fibrous adhesion formation and persistence are presented. Middle ear goblet cell density progressed to peak 2 weeks after bacterial inoculation, thereafter gradually normalizing. However, density and accordingly middle ear secretory capacity was still significantly increased after 6 months in all bacteria, except MC. The HI species induced the highest increase. Initial osteoresorption was followed by massive osteoneogenesis, progressing to a peak after 2-3 months, followed by some degree of normalization, concurrently classic remodeling. Primarily SP, but also the HI species induced more new bone formation than MC. Mucosal polyp and fibrous adhesion formation occurred regardless of bacterial species. Most polyps appeared in the early phases and the HI species induced formation of more polyps and adhesions than the other bacteria. Acute middle ear infection with the Haemophilus species induce the highest increase of mucosal secretory capacity, lasting for at least 6 months after the acute incident. Thus, a subsequent development of secretory otitis media seems more likely following infection with these bacteria. Equivalently, mucosal scarring observed as polyp and fibrous adhesion formation was more severe following Haemophilus infection. S. pneumoniae induced the most marked changes of bone tissue structures, seen as initial osteoresorption and subsequent osteoneogenesis. Overall, infection with M. catarrhalis induced the mildest changes.