[Glucose-6 phosphatase catalytic subunit inhibits the proliferation of liver cancer cells by inducing cell cycle arrest].
Objective: To investigate the effects of glucose-6-phosphatase catalytic subunit (G6PC) recombinant adenovirus on proliferation and cell cycle regulation of liver cancer cells. Methods: Recombinant adenovirus AdG6PC was constructed. Huh7 cells and SK-Hep1 cells were set as Mock, AdGFP and AdG6PC group. Cell proliferation and clone formation assay were used to observe the proliferation of liver cancer cells. Transwell and scratch assay were used to observe the invasion and migration of liver cancer cells. Cell cycle flow cytometry assay was used to analyze the effect of G6PC overexpression on the proliferation cycle of liver cancer cells. Western blot was used to detect the effect of G6PC overexpression on the cell-cycle protein expression in liver cancer cells. Results: The recombinant adenovirus AdG6PC was successfully constructed. Huh7 and SK-Hep1 cells proliferation assay showed that the number of proliferating cells in the AdG6PC group was significantly lower than the other two groups (P < 0.05). Clone formation assay showed that the number of clones was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression could significantly inhibit the proliferation of liver cancer cells. Transwell assay showed that the number of cell migration was significantly lower in AdG6PC than the other two groups (P < 0.05). Scratch repair rate was significantly lower in AdG6PC than the other two groups (P < 0.05), suggesting that G6PC overexpression can significantly inhibit the invasion and migration of liver cancer cells. Cell cycle flow cytometry showed that G6PC overexpression had significantly inhibited the Huh7 cells G(1)/S phase transition. Western blot result showed that G6PC overexpression had down-regulated the proliferation in cell-cycle related proteins expression. Conclusion: G6PC inhibits the proliferation, cell-cycle related expression, and migration of liver cancer cells by inhibiting the G(1)/S phase transition.


Online patient resources for deceased donor and live donor kidney recipients: a comparative analysis of readability.
The Internet has extensive resources for kidney transplantation recipients. Half of the population reads below a seventh-grade level. Previous studies showed that living donor recipients have higher health literacy rates compared with deceased donor recipients. There has been no study comparing the readability of online living donor recipient materials versus deceased donor recipient materials. Analysis was performed using eight readability scales on the top 10 websites for live donor and deceased donor kidney transplantation. Analysis was performed through the Readability Studio Software. USA reading grade level was determined for each site. Overall, the mean reading level for the living donor materials was 12.54 (range 9.2-17) and for the deceased donor materials, 12.87 (range 8.7-17, P = 0.73), corresponding to a university level. None of the sites met the seventh-grade level recommended by the National Institute of Health. The readability of online materials remains too high for the corresponding health literacy rates among patients requiring kidney transplantation. Specifically, the lower health literacy rates among deceased donor recipients does not mirror the readability of online materials provided at a university level. This may affect decision-making, contributing to a smaller proportion of patients of a lower socioeconomic status and those with poor English language skills pursuing live donor organs.


A likelihood ratio test for a patterned covariance matrix in a multivariate growth-curve model.
In a multivariate growth-curve model, the estimator of the parameter matrix is a function of the matrix of the sums of squares and of the cross-products due to error. However, if the assumption of a patterned covariance matrix is valid, then the parameter estimator does not depend on the error matrix. A likelihood ratio test of this patterned covariance matrix is constructed and its distribution is discussed. A numerical example is provided in which the design consists of two treatment groups, with three repeated measures being taken of the three response variables.


Risk factors for acute kidney injury in critically ill patients with torso injury: A retrospective observational single-center study.
Acute kidney injury (AKI) is common in trauma patients and associated with poor outcomes. Identifying AKI risk factors in trauma patients is important for risk stratification and provision of optimal intensive care unit (ICU) treatment. This study identified AKI risk factors in patients admitted to critical care after sustaining torso injuries.We performed a retrospective chart review involving 380 patients who sustained torso injuries from January 2016 to December 2019. Patients were included if they were aged >15 years, admitted to an ICU, survived for >48 hours, and had thoracic and/or abdominal injuries and no end-stage renal disease. AKI was defined according to the Kidney Disease Improving Global Outcomes definition and staging system. Clinical and laboratory variables were compared between the AKI and non-AKI groups (n = 72 and 308, respectively). AKI risk factors were assessed using multivariate logistic regression analysis.AKI occurred in 72 (18.9%) patients and was associated with higher mortality than non-AKI patients (26% vs 4%, P < .001). Multivariate logistic regression analysis identified bowel injury, cumulative fluid balance >2.5 L for 24 hours, lactate levels, and vasopressor use (adjusted odds ratio: 2.953, 2.058, 1.170, and 2.910; 95% confidence interval: 1.410-6.181, 1.017-4.164, 1.019-1.343, and 1.414-5.987; P = .004, .045, .026, and .004, respectively) as independent risk factors for AKI.AKI in patients admitted to the ICU with torso injury had a substantial mortality. Recognizing risk factors at an early stage could aid risk stratification and provision of optimal ICU care.


cIAP1/2-TRAF2-SHP-1-Src-MyD88 Complex Regulates Lipopolysaccharide-Induced IL-27 Production through NF-κB Activation in Human Macrophages.
The inhibitors of apoptosis (IAP) proteins, initially described in the context of apoptosis regulation as promoting cell survival, have recently emerged as key regulators of innate immune signaling. As a result, downregulation of IAP via Smac mimetics (SMM) has both survival and immunoregulatory effects. IAPs modulate cytokine production in murine models either as a single agent or in response to LPS. However, the role of SMM and the involvement of IAPs in primary human cells and in particular macrophages with respect to cytokine production and innate immune responses remain largely unknown. IL-27, a member of the IL-12 cytokine family produced by APCs such as macrophages, has broad immunoregulatory properties in both innate and adaptive immune responses. Herein, we show that cellular IAPs (cIAPs) positively regulate LPS-induced IL-27 production in both primary human monocytes and macrophages. Investigations for the signaling mechanism of cIAPs involvement in IL-27 production in human macrophages revealed that LPS-induced IL-27 production is regulated by a novel signaling complex comprising cIAP1/2, TNFR-associated factor 2 (TRAF2), SHP-1, Src, and MyD88 leading to p38, c-Jun N-terminal kinases (JNK) and Akt activation and NF-κB signaling. In cancer cells, SMM induce the production of cytokines by activating the noncanonical alternate NF-κB pathway. However, in human macrophages, SMM do not induce the production of TNF-α and other cytokines while inhibiting LPS-induced IL-27 production by inhibiting the classical NF-κB pathway. These signaling pathways may constitute novel therapeutic avenues for immune modulation of IL-27 and provide insight into the modulatory immune effects of SMM.


Optimizing the Agrobacterium tumefaciens-mediated transformation conditions in Colletotrichum lindemuthianum: a step forward to unravel the functions of pathogenicity arsenals.
Colletotrichum lindemuthianum is a hemibiotrophic fungal pathogen that causes bean anthracnose and it is rated among the top 10 important diseases infecting beans. Currently our knowledge on molecular mechanisms underlying C. lindemuthianum pathogenesis is limited. About five pathogenicity genes have been identified in C. lindemuthianum using Restricted Enzyme Mediated Integration and the transformation using Agroinfection has not been optimized. In this study, a series of experiments were conducted to optimize the key parameters affecting the Agrobacterium tumefaciens-mediated transformation for C. lindemuthianum. The transformation efficiency increased with increase in spore concentration and co-cultivation time. However, the optimum conditions that yielded significant number of transformants were 106 ml-1 spore concentration, co-cultivation time of 72 h, incubation at 25°C and using a cellulose membrane filter for the co-cultivation. The optimized protocol resulted in establishment of large mutant library (2400). A few mutants were melanin deficient and a few were unable to produce conidia. To determine the altered pathogenicity, two new approaches such as detached leaf and twig techniques proved reliable and require fewer resources to screen the large mutant libraries in a short time. Among the 1200 transformants tested for virulence, 90% transformants were pathogenically similar to wild type (race 2047), 96 and 24 were reduced and impaired, respectively. The altered avirulent transformants can prove vital for understanding the missing link between growth and developmental stages of pathogen with virulence. This platform will help to develop strategies to determine the potential pathogenicity genes and to decipher molecular mechanisms of host-pathogen interactions in more detail.


Introduction: A focus on the medical management of endometriosis.
In this views and reviews series of articles, we focus on the long-term medical management of endometriosis in lieu of surgery. The development of noninvasive biomarkers will facilitate the early diagnosis of endometriosis and early medical management. We discuss the use of oral progestin-only as first line treatment in place of oral contraceptives. Future medical treatments may be curative rather than simply suppressive or palliative. The section on surgery mainly pertains to failed medical management or specific types of endometriosis which require surgical excision.


Smart Capsules for Lead Removal from Industrial Wastewater.
Ground and especially drinking water could be contaminated by heavy metal ions such as lead and chromium, or the metalloid arsenic, discarded from industrial wastewater. These heavy metal ions are regarded as highly toxic pollutants which could cause a wide range of health problems in case of a long-term accumulation in the body. Thus, there have been many efforts to reduce the concentration of lead ions in effluent wastewater. They have included the establishment of stringent permissible discharge levels and management policies, the application of various pollution-control technologies, and the development of adsorbent materials for lead reduction. According to Science [1] encapsulation, developed approximately 65 years ago, has been defined as a major interdisciplinary research technology. Encapsulation has been used to deliver almost everything from advanced drugs to unique consumer sensory experiences. In this chapter we review the art of encapsulation technology as a potential breakthrough solution for a recyclable removal system for lead ions. Moreover, in order to provide the readers with a comprehensive and in-depth understanding of recent developments and innovative applications in this field, we highlight some remarkable advantages of encapsulation for heavy metal remove, such as simplicity of preparation, applicability for a wide range of selective extractants, large special interfacial area, ability for concentration of metal ions from dilute solutions, and less leakage of harmful components to the environment.


Pathways to improved radiologic research. An NIH workshop.
In summary, the workshop recommended two years of research training as being essential for radiologists to acquire the skills and knowledge necessary to begin a successful research career in today's funding and academic environment. Many pathways can combine two years of research training and provide fulfillment of existing requirements to achieve specialty certification and subspecialty credentialing. Departments of radiology supporting the beginning qualified investigator should allow him or her approximately 75% research time for the first three years of the academic appointment. Departmental research time accorded faculty members may best be concentrated on a few individuals, providing them sufficient time to be competitive for peer-reviewed grants and enabling research advances to provide a solid foundation for the future of radiologic imaging.


Effects of pacemaker currents on creation and modulation of human ventricular pacemaker: theoretical study with application to biological pacemaker engineering.
A cardiac biological pacemaker (BP) has been created by suppression of the inward rectifier K(+) current (I(K1)) or overexpression of the hyperpolarization-activated current (I(h)). We theoretically investigated the effects of incorporating I(h), T-type Ca(2+) current (I(Ca,T)), sustained inward current (I(st)), and/or low-voltage-activated L-type Ca(2+) channel current (I(Ca,LD)) on 1) creation of BP cells, 2) robustness of BP activity to electrotonic loads of nonpacemaking (NP) cells, and 3) BP cell ability to drive NP cells. We used a single-cell model for human ventricular myocytes (HVMs) and also coupled-cell models composed of BP and NP cells. Bifurcation structures of the model cells were explored during changes in conductance of the currents and gap junction. Incorporating the pacemaker currents did not yield BP activity in HVM with normal I(K1) but increased the critical I(K1) conductance for BP activity to emerge. Expressing I(h) appeared to be most helpful in facilitating creation of BP cells via I(K1) suppression. In the coupled-cell model, I(st) significantly enlarged the gap conductance (G(C)) region where stable BP cell pacemaking and NP cell driving occur, reducing the number of BP cells required for robust pacemaking and driving. In contrast, I(h) enlarged the G(C) region of pacemaking and driving only when I(K1) of the NP cell was relatively low. I(Ca,T) or I(Ca,LD) exerted effects similar to those of I(st) but caused shrinkage or irregularity of BP oscillations. These findings suggest that expressing I(st) most effectively improves the structural stability of BPs to electrotonic loads and the BP ability to drive the ventricle.


Bulk, surface and point defect properties in UO2 from a tight-binding variable-charge model.
A tight-binding variable-charge model (SMTB-Q) has been used to calculate bulk, surface and point defect properties in uranium dioxide. It provides us with a better description of the iono-covalent oxides than classical, purely ionic models. A good agreement is found in the structural properties and cohesive energy between the model and experimental data; the charges calculated on the uranium and oxygen ions are Q(U) = 2.804 and Q(O) =- 1.402 respectively. The stability and relaxation of low index surfaces were evaluated: the (111) surface consistently has the lowest surface energy and the smallest surface relaxation, followed by the (110) surface and the (100) surface, in agreement with previous predictions from semi-empirical potentials and from ab initio calculations. The energy ranking of intrinsic defects is oxygen Frenkel pair < Schottky trio < uranium Frenkel pair, which is consistent with literature. The clustering energy of small vacancy clusters has been also calculated. Additionally, the atomic relaxations and the charge transfer at surfaces and around defects have been investigated. All the results obtained in the present work prove the ability of the SMTB-Q model to describe the bulk properties as well as the surface and defect properties in uranium dioxide. Finally, this model provides us with a new fundamental insight into the role played by the charge transfer in UO2 properties.


Subtle developmental abnormalities in the inferior olive: an indicator of prenatal brainstem injury in the sudden infant death syndrome.
Subtle quantitative abnormalities in neuronal populations derived from the rhombic lip (i.e. arcuate nucleus at the ventral medullary surface, external granular layer of the cerebellum) have been reported in victims of the sudden infant death syndrome (SIDS). In this study, we examined the inferior olive, a major rhombic lip derivative, to determine if subtle rhombic lip abnormalities also involve this nucleus in SIDS. We analyzed the number and density of neurons and reactive astrocytes in the inferior olive in 29 SIDS cases and 29 controls. Computer-assisted cell counting procedures were used in sections stained with hematoxylin and eosin/Luxol fast blue. There was a significant difference in the postconceptionally age-adjusted mean for neuronal density between SIDS cases (7,687 +/- 255 neurons/mm(3)) and controls (8,889 +/- 255 neurons/mm(3)) (p = 0.002). The difference in age-adjusted mean neuronal number between SIDS cases (1,932 +/- 89 neurons/2 sections) and controls (2,172 +/- 89 neurons/2 sections) was marginally significant (p = 0.063). Reactive astrocytes were present in the inferior olive in SIDS cases, but their number, density, and developmental profile were not significantly different from that of control infants dying of diverse known causes. SIDS victims found dead in cribs, beds, and sofas, prone or supine had subtle olivary abnormalities, suggesting that affected infants are at risk in various sleeping situations. We propose that at least some SIDS victims experience intrauterine brainstem injury including the olivo-arcuato-cerebellar circuitry derived from the rhombic lip. These observations provide future directions for SIDS research concerning the role of early insults in pregnancy, the rhombic lip, and the interactions of the ventral medulla and cerebellum in cardioventilatory control.


Reversed-phase high-performance liquid chromatographic prefractionation of immunodepleted human serum proteins to enhance mass spectrometry identification of lower-abundant proteins.
Serum analysis represents an extreme challenge due to the dynamic range of the proteins of interest, and the high structural complexity of the constituent proteins. In serum, the quantities of proteins and peptides of interest range from those considered "high abundance", present at 2-70% by mass of total protein, to those considered "low abundance", present at 10(-12) M or less. This range of analytical target molecules is outside the realm of available technologies for proteomic analysis. Therefore, in this study, we have developed a workflow toward addressing the complexity of these samples through the application of multidimensional separation techniques. The use of reversed-phase methods for the separation and fractionation of protein samples has been investigated, with the goal of developing an optimized serum separation for application to proteomic analysis. Samples of human serum were depleted of the six most abundant proteins, using an immunoaffinity LC method, then were separated under a variety of reversed-phase (RP) conditions using a macroporous silica C18 surface modified column material. To compare the qualities of the RP separations of this complex protein sample, absorbance chromatograms were compared, and fractions were collected for off-line SDS-PAGE and 2D-LC-MS/MS analysis. The column fractions were further investigated by determination of protein identities using either whole selected fractions, or gel bands excised from SDS-PAGE gels of the fractions. In either case samples underwent tryptic fragmentation and peptide analysis using MALDI-MS or LC-MS/MS. The preferred conditions for RP protein separation exhibited reproducibly high resolution and high protein recoveries (>98%, as determined by protein assay). Using the preferred conditions also permitted high column mass load, with up to 500 microg of protein well tolerated using a 4.6 mm ID x 50 mm column, or up to 1.5 mg on a 9.4 mm ID x 50 mm column. Elevated column temperature (80 degrees C) was observed to be a critical operational parameter, with poorer results observed at lower temperatures. The combination of sample simplification by immunoaffinity depletion combined with a robust and high recovery RP-HPLC fractionation yields samples permitting higher quality protein identifications by coupled LC-MS methods.


Electroencephalographic monitoring in the pediatric intensive care unit.
Continuous electroencephalographic (CEEG) monitoring is used with increasing frequency in critically ill children to provide insight into brain function and to identify electrographic seizures. CEEG monitoring use often impacts clinical management, most often by identifying electrographic seizures and status epilepticus. Most electrographic seizures have no clinical correlate, and thus would not be identified without CEEG monitoring. There are increasing data showing that electrographic seizures and electrographic status epilepticus are associated with worse outcome. Seizure identification efficiency may be improved by further development of quantitative electroencephalography trends. This review describes the clinical impact of CEEG data, the epidemiology of electrographic seizures and status epilepticus, the impact of electrographic seizures on outcome, the utility of quantitative electroencephalographic trends for seizure identification, and practical considerations regarding CEEG monitoring.


Gamma-Fe2O3 nanopowders synthesized in microwave plasma and extraordinarily strong temperature influence on their Mössbauer spectra.
The article reports on two nanopowders synthesized in microwave plasma: the first sample was synthesized in a torch discharge at 1 bar and the second sample was synthesized in low-pressure plasma at 40 mbar. Morphology, composition and properties of the powders were studied by TEM, XRD, Raman and Mössbauer spectroscopies, and magnetic measurements. In the XRD patterns of the samples only gamma-Fe2O3 was identified (mean crystallite size d(XRD) was 24 nm for the first sample and 13 nm for the second sample). Based on the Mössbauer spectra measured at 5 K, the presence of other iron oxide phases was excluded in both samples. Unusually strong temperature dependence of the Lamb-Mössbauer factor was observed: I(SA)(5 K)/I(SA)(293 K) = 6 in the case of the first sample and I(SA)(5 K)/I(SA)(293 K) = 22 for the second sample (I(SA) denotes integral spectrum area). This effect is explained as the consequence of the reduced agglomeration of electrically charged nanoparticles in the plasma, i.e., particles can either move at 293 K (when they are free) or tilt (if they are a part of a chain). Superparamagnetic phase was not observed in the room-temperature Mössbauer spectra of both samples.


Sugar-sweetened beverage purchases and intake at event arenas with and without a portion size cap.
This is the first real-world study to examine the association between a voluntary 16-ounce (oz) portion-size cap on sugar-sweetened beverages (SSB) at a sporting arena on volume of SSBs and food calories purchased and consumed during basketball games. Cross-sectional survey data from adults exiting a Brooklyn, NY, USA arena (Barclays, n = 464) with a 16-oz portion-size restriction and a Manhattan, NY, USA arena with no portion-size restriction (Madison Square Garden, control, n = 295) after the portion cap policy was put in place from March through June 2014 were analyzed. Linear regression models adjusting for sex, age, BMI, ethnicity, race, marital status, education, and income were used to compare the two arenas during the post-implementation period. The survey response rate was 45.9% and equivalent between venues. Among all arena goers, participants at Barclays purchased significantly fewer SSB oz (-2.24 oz, 95% CI [-3.95, -0.53], p = .010) and consumed significantly fewer SSB oz (-2.34 oz, 95% CI[-4.01, -0.68], p = .006) compared with MSG after adjusting for covariates. Among those buying at least one SSB, Barclays' participants purchased on average 11.03 fewer SSB oz. (95% CI = [4.86, 17.21], p < .001) and consumed 12.10 fewer SSB oz (95% CI = [5.78, 18.42], p < .001). There were no statistically significant differences between arenas in food calories and event satisfaction. In addition, no one reported not ordering a drink due to small size. An SSB portion-size cap was associated with purchasing and consuming fewer SSB oz. without evidence of decreasing satisfaction with the event experience.


Automatic wheat ear counting using machine learning based on RGB UAV imagery.
In wheat (Triticum aestivum L) and other cereals, the number of ears per unit area is one of the main yield-determining components. An automatic evaluation of this parameter may contribute to the advance of wheat phenotyping and monitoring. There is no standard protocol for wheat ear counting in the field, and moreover it is time consuming. An automatic ear-counting system is proposed using machine learning techniques based on RGB (red, green, blue) images acquired from an unmanned aerial vehicle (UAV). Evaluation was performed on a set of 12 winter wheat cultivars with three nitrogen treatments during the 2017-2018 crop season. The automatic system uses a frequency filter, segmentation and feature extraction, with different classification techniques, to discriminate wheat ears in micro-plot images. The relationship between the image-based manual counting and the algorithm counting exhibited high levels of accuracy and efficiency. In addition, manual ear counting was conducted in the field for secondary validation. The correlations between the automatic and the manual in-situ ear counting with grain yield were also compared. Correlations between the automatic ear counting and grain yield were stronger than those between manual in-situ counting and GY, particularly for the lower nitrogen treatment. Methodological requirements and limitations are discussed.


Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients.
In hepatitis B "e" antigen (HBeAg) positive patients with hepatitis B virus (HBV) mono-infection, intensification of nucleos(t)ide analogue treatment with pegylated interferon (PegIFN) could help induce higher HBeAg seroclearance rates. Our aim was to determine the long-term effect of adding PegIFN to tenofovir (TDF)-containing antiretroviral therapy on seroclearance in HBeAg-positive patients co-infected with the human immunodeficiency virus (HIV) and HBV. In this prospective matched cohort study, 46 patients with 1-year PegIFN intensification during TDF-containing antiretroviral therapy (TDF+PegIFN) were matched 1:1 to controls undergoing TDF without PegIFN (TDF) using a time-dependent propensity score based on age, CD4+ count and liver cirrhosis status. Kinetics of HBeAg quantification (qHBeAg) and hepatitis B surface antigen quantification (qHBsAg) were estimated using mixed-effect linear regression and time to HBeAg seroclearance or HBsAg seroclearance was modelled using proportional hazards regression. At baseline, previous TDF exposure was a median 39.8 months (IQR=21.4-59.4) and median qHBeAg and qHBsAg levels were 6.9 PEIU/mL and 3.72 log10 IU/mL, respectively (P>.5 between groups). Median follow-up was 33.4 months (IQR=19.0-36.3). During intensification, faster average declines of qHBeAg (-0.066 vs -0.027 PEIU/mL/month, P=.001) and qHBsAg (-0.049 vs -0.026 log10 IU/mL/month, P=.09) were observed in patients undergoing TDF+PegIFN vs TDF, respectively. After intensification, qHBeAg and qHBsAg decline was no different between groups (P=.7 and P=.9, respectively). Overall, no differences were observed in HBeAg seroclearance (TDF+PegIFN=13.2 vs TDF=12.6/100 person·years, P=.5) or HBsAg seroclearance rates (TDF+PegIFN=1.8 vs TDF=1.3/100 person·years, P=.7). In conclusion, PegIFN intensification in HBeAg-positive co-infected patients did not lead to increased rates of HBeAg or HBsAg clearance, despite faster declines of antigen levels while on PegIFN.


Use of an axial pattern flap and nictitans to reconstruct medial eyelids and canthus in a dog.
A 10-year-old male neutered Boxer presented with recurrence of a mast cell tumor at the right medial canthal area. Following excision including 2 cm margins, the medial one-half of the upper and lower eyelids and the medial canthus were reconstructed using an axial pattern flap based on the cutaneous branch of the superficial temporal artery. The bulbar conjunctiva of the nictitans was preserved and sutured to the medial flap edge, thus creating a conjunctival lining to the deep aspect of the flap, protecting corneal epithelium. This is a valuable surgical technique for closing a large skin defect and reconstructing the medial eyelids, thus preserving the globe.


Expression of the 1Ax1 transgene in an elite Chinese wheat variety and its effect on functional properties.
The transfer of transgenes from 'model' wheat genotypes into elite wheat cultivars using conventional plant breeding is an alternative strategy for improving the dough quality of wheat. Thus a cross was made between a popular Chinese elite wheat cultivar of the Yangzi River down-central area that expresses high-molecular-weight glutenin subunit (HMW-GS): 1Bx7 + 1By8 plus 1Dx2 + 1Dy12, and a model transgenic wheat line B102-1-2 which over-expresses HMW-GS 1Ax1 in an L88-31 genetic background that includes HMW-GS 1Bx17 + By18. F(1) to F(6) generations of crosses between B102-1-2 (paternal) and Emai (maternal) were analysed for their HMW-GS compositions, allowing the selection of pure F(6) lines over-expressing HMS-GS 1Ax1 in the presence of the endogenous HMW-GS: 1Bx7 + 1By8 with 1Dx2 + 1Dy12, and 1Bx17 + 1By18 with 1Dx2 + 1Dy12. Analysis of the F(6) lines showed changes in the extensograph parameters, with increases in peak area, resistance to extension, and extensibility and peak resistance to extension, similar to those observed in the transgenic paternal line B102-1-2. This work showed that the expression levels of the 1Ax1 transgene and the effects on dough properties were similar in the transgenic parental line B102-1-2 and the F(6) progeny generated from a cross with an elite Chinese cultivar Emai. The feasibility of using transgenic lines expressing HMW-GS subunits in conventional breeding programmes was demonstrated.


Fractal heterogeneous media.
A method is presented for generating compact fractal disordered media by generalizing the random midpoint displacement algorithm. The obtained structures are invasive stochastic fractals, with the Hurst exponent varying as a continuous parameter, as opposed to lacunar deterministic fractals, such as the Menger sponge. By employing the detrending moving average algorithm [A. Carbone, Phys. Rev. E 76, 056703 (2007)], the Hurst exponent of the generated structure can be subsequently checked. The fractality of such a structure is referred to a property defined over a three-dimensional topology rather than to the topology itself. Consequently, in this framework, the Hurst exponent should be intended as an estimator of compactness rather than of roughness. Applications can be envisaged for simulating and quantifying complex systems characterized by self-similar heterogeneity across space. For example, exploitation areas range from the design and control of multifunctional self-assembled artificial nanostructures and microstructures to the analysis and modeling of complex pattern formation in biology, environmental sciences, geomorphological sciences, etc.


First record of Trochochaeta japonica (Annelida: Spionidae) in Brazil with identification key to species of the genus.
Polychaetes of the spionid genus Trochochaeta occur mainly in the northern hemisphere, including North and Central America. In South America, they have been reported only from the northeast region of Brazil - Sergipe and Paraíba - despite numerous biological investigations around the continent. In 2006, a dense population (up to 7000 individuals per square meter) of Trochochaeta was discovered in the estuary of Santos, São Paulo, Brazil, hosting the busiest container sea port in Latin America, and in 2008, one Trochochaeta specimen was found in Camamu Bay, Bahia. We identify these worms as Trochochaeta japonica Imajima, 1989 and describe and illustrate their morphology. This is the first record of the species from outside of its type locality in Honshu, Japan. It might have been introduced to the estuary of Santos as larvae in ballast water of ocean-going vessels. We review the systematics of Trochochaeta and provide an identification key to 12 currently recognized species.


Pneumocystis Carinii pneumonia in an AIDS patient with dramatic response to inadvertent steroid therapy--a case report.
A 28 year-old homosexual man had one month history of intermittent high fever, nonproductive cough and progressive shortness of breath. He not only had immunity deficits, with decrease CD4 cells decreased CD8 cells and inverted CD4/CD8 ratio, but also presented with evidence of human immunodeficiency virus infection (positive ELISA antibody tests and Western blot tests). Chest X-ray showed diffuse pulmonary infiltration. The arterial blood gases revealed hypoxemia. The PaO2 was 69 mmHg. Spirometry showed FVC 2.28 L (45% predicted), FEV1 2.21 L (49% predicted), FEV1/FVC 93%, and MMEF 4.41 L/sec (90% predicted). The configuration of the Flow-Volume loop was consistent with a restrictive ventilatory defect. Transthoracic lung biopsy demonstrated pneumocystis carinii pneumonia (PCP). He had inadvertent steroid therapy and showed some clinical, pulmonary function and chest X-ray improvement before the diagnosis was established. Steroids might be as adjunctive therapy for a short period of time in treatment of PCP associated with acquired immunodeficiency syndrome (AIDS) at respiratory failure.


Phylogenetic and functional classification of mitogen- and stress-activated protein kinases.
All currently sequenced stress-activated protein kinases (SAPKs), extracellular signal-regulated kinases (ERKs), and other mitogen-activated protein kinases (MAPKs) were analyzed by sequence alignment, phylogenetic tree construction, and three-dimensional structure modeling in order to classify members of the MAPK family. Based on this analysis the MAPK family was divided into three subgroups (SAPKs, ERKs, and MAPK3) that consist of at least nine subfamilies. Members of a given subfamily were exclusively from animals, plants, or yeast/fungi. A single signature sequence, [LIVM][TS]XX[LIVM]XT[RK][WY]YRXPX[LIVM] [LIVM], was identified that is characteristic for all MAPKs and sufficient to distinguish MAPKs from other members of the protein kinase superfamily. This signature sequence contains the phosphorylation site and is located on loop 12 of the three-dimensional structure of MAPKs. I also identified signature sequences that are characteristic for each of the nine subfamilies of MAPKs. By modeling the three-dimensional structure of three proteins for each MAPK subfamily based on the resolved atomic structures of rat ERK2 and murine p38, it is demonstrated that amino acids conserved in all MAPKs are located primarily in the center of the protein around the catalytic cleft. I conclude that these residues are important for maintaining proper folding into the gross structure common to all MAPKs. On the other hand, amino acids conserved in a given subfamily are located mainly in the periphery of MAPKs, indicating their possible importance for defining interactions with substrates, activators, and inhibitors. Within these subfamily-specific regions, amino acids were identified that represent unique residues occurring in only a single subfamily and their location was mapped in three-dimensional structure models. These unique residues are likely to be crucial for subfamily-specific interactions of MAPKs with substrates, inhibitors, or activators and, therefore, represent excellent targets for site-directed mutagenesis experiments.


Changes in physical function in older women with endometrial cancer with or without adjuvant therapy.
To evaluate changes in physical function (PF) for older women with endometrial cancer (EC) + / - adjuvant therapy in the Women's Health Initiative Life and Longevity after Cancer cohort. This study examined women ≥ 70 years of age with EC with available treatment records. Change in PF was measured using the RAND-36 and compared between groups using Wilcoxon rank-sum tests. Multivariable median regression was used to compare the changes in scores while adjusting for confounding variables. Included in the study were 287 women, 150 (52.3%) women who did not receive adjuvant therapy and 137 (47.7%) who received adjuvant therapy. When comparing PF scores, there was a statistically significant difference in the median percent change in functional decline, with a greater decline in those who received adjuvant therapy (- 5.9% [- 23.5 to 0%]) compared to those who did not (0 [- 18.8 to + 6.7%]), p = 0.02). Results were not statistically significant after multivariable adjustment, but women who underwent chemotherapy had a greater percent change (median ∆ - 13.8% [- 35.5 to 0%]) compared to those who received radiation alone (median ∆ - 5.9% [- 31.3 to 0%]) or chemotherapy and radiation (median ∆ - 6.5% [- 25.8 to + 5.7%]. Older women with EC who received adjuvant therapy experienced greater change in PF than those who did not receive adjuvant therapy, particularly women who received chemotherapy. These results were not statistically significant on multivariate analysis. EC survivors may experience changes in PF because of chemotherapy and/or radiation therapy. Additional supportive care may need to be provided to older women to mitigate functional decline.


Development and partial validation of a mouse model for predicting drug hypersensitivity reactions.
Animal models that can be used to predict the allergenic potential of drug candidates have not been adequately optimized, validated, or characterized. While initial validation data from an inter-laboratory study of the mouse lymph node proliferation assay (LNPA) appeared promising, no additional investigations in this model have been reported. The objectives of this study were to use positive and negative control drugs to further optimize and validate the LNPA utilizing a non-radioactive endpoint and determine the sensitivity, specificity, and predictivity of the model. Drugs associated with hypersensitivity reactions in the literature were chosen to test in the model in addition to drugs with few or no reports of hypersensitivity. Mice received a subcutaneous injection of drug or vehicle into the scruff of the neck once daily for a period of 3 days. On Day 6, draining lymph nodes were harvested, single cell suspensions prepared, and total cell numbers determined for each animal by flow cytometry. A stimulation index was calculated by dividing the mean total cell number for the drug-treated group by the mean total cell number for the vehicle-treated animals. Based on statistical analysis of the data, animals with a total cell number ≥2.5× the mean of the vehicle group were classified as 'responders'. Based on data generated to date with 12 positive control and six negative control drugs, the model had a sensitivity of 75%, a specificity of 74%, and a relatively good predictive value (measured by the Receiver Operating Characteristic AUC of 0.80). The data here suggest that this model may be a useful tool for identifying drug candidates with the potential to produce allergic responses in the clinic. Future studies will investigate the mechanism(s) for the lymph node responses in order to develop additional endpoints that may increase the sensitivity and specificity of the model.


11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Development by Lentiviral Screening Based on Computational Modeling.
In this study, rat and human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been cloned by lentiviral transduction and expressed by CHO-K1 cells. The results showed that recombinant plasmids contained R11bhsd1 or H11bhsd1 have been constructed, which is consistent with the gene bank respectively. A clone cell was selected with G418 and cultivated to express 11β-HSD1. 11β-HSD1 catalytic activity of rat and human were 99.5 and 98.7%, respectively, determined by scanning radiometer. And the cloned CHO-K1 cells expressed the protein of 11β-HSD1 in a long-term and stable manner, which makes it suitable for screening 11β-HSD1 inhibitor. The three-dimensional structure of 11β-HSD1 was used for studying the interaction between inhibitor and enzyme by the binding poses predicted by AutoDock and LeDock software. The docking results revealed that compound 8 forms 2 hydrogen bonds with the residues of Gly-216 and Ile-218 in 11β-HSD1, that is to say compound 8 maybe a good 11β-HSD1 inhibitor. Moreover, C57BL/6 mice with R11bHsd1 overexpression had a higher body weight, glucose, total cholesterol, and triglyceride levels compared to the mice treated with an empty viral vector. The results might provide a beneficial foundation for selecting inhibitors of 11β-HSD1 or for researching drug candidate mechanisms.


Expression of beta-catenin and gamma-catenin in epithelial tumor cell lines and characterization of a unique cell line.
In addition to its structural role, beta-catenin has recently been identified as an oncogene, while its homologue gamma-catenin (plakoglobin) seems to suppress tumorigenicity. Twenty-five epithelial tumor cell lines were screened; 18 expressed both beta- and gamma-catenin, two expressed neither protein, four showed beta- but not gamma-catenin expression, while only one cell line showed gamma- but not beta-catenin expression. As per literature search, the cell line expressing gamma- but not beta-catenin appeared to be unique. This cell line, SKBR-3, is a human breast cancer cell line which does not express beta-catenin or E-cadherin protein. There is, however, expression of beta-catenin, but not E-cadherin, mRNA. In order to determine the mechanism for this unique expression pattern, SKBR-3 cells were transfected with E-cadherin which resulted in expression of beta-catenin protein. Immunofluorescent staining of the E-cadherin transfected SKBR-3 cells revealed beta-catenin in the adherens junctions while transfection with just an epitope tagged (VSV) beta-catenin showed expression only in the nucleus. Double transfection with E-cadherin and VSV beta-catenin showed the beta-catenin in the adherens junction of the E-cadherin transfected cells. These results indicate that the mechanism for the lack of beta-catenin expression in the SKBR-3 cell line is possibly post-translational degradation and that when E-cadherin is transfected into these cells, the beta-catenin is stabilized in the adherens junction and not degraded. This cell line should be of interest to those studying the role of the homologues, beta- and gamma-catenin, in cancer pathogenesis.


Sex hormones and the QT interval: a review.
A prolonged QT interval is a marker for an increased risk of ventricular tachyarrhythmias. Both endogenous and exogenous sex hormones have been shown to affect the QT interval. Endogenous testosterone and progesterone shorten the action potential, and estrogen lengthens the QT interval. During a single menstrual cycle, progesterone levels, but not estrogen levels, have the dominant effect on ventricular repolarization in women. Studies of menopausal hormone therapy (MHT) in the form of estrogen-alone therapy (ET) and estrogen plus progesterone therapy (EPT) have suggested a counterbalancing effect of exogenous estrogen and progesterone on the QT. Specifically, ET lengthens the QT, whereas EPT has no effect. To date, there are no studies on oral contraception (OC) and the QT interval, and future research is needed. This review outlines the current literature on sex hormones and QT interval, including the endogenous effects of estrogen, progesterone, and testosterone and the exogenous effects of estrogen and progesterone therapy in the forms of MHT and hormone contraception. Further, we review the potential mechanisms and pathophysiology of sex hormones on the QT interval.


A 4K-Input High-Speed Winner-Take-All (WTA) Circuit with Single-Winner Selection for Change-Driven Vision Sensors.
Winner-Take-All (WTA) circuits play an important role in applications where a single element must be selected according to its relevance. They have been successfully applied in neural networks and vision sensors. These applications usually require a large number of inputs for the WTA circuit, especially for vision applications where thousands to millions of pixels may compete to be selected. WTA circuits usually exhibit poor response-time scaling with the number of competitors, and most of the current WTA implementations are designed to work with less than 100 inputs. Another problem related to the large number of inputs is the difficulty to select just one winner, since many competitors may have differences below the WTA resolution. In this paper, a WTA circuit is presented that handles more than four thousand inputs, to our best knowledge the hitherto largest WTA, with response times below the microsecond, and with a guaranty of just a single winner selection. This performance is obtained by the combination of a standard analog WTA circuit and a fast digital single-winner selector with almost no size penalty. This WTA circuit has been successfully employed in the fabrication of a Selective Change-Driven Vision Sensor based on 180 nm CMOS technology. Both simulated and experimental results are presented in the paper, showing that a single pixel event can be selected in just 560 ns, and a multipixel pixel event can be processed in 100 us. Similar results with a conventional approach would require a camera working at more than 1 Mfps for the single-pixel event detection, and 10 kfps for the whole multipixel event to be processed.


Hypoglycaemia in an inner-city accident and emergency department: a 12-month survey.
In a 12-month survey on the causes and frequency of hypoglycaemia presenting to an inner-city accident and emergency department, a total of 86 cases were recorded. A missed meal and/or alcohol ingestion accounted for most of the precipitating causes, being 52% and 21% respectively. As 49% of subjects presented with major clinical manifestations of hypoglycaemia (fit or coma), greater emphasis is required in the instruction on regularity of meal and caution with alcohol in high-risk groups such as the diabetic and also in non-diabetic groups.


[A Study on the Chinese Name of Smallpox].
The Zhou hou fang (Handbook of Formulae) is the earliest known ancient medical book carrying the title of smallpox, called "lu chuan" (captive sore). Since then, various names had been applied to this disorder, including "sheng chuang" (holy sore), "tian chuang" (celestial sore), "wan dou chuang" (pea sore), "fu dou chuang" (bran sore), and "dou zhen" (pox-rash). This frequent changes of disease titles in its history is a significant mark of the evolution of TCM recognition on smallpox related to its treatment and prevention, and folk-social customs. It was not until the Republican period that the title of "pox-rash" was substituted by smallpox, a specific title for this viral infection. This is also the outcome showing the important position of TCM treatment and prevention for smallpox replaced by the preventive method of modern smallpox vaccination.


[Results of the marketing research study "Acceptance of physician's office computer systems"].
We report on a market research study on the acceptance of computer systems in surgeries. 11,000 returned questionnaires of surgeons--user and nonuser--were analysed. We found out that most of the surgeons used their computers in a limited way, i.e. as a device for accounting. Concerning the level of utilisation there are differentials of Men-Women, West-East and Young-Old. In this study we also analysed the computer using behaviour of gynaecologic surgeons. As a result two third of all nonusers are not intending to utilise a computer in the future.


[Three cases of aspiration caused by cerebrovascular disorder that were managed with total laryngectomy].
Total laryngectomy can be used to prevent aspiration pneumonia in patients with severe dysphagia, though caution is required with regard to the indications. In this paper, we describe 3 patients in whom severe dysphagia developed as a result of cerebrovascular disorders, and who repeatedly developed aspiration pneumonia. We managed them with total laryngectomy, and this has prevented aspiration pneumonia in all three. Oral feeding became possible in two of these patients, and home care became possible for one. This report includes a discussion based on the literature, and includes preoperative evaluation and indications for laryngectomy.


Lending a hand for laparoscopic distal pancreatectomy: the optimal approach?
Both minimally invasive surgery (MIS) and open approaches for distal pancreatectomy are acceptable. MIS options include total laparoscopic/robotic (TLR) and hand-assist laparoscopy (HAL). When considering safety profile and specimen quality, the optimal approach is unknown. Patients who underwent distal pancreatectomy from 2010-2018 at two major academic institutions were included. Converted procedures were categorized into final approach. Ninety-day perioperative/pathologic outcomes of MIS and open were compared. Subset analyses between TLR vs HAL and HAL vs open were performed. Intent-to-treat analysis was performed. Among 1006 patients, resection was performed by MIS in 35% (n = 352), open in 65% (n = 654). MIS had similar patient comorbidity profile as open but had increased operative time (183 vs 162 min; p < 0.01), lower estimated-blood-loss (EBL; 131 vs 341 mL; p < 0.01), fewer intraoperative blood transfusions (1.4 vs 5%; p < 0.01), shorter LOS (5.2 vs 7.2 days; p < 0.01). Tumor size was smaller (3.2 vs 4.4 cm; p < 0.01) with lower lymph node (LN) yield (14 vs 16; p < 0.01). When comparing HAL (n = 109) to TLR (n = 243), despite increased prior abdominal operations (60 vs 43%; p = 0.008), HAL had shorter operative time (167 vs 191 min; p < 0.01), similar length-of-stay (LOS; 5.4 vs 5.1 days; p = 0.27), and readmission rate (15 vs 13%; p = 0.47). When comparing HAL to open, the advantages of TLR approach persisted including lower EBL (171 vs 342 mL; p < 0.01), and shorter LOS (5.4 vs 7.2 days; p < 0.01). Although HAL had smaller tumors, it had a similar LN yield (16 vs 16; p = 0.80), and higher R0-rate (97 vs 83%; p < 0.01). Hand-assist laparoscopy is safe and feasible for distal pancreatectomy as operative time, complication profile, lymph node yield, and R0-rates are similar to open procedures, while maintaining the associated the advantages of a total laparoscopic/robotic approach with reduced blood loss and shorter length-of-stay.


Ultra-high-pressure generation in the relativistic transparency regime in laser-irradiated nanowire arrays.
We show that an ultra-high-pressure plasma can be generated when an aligned nanowire is irradiated by a laser with relativistic transparent intensity. Using a particle-in-cell simulation, we demonstrate that the expanded plasma following the z pinch becomes relativistically transparent and compressed longitudinally by the oscillating component of the ponderomotive force. The compressed structure persists throughout the pulse duration with a maximum pressure of 40Tbar when irradiated with a laser at an intensity of 10^{23}Wcm^{-2}, 5× higher than the z-pinch pressure. These results suggest an alternative approach to extending the current attainable pressure in the laboratory.


Aggressive malignant phyllodes tumor of breast with omental metastases - A case report.
Distant metastasis from malignant Phyllodes tumour (PT) is rare. They generally metastasize to the lung, bone, pleura, and liver. We present a very rare case of a 25-year-old woman with intraabdominal metastases from malignant phyllodes tumour of the breast. She presented with left breast lump and the biopsy was Phyllodes tumour. She underwent a two staged surgery; left modified radical mastectomy followed by left latissimus dorsi musculocutaneous flap cover. She received adjuvant radiation therapy to left chest wall. Following which she developed intrabdominal mass which was proven to be metastasis from Phyllodes tumour. She was then advised palliative chemotherapy. Malignant Phyllodes with distant metastases has a dismal prognosis. We propose it is preferable to have a CT Thorax and Abdomen as a staging workup for patients with malignant PT to identify those with poor prognosis.


[Epidemiology and pathogenesis of Crohn's disease].
The onset of Crohn's disease (CD) is more frequent between 15 and 30 years and also has a second peak over 60 years. It female sex it is slightly more prevalent among female. Incidence rates vary in different geographic areas, ranging from 2 to 4 new cases/100,000 inhabitants/year. Prevalence data range from 1.2 to 200,000/100,000. Ethnic differences are beginning to disappear, underlining the role of environmental factors in the genesis of the disease. At the moment the most reliable hypothesis is that CD has a multifactorial pathogenesis: antigenic and environmental factors acting in genetically predisposed patients. According to this hypothesis, first degree relatives of CD patients have a relative risk of disease ranging from 2 to 4. Many infective agents have been associated with its onset and relapse; the most reliable observations are those related to the measles virus. There is an activation of the immunosystem which is shown by abnormal T-cell activation, by the increase of some cytokines and by the expression of adhesion molecules. The role of oral contraceptives and diet as risk factors is controversial. Smoking is the only risk factor positively associated with the onset of CD and its clinical course; this association is specific and dose-related.


Radiological analysis of swallowing and functional outcomes after hypopharyngo-laryngectomy with reconstruction using a jejunal autograft.
We report a distinct pattern of tongue movement. This is interpreted as a compensatory mechanism after hypopharyngo-laryngectomy with reconstruction using a jejunal autograft. Passage through the oesophagus is mainly passive. Swallowing is normally initiated voluntarily, and afterwards presumed to be controlled by brainstem reflexes. Resection of the hypopharynx with reconstruction may affect this control. This study attempted to perform a biomechanical analysis of the motility in the small bowel graft and suggest possible implications for surgical management. We also analysed how oesophageal passage is affected by surgery. Five patients underwent a radiological examination of the neopharyngeal conduit and oesophagus and completed a simple questionnaire. The radiological examinations revealed a distinct pattern of tongue movement in all patients, resulting in varying degrees of thrust. Passage through the jejunal graft was mainly passive, but observations of progressive reduction in diameter of the graft indicated muscular tone that may preserve pressure generated by the lingual thrust. The oesophageal transport appeared to be rather passive and largely depended upon the effect of gravity. Two of five patients were unable to eat normal food. Their impaired swallowing resulted in severely reduced quality of life.


Radioimmunoassay of bone marrow prostatic acid phosphatase.
The clinical value of prostate acid phosphatase (PAP) measurements in the bone marrow aspirate of patients with prostatic adenocarcinoma has been unclear. Using a radioimmunoassay (RIA) to measure PAP, we have evaluated this potential indicator of occult metastases in 127 controls and in 300 patients with prostatic adenocarcinoma. Elevations of the tumor marker were found in 9%, 10%, 19%, and 82% of patients with stages B, C, D1, and D2 adenocarcinoma respectively. Clinical follow-up ranging from 7 to 43 months (average 23 months) was available for 97 patients without any initial indication of metastasis by bone scan. In this group 11 patients had elevated levels of bone marrow acid phosphatase (BMAP) by RIA and four developed radiological evidence of bone metastasis 21-25 months following initial staging. However, only three of the 86 patients with normal BMAP levels have developed bone metastasis. Our results indicate that measurement of bone marrow PAP by immunological methods has prognostic significance. Dilution of the bone marrow aspirate by peripheral blood, however, may limit the application of this technique.


The Qa-1 alloantigens. I. Identification and molecular weight characterization of glycoproteins controlled by the Qa-1a and Qa-1b alleles.
Splenocytes from the Qa-Tla congenic strain pairs, A and A-Tlab or B6 and B6-Tlaa, were biosynthetically labeled with 3H-amino acids or cell surface labeled with 125I. Membrane proteins were solubilized with detergent and chromatographed on lentil lectin-Sepharose, and the resulting adherent pools were immunoprecipitated with antisera specific for determinants controlled by the Qa-1a and Qa-1b alleles, Qa-1.1 and Qa-1.2, respectively. Polyacrylamide gel electrophoresis analysis of immunoprecipitates from biosynthetically labeled preparations indicated that both the Qa-1.1 and Qa-1.2 antigens were glycoproteins with a m.w. of approximately 46,000. Qa-1.2 isolated from radioiodinated spleen cells similarly had a m.w. of 46,000. Analysis of anti-Qa-1.1 precipitates from 125I-labeled Qa-1a lysates demonstrated in addition to the 46,000 m.w. component, an electrophoretically heterogeneous protein or series of proteins in the m.w. range of 55,000 to 75,000. The specificity of these reactivities was shown by both antiserum and genetic control immunoprecipitations. These findings indicate that the Qa-1.1 and Qa-1.2 antigens are cell surface glycoproteins that are distinct from the TL antigens, and suggest a further complexity at the Qa-1--Tla locus.


Searching for the Holy Grail of Care Delivery Models.
Too often health care executives state the need for more research, knowledge, and information in staffing. Perhaps what we really need is education and support for innovation in operations. In looking for the holy grail of staffing solutions, focused attention will need to be placed on creating innovative care delivery models. Leaders who are tasked with developing innovative care delivery models must have a supportive environment and given time to be successful.


The left ventricle undergoes biomechanical and gene expression changes in response to increased right ventricular pressure overload.
Pulmonary hypertension (PH) results in right ventricular (RV) pressure overload and eventual failure. Current research efforts have focused on the RV while overlooking the left ventricle (LV), which is responsible for mechanically assisting the RV during contraction. The objective of this study is to evaluate the biomechanical and gene expression changes occurring in the LV due to RV pressure overload in a mouse model. Nine male mice were divided into two groups: (a) pulmonary arterial banding (PAB, N = 4) and (b) sham surgery (Sham, N = 5). Tagged and steady-state free precision cardiac MRI was performed on each mouse at 1, 4, and 7 weeks after surgery. At/week7, the mice were euthanized following right/left heart catheterization with RV/LV tissue harvested for histology and gene expression (using RT-PCR) studies. Compared to Sham mice, the PAB group revealed a significantly decreased LV and RV ejection fraction, and LV maximum torsion and torsion rate, within the first week after banding. In the PAB group, there was also a slight but significant increase in LV perivascular fibrosis, which suggests elevated myocardial stress. LV fibrosis was also accompanied with changes in gene expression in the hypertensive group, which was correlated with LV contractile mechanics. In fact, principal component (PC) analysis of LV gene expression effectively separated Sham and PAB mice along PC2. Changes in LV contractile mechanics were also significantly correlated with unfavorable changes in RV contractile mechanics, but a direct causal relationship was not established. In conclusion, a purely biomechanical insult of RV pressure overload resulted in biomechanical and transcriptional changes in both the RV and LV. Given that the RV relies on the LV for contractile energy assistance, considering the LV could provide prognostic and therapeutic targets for treating RV failure in PH.


Validity and Reliability of the Seizure Self-Efficacy Scale for Children with Epilepsy.
This study aims to adapt the Seizure Self-Efficacy Scale for Children (SSES-C) into Turkish and then assess its validity and reliability in children with epilepsy. The study sample consisted of 166 children (aged 9-17 years) with epilepsy who attended of Akdeniz University Hospital, Antalya Training and Research Hospital, and Bursa Dortcelik Children's Hospital Pediatric Neurology Clinics between July 2012 and March 2013. All research data were collected by a researcher in face-to-face interviews using Child Information Form, Seizure Self-Efficacy Scale for Children and Children's Depression Scale. The Seizure Self-Efficacy Scale for Children is a 15-item, 5-point Likert scale designed by Caplin et al. (2002). The linguistic adaptation and validation of the scale was conducted by seven experts. To evaluate the content validity of the scale, we elicited judgments from a panel of 10 content experts. The expert judgments showed that the correlation between the items on the scale was fairly good (Kendall's W=0.411, p<0.001, ki-kare: 57.495). Load factor of 40% and a large factor analysis included analysis of substances and two factors accounting for 49.67% of the total variance explained. We calculated Cronbach's alpha coefficient for the internal consistency and the full-scale score showed good internal consistency (alpha 0.89). Within the context of reliability studies, it was found correlations varying between 0,98-0,74 for the two sub-factors of the scale. Test/retest correlation coefficients were significant (p<0,01) and high (r=0.99). In parallel forms reliability, the correlations between the Seizure Self-Efficacy Scale for Children and Children's Depression Rating Scale were found to be negative, moderate and statistically significant (r=-0.58, p<0.001). The measurements conducted on the Turkish version of the Seizure Self-Efficacy Scale for Children showed that it is consistent with the original scale, valid and reliable for Turkish society.


The effect of an individual versus group program on weight loss.
The therapy of obesity is difficult and success rates are low. Because of these observations many different therapeutic modalities have been advocated. In this study the short term weight loss results using individual and group approaches are described. For both approaches changes in lifestyle and behaviours were emphasised. The major finding of the study was that while patient retention rates were better in the group approach, weight loss was greater in those patients who were seen individually. The reasons for these findings are discussed and some suggestions are made as to how the group approach, which has the significant advantage of making more efficient use of health professionals' time, might be made more therapeutically effective.


Stability of Pattern Formation in Systems with Dynamic Source Regions.
We explain the principles of gene expression pattern stabilization in systems of interacting, diffusible morphogens, with dynamically established source regions. Using a reaction-diffusion model with a step-function production term, we identify the phase transition between low-precision indeterminate patterning and the phase in which a traveling, well-defined contact zone between two domains is formed. Our model analytically explains single- and two-gene domain dynamics and provides pattern stability conditions for all possible two-gene regulatory network motifs.


Intralesional Bleomycin Injection for Propranolol-Resistant Hemangiomas.
Propranolol has been the first-line treatment for alarming hemangiomas. However, some hemangiomas are propranolol-resistant. The authors reported 1 propranolol-resistant hemangioma which was treated with intralesional bleomycin injections. Sixteen months after 3 injections, the lesion still remained stable. Its potential mechanism was clarified by ultrasonic monitoring. Intralesional bleomycin injection can be considered an ideal option in treating propranolol-resistant hemangiomas.


Arterial and tissue gas tensions in rats during development of pulmonary oxygen poisoning.
Oxygen and carbon dioxide tensions of arterial blood and subcutaneous tissue were studied in rats during 84 h of continuous exposure to oxygen. O2 and CO2 tensions in the subcutaneous tissue were measured by means of an implanted Silastic tonometer. As pulmonary edema developed after 48 h of exposure to oxygen, Pao2 started to decline and PaCO2 rose. Tissue Po2 decreased below the normal level already after 24 h of exposure, probably due to O2-induced vasoconstriction. After 84 h of oxygen exposure, the mean tissue Po2 was 29 mm Hg. In general, a distinctly hypoxic tissue microclimate was not observed. After 48 h of exposure to oxygen, the tissue PCO2 exceeded the control level. An 84-h exposure resulted in a profound retention of CO2, both in peripheral tissues and arterial blood. It is concluded that, in contrast to earlier suggestions, hypercapnia rather than hypoxia is the final factor leading to death in oxygen toxicity.


[Immigrant children in a pediatric department: what social problems?].
Hospital Fernando Fonseca is located in a suburban area that houses a great number of immigrants from developing countries. To characterize and compare the immigrant and portuguese pediatric populations which have been admitted and referred to Social Service department. Prospective study, from November 2004 to March 2005; demographic and socioeconomic data, diagnosis and social problems were analysed. A total of 35 children were observed, 22 (62.8%) immigrants, 42.9% of them less than 12-months old, with a predominance of female (54.5%), African origin (81.8%) and poor social-economical status (72.3%). The majority of parents (72.7%) came from a Portuguese Speaking African Country and 58.3% were illegal in our country. Most had a family doctor assigned (81.3%). Nineteen (87.5%) were admitted for organic disease and the social problem was detected later: poverty (9), negligence (7), physical aggression (3), abandon (2), psychological abuse (1), sexual abuse (1). Children were referred to Child Protection Committee (5) and Court (1); 6 children received economical support and 5 needed social support. When compared to the Portuguese population, social problems are more frequent in immigrant children (20% vs.7.5%; p =0,001), especially in African origin (81.8% vs.15.4%; p=0,00); low economic status (7.3% vs.55.6%; p =0.,423 ), poverty (37.5% vs. 26.6%; p=0.313) and physical aggression (13% vs. 8.3%; p =0.313) were more frequent in the immigrant and negligence being the most frequent social problem in the Portuguese population (33.3% vs. 29%; p =0.313). The growing number of immigrants and their social deficiencies raises important questions related to health care and social support for these families, to facilitate their social integration.


Habitat preference differentiates the Holocene range dynamics but not barrier effects on two sympatric, congeneric trees (Tristaniopsis, Myrtaceae).
Niche partitioning can lead to differences in the range dynamics of plant species through its impacts on habitat availability, dispersal, or selection for traits that affect colonization and persistence. We investigated whether niche partitioning into upland and riparian habitats differentiates the range dynamics of two closely related and sympatric eastern Australian trees: the mountain water gum (Tristaniopsis collina) and the water gum (T. laurina). Using genomic data from SNP genotyping of 480 samples, we assessed the impact of biogeographic barriers and tested for signals of range expansion. Circuit theory was used to model isolation-by-resistance across three palaeo-environment scenarios: the Last Glacial Maximum, the Holocene Climate Optimum and present-day (1950-2014). Both trees showed similar genetic structure across historically dry barriers, despite evidence of significant environmental niche differentiation and different post-glacial habitat shifts. Tristaniopsis collina exhibits the signature of serial founder effects consistent with recent or rapid range expansion, whilst T. laurina has genetic patterns consistent with long-term persistence in geographically isolated populations despite occupying a broader bioclimatic niche. We found the minor influence of isolation-by-resistance on both species, though other unknown factors appear to shape genetic variation. We postulate that specialized recruitment traits (adapted to flood-disturbance regimes) rather than habitat availability limited post-glacial range expansion in T. laurina. Our findings indicate that niche breadth does not always facilitate range expansion through colonization and migration across barriers, though it can promote long-term persistence in situ.


Effect of lamotrigine combined with felbamate on the horizontal (ambulatory) activity in mice.
Exploratory and spontaneous locomotor activities, after administration of some novel antiepileptic drugs (felbamate and lamotrigine alone or in combination), were evaluated in mice by means of the electronically monitored locomotor activity system (Digiscan analyzer). Felbamate (injected intraperitoneally, at the single dose of 25.7 mg/kg) significantly reduced behavioral activity in terms of horizontal (ambulatory) activity in mice. The combination of felbamate (25.7 mg/kg) with lamotrigine (2.3 mg/kg) drastically reduced this parameter during the first 15-min period (habituation to a novel environment--being the rate of exploratory locomotor activity) and the second 15-min interval (spontaneous locomotor activity). Moreover, neither the exploratory, nor spontaneous locomotor activity of the mice, were affected by lamotrigine (at the separate dose of 2.3 mg/kg) with respect to the ambulatory activity of the animals tested. Felbamate administered alone or combined with lamotrigine considerably impaired exploratory and spontaneous locomotor activities of the animals tested in terms of horizontal activity.


Altered low-frequency oscillation amplitude of resting state-fMRI in patients with discogenic low-back and leg pain.
The aim of this study was to explore the amplitude of intrinsic low-frequency oscillations (LFOs) in patients with discogenic low-back and leg pain (LBLP). We obtained and compared the LFO amplitude from 25 right-handed discogenic LBLP patients (13 males; mean age 55.16±1.83 years) and 27 well-matched healthy controls (15 males; mean age 52.96±1.63 years). The LFO amplitude was examined using the voxel-wise amplitude of low-frequency fluctuations (ALFFs), and partial correlation analysis was performed to determine the relationship between the regions with altered ALFF values and clinical parameters in discogenic LBLP patients. Compared with healthy controls, the patients with discogenic LBLP showed a significant increase in ALFF in the affective system of the pain matrix (left anterior cingulate cortex, right anterior insula/frontal operculum, and bilateral orbitofrontal cortex) and information-processing regions (middle occipital/temporal gyrus). In addition, a significant decrease in ALFF was observed in the default mode network (DMN; inferior parietal lobule (IPL) and medial prefrontal cortex [mPFC]) and the processing system of the pain matrix (basal ganglia/thalamus/midbrain, postcentral gyrus [PoCG], and fusiform gyrus). Several regions with altered ALFF were associated with disease duration, visual analog scale scores, Barthel index, and fine sensory modality measurements (two-point tactile discrimination of the left and/or right leg). Further operating characteristic curves analysis suggested that the mean ALFF values in the right IPL, left IPL/PoCG, left anterior cingulate cortex, and left mPFC could serve as markers to separate individuals with discogenic LBLP from healthy subjects. Our results revealed widespread abnormalities in ALFF in the pain matrix and information-processing regions as well as a decrease in ALFF in the DMN. These results open up an important new avenue to better understand the nature of the link between intrinsic activity and peripheral pain and sensory impairment in discogenic LBLP patients.


Learning from the messengers: innate sensing of viruses and cytokine regulation of immunity - clues for treatments and vaccines.
Virus infections are a major global public health concern, and only via substantial knowledge of virus pathogenesis and antiviral immune responses can we develop and improve medical treatments, and preventive and therapeutic vaccines. Innate immunity and the shaping of efficient early immune responses are essential for control of viral infections. In order to trigger an efficient antiviral defense, the host senses the invading microbe via pattern recognition receptors (PRRs), recognizing distinct conserved pathogen-associated molecular patterns (PAMPs). The innate sensing of the invading virus results in intracellular signal transduction and subsequent production of interferons (IFNs) and proinflammatory cytokines. Cytokines, including IFNs and chemokines, are vital molecules of antiviral defense regulating cell activation, differentiation of cells, and, not least, exerting direct antiviral effects. Cytokines shape and modulate the immune response and IFNs are principle antiviral mediators initiating antiviral response through induction of antiviral proteins. In the present review, I describe and discuss the current knowledge on early virus-host interactions, focusing on early recognition of virus infection and the resulting expression of type I and type III IFNs, proinflammatory cytokines, and intracellular antiviral mediators. In addition, the review elucidates how targeted stimulation of innate sensors, such as toll-like receptors (TLRs) and intracellular RNA and DNA sensors, may be used therapeutically. Moreover, I present and discuss data showing how current antimicrobial therapies, including antibiotics and antiviral medication, may interfere with, or improve, immune response.


Deficient Vitamin E Uptake During Development Impairs Neural Tube Closure in Mice Lacking Lipoprotein Receptor SR-BI.
SR-BI is the main receptor for high density lipoproteins (HDL) and mediates the bidirectional transport of lipids, such as cholesterol and vitamin E, between these particles and cells. During early development, SR-BI is expressed in extraembryonic tissue, specifically in trophoblast giant cells in the parietal yolk sac. We previously showed that approximately 50% of SR-BI-/- embryos fail to close the anterior neural tube and develop exencephaly, a perinatal lethal condition. Here, we evaluated the role of SR-BI in embryonic vitamin E uptake during murine neural tube closure. Our results showed that SR-BI-/- embryos had a very low vitamin E content in comparison to SR-BI+/+ embryos. Whereas SR-BI-/- embryos with closed neural tubes (nSR-BI-/-) had high levels of reactive oxygen species (ROS), intermediate ROS levels between SR-BI+/+ and nSR-BI-/- embryos were detected in SR-BI-/- with NTD (NTD SR-BI-/-). Reduced expression of Pax3, Alx1 and Alx3 genes was found in NTD SR-BI-/- embryos. Maternal α-tocopherol dietary supplementation prevented NTD almost completely (from 54% to 2%, p < 0.001) in SR-BI-/- embryos and normalized ROS and gene expression levels. In sum, our results suggest the involvement of SR-BI in the maternal provision of embryonic vitamin E to the mouse embryo during neural tube closure.


Effects of enzymatic degradation after loading in temporomandibular joint.
Synovial fluid of the joint decreases friction between the cartilage surfaces and reduces cartilage wear during articulation. Characteristic changes of synovial fluid have been shown in patients with osteoarthritis (OA) in the temporomandibular joint (TMJ). OA is generally considered to be induced by excessive mechanical stress. However, whether the changes in synovial fluid precede the mechanical overloading or vice versa remains unclear. In the present study, our purpose was to examine if the breakdown of joint lubrication affects the frictional properties of mandibular condylar cartilage and leads to subsequent degenerative changes in TMJ. We measured the frictional coefficient in porcine TMJ by a pendulum device after digestion with hyaluronidase (HAase) or trypsin. Gene expressions of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), type II collagen, and histology were examined after prolonged cyclic loading by an active pendulum system. The results showed that the frictional coefficient increased significantly after HAase (35%) or trypsin (74%) treatment. Gene expression of IL-1β, COX-2, and MMPs-1, -3, and -9 increased significantly in enzyme-treated TMJs after cyclic loading. The increase in the trypsin-treated group was greater than that in the HAase-treated group. Type II collagen expression was reduced in both enzyme-treated groups. Histology revealed surface fibrillation and increased MMP-1 in the trypsin-treated group, as well as increased IL-1β in both enzyme-treated groups after cyclic loading. The findings demonstrated that the compromised lubrication in TMJ is associated with altered frictional properties and surface wear of condylar cartilage, accompanied by release of pro-inflammatory and matrix degradation mediators under mechanical loading.


[FTIR spectroscopy studies on the apoptosis-promoting effect of TFAR19 on the erythroleukemia cell line MEL].
The changes in the cellular main components of the mouse erythroleukemia cell line MEL for TFAR19 gene transfection were studied by the technology of Fourier transform infrared spectroscopy (FTIR). Using the method of gene transfection with liposome, we obtained MEL-TF19 cell line, which stably carries TFAR19, a novel apoptosis-related gene. The expression of the gene on mRNA level was confirmed by RT-PCR. Then, FTIR spectra of the cells were measured in the course of apoptosis induced by serum deprivation. Our results indicated that after being transfected with TFAR19 gene, MEL-TF19 cells exhibited relatively higher protein content, higher transcriptional activity, and relatively lower phospholipid content as compared with those exhibited by MEL cells. All the above changes reflect the apoptosis-promoting effect of TFAR19 gene, and maybe account for the cellular rheological changes after TFAR19 gene transfection, which were discovered in our previous study.


Primary Ocular Adnexal Extranodal Marginal Zone Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma Presenting as Orbital Apex Syndrome.
A 75-year-old female with a past medical history significant for prior stroke and atrial fibrillation presented with acute onset of orbital apex syndrome with chemosis and periorbital ecchymosis. Following initial treatment to relieve intraocular pressure, she began spontaneously haemorrhaging retro-orbitally. Preliminary investigation with neuroimaging demonstrated a left orbital mass with extension into the orbital apex. A provisional diagnosis of cavernous haemangioma was made. She was treated with transorbital resection of the orbital mass. Subsequent histopathology revealed a diagnosis of ocular adnexal non-Hodgkin lymphoma of histologic type extranodal marginal zone of mucosa-associated lymphoid tissue (MALT lymphoma). MALT lymphoma should be considered in cases of orbital apex syndrome.


The effect of pertussis toxin on alpha 1-adrenoceptor-mediated vasoconstriction by the full agonist, cirazoline, and the partial agonist, (-)-dobutamine, in pithed rats.
The role of pertussis toxin-sensitive guanine nucleotide regulatory proteins (G-proteins) in the signal transduction process(es) involved in postjunctional vascular alpha 1-adrenoceptor-mediated vasoconstriction produced by the full agonist, cirazoline, and the partial agonist, (-)-dobutamine, have been investigated in the cardiovascular system of the pithed rat. Pertussis toxin pretreatment (50 micrograms/kg, iv, 3 days prior to experimentation) only slightly inhibited the pressor response of cirazoline, and the degree of inhibition produced by pertussis toxin was roughly equivalent to the inhibition produced by the calcium channel antagonist, nifedipine (1 mg/kg, ia). In contrast, pertussis toxin pretreatment produced marked inhibition of the alpha 1-adrenoceptor-mediated pressor response to the partial agonist, (-)-dobutamine, and this large degree of inhibition was qualitatively and quantitatively similar to the degree of inhibition produced by nifedipine. The differential pattern of inhibition of full and partial alpha 1-adrenoceptor agonists by pertussis toxin suggests that the vasoconstrictor response of an alpha 1-adrenoceptor partial agonist, which is more dependent upon the translocation of extracellular calcium than a full agonist, as evidenced by its sensitivity to inhibition by nifedipine, involves a pertussis toxin-sensitive G-protein that couples the alpha 1-adrenoceptor to the calcium channel. Furthermore, for alpha 1-adrenoceptor-mediated vasoconstriction by full agonists with high intrinsic efficacy, which involves both intracellular and extracellular pools of calcium, and particularly the former, pertussis toxin only inhibits that component of the alpha 1-adrenoceptor response which is dependent upon the translocation of extracellular calcium, accounting for the limited degree of inhibition of the response to cirazoline by pertussis toxin and by nifedipine. By inference, the other component of the alpha 1-adrenoceptor-mediated pressor response to a full agonist, which is dependent upon the mobilization of intracellular stores of calcium through a process believed to involve the activation of phospholipase C, likely utilizes a pertussis toxin insensitive G-protein that is distinct from that which we propose couples the alpha 1-adrenoceptor to the calcium channel. We conclude, therefore, that the alpha 1-adrenoceptor in the vasculature of the pithed rat may be coupled to 2 distinct G-proteins, only one of which is sensitive to inhibition by pertussis toxin and links the alpha 1-adrenoceptor to the membrane calcium channel, and which may be utilized by both full agonists and partial agonists.


Facial nerve neurilemmoma: report of four cases.
Four cases of facial nerve neurilemmoma are reported. Hearing loss was the initial symptom in all four of these patients, and among them, one had facial palsy before the operation. Physically, a bulging mass underneath the skin in the posteroinferior part of the ear canal was found in all of these patients. Excision of the tumor with nerve graft or hypoglossal-facial crossover was done in three of the patients. Postoperatively, they had fair facial nerve function with no tumor recurrence. The other case had excision only, and the tumor recurred after the operation.


Zfa is an expressed retroposon derived from an alternative transcript of the Zfx gene.
ZFY, a gene on the Y chromosome encoding a zinc finger protein, has been proposed as a candidate for the human testis determining gene. Sequences related to ZFY, called ZFX, are present on the X chromosome of a wide range of placental mammals. Unlike most mammals the mouse has four genes homologous to ZFY; two on the Y chromosome, Zfy-1 and Zfy-2, an X-linked gene, Zfx, and an autosomal gene, Zfa. We show here that Zfa has arisen recently by retroposition of one of at least three alternatively spliced mRNAs transcribed from the Zfx gene. Zfa is an unusual retroposon in that it has retained an open reading frame and is expressed, although its function may be limited or altered by the presence of a potentially inactivating mutation in the third of its zinc fingers. This mutation must have occurred at the same time or soon after the retroposition event as it is also present in the Zfa gene of Mus spretus. Interestingly the third finger of the M. musculus musculus Zfy-2 gene has also sustained a mutation suggesting that this gene family may be rapidly evolving in mice.


Microfabrication-Based Three-Dimensional (3-D) Extracellular Matrix Microenvironments for Cancer and Other Diseases.
Exploring the complicated development of tumors and metastases needs a deep understanding of the physical and biological interactions between cancer cells and their surrounding microenvironments. One of the major challenges is the ability to mimic the complex 3-D tissue microenvironment that particularly influences cell proliferation, migration, invasion, and apoptosis in relation to the extracellular matrix (ECM). Traditional cell culture is unable to create 3-D cell scaffolds resembling tissue complexity and functions, and, in the past, many efforts were made to realize the goal of obtaining cell clusters in hydrogels. However, the available methods still lack a precise control of cell external microenvironments. Recently, the rapid development of microfabrication techniques, such as 3-D printing, microfluidics, and photochemistry, has offered great advantages in reconstructing 3-D controllable cancer cell microenvironments in vitro. Consequently, various biofunctionalized hydrogels have become the ideal candidates to help the researchers acquire some new insights into various diseases. Our review will discuss some important studies and the latest progress regarding the above approaches for the production of 3-D ECM structures for cancer and other diseases. Especially, we will focus on new discoveries regarding the impact of the ECM on different aspects of cancer metastasis, e.g., collective invasion, enhanced intravasation by stress and aligned collagen fibers, angiogenesis regulation, as well as on drug screening.


Requiem for an eastern Pacific seagrass bed.
Few papers concerning seagrasses of the eastern Pacific have been published. This paper presents the first ecological data on the seagrass, Ruppia maritima, from a non-lagoonal setting in the eastern Pacific. A 5000 m2 patch formed by R. maritima, at Playa Iguanita, Bahía Culebra, Pacific coast of Costa Rica was studied. Plant density and leaf length of R. maritima were determined along two transects on different dates. Above and below ground biomass were calculated along one transect. Plant density ranged from 1590 to 8630 individuals m(-2) along the two transects, with means of 5990 +/- 1636 and 6100 +/- 1876 plants m(-2) for transect 1 and 2, respectively. Longest leaf length per plant varied between 0.5 and 23.0 cm. Leaf biomass (LB) ranged from 10 to 97 gm(-2), and root-rhizome biomass (RB) from 31 to 411 gm(-2), resulting in RB:LB ratios of 3.07 to 15.27. Total biomass at Bahía Culebra was lower than at tropical lagoons on the Pacific coast of Mexico, but higher than in the Gulf of Mexico. The below ground: above ground biomass ratio was much higher at Bahía Culebra than at other sites on the Pacific coast of Mexico and the Gulf of Mexico. Another seagrass present at Bahía Culebra was Halophila baillonii, with low densities on the deepest section of the patch. At least 44 invertebrate species associated with the seagrass bed have also been identified. The patch at Playa Iguanita and other sites within Bahía Culebra, as well as their associated organisms, disappeared after a severe storm in June 1996. No seagrasses have been found in the area or in any other location on the Pacific coast of Costa Rica since then.


[Non-chondromatous hamartoma].
A 69-year-old female visited our hospital because of dyspnea. Chest X-ray showed an abnormal shadow in the right lower lung field. Chest computed tomography (CT) showed a round, well-circumscribed, homogenous subpleural nodle of 8 mm in diameter in the right lower lobe, which had no calcification and no pleural indentation. Bronchofiber scope, abdominal CT, brain magnetic resonance imaging (MRI), bone scintigraphy could not establish definitive diagnosis. Scince the possibility of malignancy could not be excluded throughout, video-assisted thoracoscopic surgery was performed to obtain confirmed diagnosis. Pathological examination revealed non-chondromatous hamartoma of the lung. Non-chondromatous hamartoma should be considered in the differential diagnosis of pulmonary nodles. We report a rare case of non-chondromatous hamartoma.


Direct observation of completely processed calcium carbonate dust particles.
This study presents, for the first time, field evidence of complete, irreversible processing of solid calcium carbonate (calcite)-containing particles and quantitative formation of liquid calcium nitrate particles apparently as a result of heterogeneous reaction of calcium carbonate-containing mineral dust particles with gaseous nitric acid. Formation of nitrates from individual calcite and sea salt particles was followed as a function of time in aerosol samples collected at Shoresh, Israel. Morphology and compositional changes of individual particles were observed using conventional scanning electron microscopy with energy dispersive analysis of X-rays (SEM/EDX) and computer controlled SEM/EDX. Environmental scanning electron microscopy (ESEM) was utilized to determine and demonstrate the hygroscopic behavior of calcium nitrate particles found in some of the samples. Calcium nitrate particles are exceptionally hygroscopic and deliquesce even at very low relative humidity (RH) of 9-11% which is lower than typical atmospheric environments. Transformation of non-hygroscopic dry mineral dust particles into hygroscopic wet aerosol may have substantial impacts on light scattering properties, the ability to modify clouds and heterogeneous chemistry.


Is Pseudotumor Cerebri An Unusual Expression of Chiari Syndrome? A Case Report and Review of the Literature.
The Chiari I malformation (CM-I) is a developmental alteration of the posterior cranial fossa (PCF), radiographically defined as the descent of the cerebellar tonsils ≤ 5 mm below the foramen magnum (FM) inside the cervical canal. Headache is the most frequent symptom associated with CM-I. The association of CM-I and neurological symptoms configures with Chiari syndrome. A rare symptom associated with Chiari syndrome is intracranial hypertension syndrome with cephalea and papilloedema-the typical findings of pseudotumor cerebri (PTC). PTC is a syndrome characterized by signs and symptoms of increased intracranial pressure (ICP) in the absence of space-occupying masses and/or obstruction of the ventricular system detectable by neuroimaging. The most common symptoms are headache and visual disturbances. Literature reports that the association between CM-I and PTC has a prevalence of 2-6%. More recently, a prevalence of 11% has been described in a specific subset of obese or overweight female patients between 20 and 40 years old. Here we report the case of a 38-year-old woman who came to our observation with a clinical picture and neuroradiological examinations compatible with both CM-I and PTC. We discuss the clinical case and the significant improvement after surgical occipito-cervical decompression.


Novel compound heterozygous mutations in DYNC2H1 in a patient with severe short-rib polydactyly syndrome type III phenotype.
Short-rib polydactyly syndrome type III is an autosomal recessive lethal skeletal ciliopathy, which is phenotypically similar to nonlethal asphyxiating thoracic dystrophy. Mutations in DYNC2H1 have been identified in both of these disorders, indicating that they are variants of a single disorder. However, short-rib polydactyly syndrome type III is the more severe variant. Here, we report novel compound heterozygous mutations in DYNC2H1 (p.E1894fsX10 and p.R3004C) in a patient with typical short-rib polydactyly syndrome type III phenotype. R3004 is located within the microtubule-binding domain of DYNC2H1, and its substitution is predicted to disrupt the interaction with microtubules. Considering the severe phenotype of our patient, our findings suggest that R3004 may be a key residue for the microtubule-binding affinity of dynein.


Huanglian-Jie-Du-Tang Extract Ameliorates Depression-Like Behaviors through BDNF-TrkB-CREB Pathway in Rats with Chronic Unpredictable Stress.
Neuroinflammation is considered as one of the common pathogeneses of depression. Huanglian-Jie-Du-Tang (HJDT) is a traditional Chinese herbal formula. The present study investigates the antidepressant-like effect of HJDT and its possible mechanism in rats. Rats were given HJDT (2, 4, and 8 g/kg, intragastrically), paroxetine (1.8 mg/kg, intragastrically), or an equivalent volume of saline for 42 days. The depression-related behaviors, including sucrose preference test (SPT), open field test (OFT), novel objective recognition task (NORT), and forced swimming test (FST), were detected. 5-Hydroxytryptamine (5-HT) and dopamine (DA) contents, microglial activation, proinflammatory cytokines, and brain derived neurotrophic factor (BDNF), tropomyosin receptor kinases B (TrkB), and cAMP-responsive element binding protein (CREB) expression were investigated. The results indicated HJDT (2 and 4 g/kg) dramatically ameliorated the depression-like behaviors. Also HJDT decreased the number of microglia and the proinflammatory cytokines in hippocampus. Western-blotting analysis displayed HJDT upregulated BDNF, TrkB, and pCREB/CREB expression in hippocampus. Particularly, pCREB DNA activity enhanced with HJDT treatment in hippocampus. But there was no difference in the 5-HT and DA contents with HJDT treatment. In conclusion, it was supposed that HJDT might be a potential Chinese medicine decoction for treating or alleviating complex symptoms of depression through BDNF-TrkB-CREB pathway.


T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions.
Several key advances in the treatment of B-cell non-Hodgkin lymphoma (B-NHL) over the past two decades have strategically exploited B-cell lineage markers suitable for targeting by immunotherapies. First, the addition of the anti-CD20 monoclonal antibody (mAb) rituximab to a range of standard therapies conferred remarkable outcomes improvements in diverse settings, perhaps most prominently an overall survival advantage in newly diagnosed diffuse large B-cell lymphoma (DLBCL). Subsequently, multiple chimeric antigen receptor (CAR) T-cell therapies targeting CD19 have revolutionized the treatment of relapsed/refractory (rel/ref) DLBCL and are active in other B-NHL subtypes as well. Most recently, the longstanding aspiration to exploit patients' endogenous T-cells to combat lymphoma has been achieved via T-cell redirecting therapies such as bispecific antibodies (BsAbs) that incorporate dual targeting of a T-cell antigen such as CD3 plus a B-cell antigen such as CD19 or CD20 expressed by the tumor. These novel agents have demonstrated impressive activity as monotherapies in patients with heavily pre-treated, rel/ref B-NHL of a variety of subtypes. Now, myriad clinical trials are exploring combinations of T-cell redirectors with targeted therapies, antibody-drug conjugates, conventional chemotherapy, and even new immunotherapies. Here, we highlight key landmarks in the development of T-cell redirecting therapies for the treatment of B-NHL, emerging evidence and lessons from recent clinical trials, and exciting new directions in this arena.


Relationship between quinolone use and resistance of Staphylococcus epidermidis in patients with acne vulgaris.
Staphylococcus epidermidis is a bacterium known to inhabit the skin. In treatment of acne vulgaris, the cutaneous milieu is exposed to oral or topical antimicrobials. We previously reported that the antimicrobial resistance of Cutibacterium acnes isolated from acne patients is affected by antimicrobial use. The aim of this study was to investigate the relationship between quinolone use and resistance in skin bacteria, particularly S. epidermidis, from acne patients. A total of 92 and 87 S. epidermidis strains isolated from clinic patients and hospital outpatients with acne vulgaris, respectively, were tested. No significant difference was found between the prevalence of methicillin-resistant S. epidermidis (MRSE) strains from clinic patients (37.0%) and hospital outpatients (39.1%). The MRSE strains (20.6%, 14/68 strains) showed a significantly higher ratio of high-level levofloxacin resistance (minimum inhibitory concentrations were 64 to ≥256 μg/mL) compared with methicillin-susceptible S. epidermidis strains (2.7%, 3/111 strains) (P < 0.01). The rate of levofloxacin resistance in C. acnes strains, which were isolated from the same samples of acne patients, showed a strong positive correlation with that in S. epidermidis strains (r = 0.93, P < 0.01). The high-level levofloxacin-resistant strains were frequently found in patients with history of quinolone use compared with those without (P < 0.01). Our data showed for the first time that antimicrobial administration for acne treatment affects the antimicrobial resistance in not only C. acnes but also S. epidermidis. Thus, caution should be exercised in antimicrobial use for acne treatment to prevent increasing antimicrobial resistance in these species.


Detection of growth hormone and growth hormone-releasing hormone-related messenger RNA in rat leukocytes by the polymerase chain reaction.
To validate that growth hormone (GH) and growth hormone-releasing hormone (GHRH) can be produced by leukocytes, we have assessed the presence of GH and GHRH-related mRNA in leukocyte cultures by reverse transcription and the polymerase chain reaction. A sample of the polymerase chain reactions were size-fractionated by electrophoresis in a 0.8% agarose gel and examined with ultraviolet light after ethidium bromide staining. Single major DNA bands corresponding in length to the distance between the 5' ends of the two GH and GHRH specific primers, 603 base pairs and 260 base pairs, respectively, were obtained. The DNA bands hybridized specifically to GH- and GHRH-specific probes after Southern transfer to nitrocellulose. The identity of the GH polymerase chain reaction material was confirmed by restriction enzyme analysis. The results showed that GH and GHRH gene expression occurs in mononuclear leukocytes and support the idea that these neuroendocrine hormones may be common signal molecules between the immune and neuroendocrine systems.