An Automatic Learning-Based Framework for Robust Nucleus Segmentation.
Computer-aided image analysis of histopathology specimens could potentially provide support for early detection and improved characterization of diseases such as brain tumor, pancreatic neuroendocrine tumor (NET), and breast cancer. Automated nucleus segmentation is a prerequisite for various quantitative analyses including automatic morphological feature computation. However, it remains to be a challenging problem due to the complex nature of histopathology images. In this paper, we propose a learning-based framework for robust and automatic nucleus segmentation with shape preservation. Given a nucleus image, it begins with a deep convolutional neural network (CNN) model to generate a probability map, on which an iterative region merging approach is performed for shape initializations. Next, a novel segmentation algorithm is exploited to separate individual nuclei combining a robust selection-based sparse shape model and a local repulsive deformable model. One of the significant benefits of the proposed framework is that it is applicable to different staining histopathology images. Due to the feature learning characteristic of the deep CNN and the high level shape prior modeling, the proposed method is general enough to perform well across multiple scenarios. We have tested the proposed algorithm on three large-scale pathology image datasets using a range of different tissue and stain preparations, and the comparative experiments with recent state of the arts demonstrate the superior performance of the proposed approach.


Theoretical model and experimental study of red blood cell (RBC) deformation in microchannels.
The motion and deformation of red blood cells (RBCs) flowing in a microchannel were studied using a theoretical model and a novel automated rheoscope. The theoretical model was developed to predict the cells deformation under shear as a function of the cells geometry and mechanical properties. Fluid dynamics and membrane mechanics are incorporated, calculating the traction and deformation in an iterative manner. The model was utilized to evaluate the effect of different biophysical parameters, such as: inner cell viscosity, membrane shear modulus and surface to volume ratio on deformation measurements. The experimental system enables the measurement of individual RBCs velocity and their deformation at defined planes within the microchannel. Good agreement was observed between the simulation results, the rheoscope measurements and published ektacytometry results. The theoretical model results imply that such deformability measuring techniques are weakly influenced by changes in the inner viscosity of the cell or the ambient fluid viscosity. However, these measurements are highly sensitive to RBC shear modulus. The shear modulus, estimated by the model and the rheoscope measurements, falls between the values obtained by micropipette aspiration and laser trapping. The study demonstrates the integration of a theoretical model with a microfabricated device in order to achieve a better understanding of RBC mechanics and their measurement using microfluidic shear assays. The system and the model have the potential of serving as quantitative clinical tools for diagnosing deformability disorders in RBCs.


Combinatorial approaches to understanding polytypism in III-V nanowires.
Polytypism in III-V semiconductor nanowires is a topic that has received considerable attention in recent years. Achieving a pure nanowire crystal phase requires well-controlled and advanced parameter tuning for most III-V materials. Additionally, the new and unusual phases sometimes observed may present unique material properties if they can be controllably fabricated. With the prospect of using nanowires in applications within several different fields (including electronics, photonics, and life science), theoretical models are necessary to explain experimental trends and to attain a high level of crystal phase control. At present, there is no theoretical model (or combination of models) that fully explains how and why nanowire crystal structures commonly include several different polytypes. Here we use combinatorics and interlayer interactions to include higher order polytypes (4H and 6H) with the aim to explain nanowire crystal structure beyond the well-investigated zinc blende-wurtzite polytypism. Predictions from our theoretical models compare well with experimental results.


Activation of the rostromedial prefrontal cortex during the experience of positive emotion in the context of esthetic experience. An fNIRS study.
The contemplation of visual art requires attention to be directed to external stimulus properties and internally generated thoughts. It has been proposed that the medial rostral prefrontal cortex (rPFC; BA10) plays a role in the maintenance of attention on external stimuli whereas the lateral area of the rPFC is associated with the preservation of attention on internal cognitions. An alternative hypothesis associates activation of medial rPFC with internal cognitions related to the self during emotion regulation. The aim of the current study was to differentiate activation within rPFC using functional near infrared spectroscopy (fNIRS) during the viewing of visual art selected to induce positive and negative valence, which were viewed under two conditions: (1) emotional introspection and (2) external object identification. Thirty participants (15 female) were recruited. Sixteen pre-rated images that represented either positive or negative valence were selected from an existing database of visual art. In one condition, participants were directed to engage in emotional introspection during picture viewing. The second condition involved a spot-the-difference task where participants compared two almost identical images, a viewing strategy that directed attention to external properties of the stimuli. The analysis revealed a significant increase of oxygenated blood in the medial rPFC during viewing of positive images compared to negative images. This finding suggests that the rPFC is involved during positive evaluations of visual art that may be related to judgment of pleasantness or attraction. The fNIRS data revealed no significant main effect between the two viewing conditions, which seemed to indicate that the emotional impact of the stimuli remained unaffected by the two viewing conditions.


JEPEG: a summary statistics based tool for gene-level joint testing of functional variants.
Gene expression is influenced by variants commonly known as expression quantitative trait loci (eQTL). On the basis of this fact, researchers proposed to use eQTL/functional information univariately for prioritizing single nucleotide polymorphisms (SNPs) signals from genome-wide association studies (GWAS). However, most genes are influenced by multiple eQTLs which, thus, jointly affect any downstream phenotype. Therefore, when compared with the univariate prioritization approach, a joint modeling of eQTL action on phenotypes has the potential to substantially increase signal detection power. Nonetheless, a joint eQTL analysis is impeded by (i) not measuring all eQTLs in a gene and/or (ii) lack of access to individual genotypes. We propose joint effect on phenotype of eQTL/functional SNPs associated with a gene (JEPEG), a novel software tool which uses only GWAS summary statistics to (i) impute the summary statistics at unmeasured eQTLs and (ii) test for the joint effect of all measured and imputed eQTLs in a gene. We illustrate the behavior/performance of the developed tool by analysing the GWAS meta-analysis summary statistics from the Psychiatric Genomics Consortium Stage 1 and the Genetic Consortium for Anorexia Nervosa. Applied analyses results suggest that JEPEG complements commonly used univariate GWAS tools by: (i) increasing signal detection power via uncovering (a) novel genes or (b) known associated genes in smaller cohorts and (ii) assisting in fine-mapping of challenging regions, e.g. major histocompatibility complex for schizophrenia. JEPEG, its associated database of eQTL SNPs and usage examples are publicly available at http://code.google.com/p/jepeg/. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


Rifampin preventive therapy for tuberculosis infection: experience with 157 adolescents.
For persons infected with Mycobacterium tuberculosis resistant to isoniazid (INH), rifampin is recommended for the prevention of active disease. However, the adverse effects and acceptability of this preventive therapy are largely uncharacterized. We prospectively followed 157 high-school students exposed to, and probably infected with, M. tuberculosis strains resistant to INH. All 157 students were prescribed preventive therapy with rifampin (10 mg/kg up to 600 mg daily) for 24 wk. While receiving therapy, 41 (26%) reported one or more adverse effects; of these, 18 had therapy interrupted temporarily, two permanently. Four (2.5%) had alanine aminotransferase elevations greater than two times the upper limit of normal (range, 91 to 161 U/L); of these, one had therapy permanently stopped. Six (3.8%) self-discontinued therapy. No student was found to have active disease during the 2 yr of the study (exact 95% upper confidence limit, 2.2). We assumed that without preventive therapy, seven cases of tuberculosis would have occurred during these 2 yr. Therefore, we estimated that rifampin had a minimum protective effect of 56%. In conclusion, preventive therapy with rifampin was well tolerated and well accepted, and it appears effective in preventing active tuberculosis.


In vitro activity of chlorogenic acid against Aspergillus fumigatus biofilm and gliotoxin production.
Aspergillus (A.) fumigatus, one of the most common causes of life-threatening fungal infections in immunocompromised patients, shows resistance to antifungal agents as has a high propensity to forming a biofilm. The present study aimed to investigate the effects of chlorogenic acid (CRA) on A. fumigatus biofilm formation and integrity. Confocal laser scanning microscopy was performed to determine the inhibitory effects of CRA against A. fumigatus biofilm formation. Transmission electron microscopy was performed to investigate the ultrastructural changes of A. fumigatus biofilm after CRA exposure. High-performance liquid chromatography and reverse-transcription quantitative PCR were performed to determine the expression of gliotoxin production in biofilm culture. The results showed that CRA at sub-minimum inhibitory concentrations inhibited A. fumigatus biofilm formation. In addition, CRA could decreased the gliotoxin production in the biofilm culture supernatant through inhibiting the expression of master genes involved in gliotoxin biosynthesis. The present study provided useful information for the development of novel strategies to reduce the incidence of A. fumigatus biofilm-associated diseases.


Comparison of 68Ga-FAPI and 18F-FDG PET/CT in a Patient With Cholangiocellular Carcinoma: A Case Report.
The present study compared Ga-FAPI and F-FDG PET/CT in a patient with cholangiocellular carcinoma. In this case, Ga-FAPI PET shows much higher tumor-to-background contrast of primary tumor and reveals more metastatic lesions, especially the micrometastases of bones, than F-FDG PET.


Mitochondrial creatine kinase in human health and disease.
Mitochondrial creatine kinase (MtCK), together with cytosolic creatine kinase isoenzymes and the highly diffusible CK reaction product, phosphocreatine, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. Mitochondrial proteolipid complexes containing MtCK form microcompartments that are involved in channeling energy in form of phosphocreatine rather than ATP into the cytosol. Under situations of compromised cellular energy state, which are often linked to ischemia, oxidative stress and calcium overload, two characteristics of mitochondrial creatine kinase are particularly relevant: its exquisite susceptibility to oxidative modifications and the compensatory up-regulation of its gene expression, in some cases leading to accumulation of crystalline MtCK inclusion bodies in mitochondria that are the clinical hallmarks for mitochondrial cytopathies. Both of these events may either impair or reinforce, respectively, the functions of mitochondrial MtCK complexes in cellular energy supply and protection of mitochondria form the so-called permeability transition leading to apoptosis or necrosis.


Intentional communication: computationally easy or difficult?
Human intentional communication is marked by its flexibility and context sensitivity. Hypothesized brain mechanisms can provide convincing and complete explanations of the human capacity for intentional communication only insofar as they can match the computational power required for displaying that capacity. It is thus of importance for cognitive neuroscience to know how computationally complex intentional communication actually is. Though the subject of considerable debate, the computational complexity of communication remains so far unknown. In this paper we defend the position that the computational complexity of communication is not a constant, as some views of communication seem to hold, but rather a function of situational factors. We present a methodology for studying and characterizing the computational complexity of communication under different situational constraints. We illustrate our methodology for a model of the problems solved by receivers and senders during a communicative exchange. This approach opens the way to a principled identification of putative model parameters that control cognitive processes supporting intentional communication.


Bisphenol A Induces Histopathological, Hematobiochemical Alterations, Oxidative Stress, and Genotoxicity in Common Carp (Cyprinus carpio L.).
Bisphenol A (BPA) is one of the environmental endocrine disrupting toxicants and is widely used in the industry involving plastics, polycarbonate, and epoxy resins. This study was designed to investigate the toxicological effects of BPA on hematology, serum biochemistry, and histopathology of different organs of common carp (Cyprinus carpio). A total of 60 fish were procured and haphazardly divided into four groups. Each experimental group contained 15 fish. The fish retained in group A was kept as the untreated control group. Three levels of BPA 3.0, 4.5, and 6 mg/L were given to groups B, C, and D for 30 days. Result indicated significant reduction in hemoglobin (Hb), lymphocytes, packed cell volume (PCV), red blood cells (RBC), and monocytes in a dose-dependent manner as compared to the control group. However, significantly higher values of leucocytes and neutrophils were observed in the treated groups (P < 0.05). Results on serum biochemistry revealed that the quantity of glucose, cholesterol, triglycerides, urea, and creatinine levels was significantly high (P < 0.05). Our study results showed significantly (P < 0.05) increase level of oxidative stress parameters like reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) and lower values of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) in treated groups (4.5 mg/L and 6 mg/L)) in the brain, liver, gills, and kidneys. Our study depicted significant changes in erythrocytes (pear shaped erythrocytes, leptocytes, microcytes, spherocytes, erythrocytes with broken, lobed, micronucleus, blabbed, vacuolated nucleus, and nuclear remnants) among treated groups (4.5 mg/L and 6 mg/L). Comet assay showed increased genotoxicity in different tissues including the brain, liver, gills, and kidneys in the treated fish group. Based on the results of our experiment, it can be concluded that the BPA exposure to aquatic environment is responsible for deterioration of fish health, performance leading to dysfunction of multiple vital organs.


Stress analysis of different post-luting systems: a three-dimensional finite element analysis.
The longevity of endodontically treated teeth is usually determined by the adequacy of root canal treatments, coronal seal and favourable stress distribution within the remaining tooth tissues. The aim of this study was to investigate the influence of post material and luting cement on the biomechanics of endodontically treated teeth using three-dimensional finite element analysis (3-D FEA). A 3 mm section of endodontically treated canine tooth was scanned and reconstructed for 3-D modelling and FE analyses. A metal post (MP) and a glass fibre post (GFP) were tested individually with four luting cements [zinc phosphate (ZPH), glass ionomer (GI), resin modified glass ionomer (RMGI) and resin based cements (RC)]. A push-out test was conducted by subjecting all models to 100 N perpendicular loading at the post. The maximum stresses generated along the MP-cement interface were significantly higher than corresponding stresses in the GFP-cement interface regardless of the cement type. GFP generated seven times higher stresses within the root dentine than metal posts when ZPH and GI were used, and three times higher when RMGI and RC were used. The displacement of GFP was double (50 μ) the displacement of MP (20 μ) in all groups. The low elastic modulus of GFP generated lower stresses along its interface and higher stresses within the root dentine, therefore the probability of debonding and root fracture in the GFP group was lower.


Optical-fiber-integrated high-speed organic phototransistor with broadband imaging capacity.
Fiber optic communication is becoming the central pillar of modern high-speed communication technology, which involves the abundant fiber components. Currently, most of photodetectors are fabricated on the silicon chip, so mass fiber-to-chip interfaces increase the complexity of advanced optoelectronic system, and also grow the risk of optical information loss. Here, we report an all-fiber organic phototransistor by employing rubrene single crystal and few-layer graphene to realize the "plug-to-play" operation. The device shows a broadband photoresponse from the ultraviolet to visible range, with fast response times of approximately 130/170 µs and reasonable specific detectivity of 6 × 109 Jones, which is close to the level of commercial on-chip device. Finally, several imaging applications are successfully demonstrated by deploying this all-fiber device. Our work provided an efficient strategy for fabricating all-fiber organic devices, and confirmed their significant potential in future optical fiber optoelectronics.


Tunable color of Ce3+/Tb3+/Mn(2+)-coactivated CaScAlSiO6 via energy transfer: a single-component red/white-emitting phosphor.
A series of single-component red/white-emitting CaScAlSiO6:Ce(3+),Tb(3+),Mn(2+) phosphors have been synthesized by a solid-state reaction. It is observed that CaScAlSiO6:Ce(3+),Tb(3+) phosphors exhibit two dominating bands situated at 380 and 542 nm, originating from the allowed 5d → 4f transition of the Ce(3+) ion and the (5)D4 → (7)F(J) = (J = 6, 5, 4, 3) transition of the Tb(3+) ion, respectively. As for CaScAlSiO6:Ce(3+),Mn(2+), our results indicate that Mn(2+) may occupy not only a Ca(2+) site to generate an orange emission [Mn(2+)(I)] at 590 nm but also a Sc(3+) site to generate a red emission [Mn(2+)(II)] at 670 nm. Both energy transfers from Ce(3+) to Tb(3+) and from Ce(3+) to Mn(2+) in the CaScAlSiO6 host are investigated and have been demonstrated to be of the resonant type via a dipole-dipole mechanism. By proper tuning of the relative composition of Tb(3+)/Mn(2+), white light can also be achieved upon excitation of UV light, indicating that the developed phosphor may potentially be used as a single-component red/white-emitting phosphor for UV-light-emitting diodes.


Temperature influence on phases of the tension response to sudden reduction of muscle length.
Phasic tension transients following a quick release in muscle length were studied to obtain information about the mechanism of force generation at different temperatures. The isometric tetanic tension increased (Q10 = 1.5) in the temperature range of 1.4 degrees C to 11.4 degrees C. The instantaneous stiffness (tension drop during the applied quick release in relation to the percentage of change of length) is slightly reduced by increasing temperature (Q10 = 0.9). The rate constant of the early tension recovery (phase 2) increased with increasing temperature (Q10 = 1.8). The results indicate that the increase of tetanic tension with increasing temperature is due to an increasing amount of force, generated by each cross bridge and a higher speed of rotation of the myosin head. The number of force generating cross bridges defined by the instantaneous elasticity is nearly independent of temperature range studied.


Perceptions and decision-making with regard to pregnancy among HIV positive women in rural Maputo Province, Mozambique - a qualitative study.
In preventing the transfer of HIV to their children, the Ministry of Health in Mozambique recommends all couples follow medical advice prior to a pregnancy. However, little is known about how such women experience pregnancy, nor the values they adhere to when making childbearing decisions. This qualitative study explores perceptions and decision-making processes regarding pregnancy among HIV positive women in rural Maputo Province. In-depth interviews and five focus group discussions with fifty-nine women who had recently become mothers were carried out. In addition, six semi-structured interviews were held with maternity and child health nurses. The ethnographic methods employed here were guided by Bourdieu's practice theory. The study indicated that women often perceived pregnancy as a test of fertility and identity. It was not only viewed as a rite of passage from childhood to womanhood, but also as a duty for married women to have children. Most women did not follow recommended medical advice prior to gestation. This was primarily due to perceptions that decision-making about pregnancy was regarded as a private issue not requiring consultation with a healthcare provider. Additionally, stigmatisation of women living with HIV, lack of knowledge about the need to consult a healthcare provider prior to pregnancy, and unintended pregnancy due to inadequate use of contraceptive were crucial factors. Women's experiences and decisions regarding pregnancy are more influenced by social and cultural norms than medical advice. Therefore, education concerning sexual and reproductive health in relation to HIV/AIDS and childbearing is recommended. In particular, we recommend maternal and child healthcare nurses need to be sensitive to women's perceptions and the cultural context of maternity when providing information about sexual and reproductive health.


Persistent coccydynia--the importance of a differential diagnosis.
The authors present the case of a sacral chordoma in which the diagnosis was delayed as the patient was diagnosed and treated as coccydynia. Persistent, severe coccydynia following minor trauma is common but the symptom can also be caused by significant underlying disease. The correct diagnosis was made in this patient but after significant delay. The presentation of this case involved multiple specialties and provides several learning points regarding the importance of thorough history taking and clinical examination. It highlights the importance of 'red flag' symptoms of low back pain which need to be fully investigated.


Molecular basis for maintenance of fidelity during the CCA-adding reaction by a CCA-adding enzyme.
CCA-adding enzyme builds the 3'-end CCA of tRNA without a nucleic acid template. The mechanism for the maintenance of fidelity during the CCA-adding reaction remains elusive. Here, we present almost a dozen complex structures of the class I CCA-adding enzyme and tRNA mini-helices (mini-D(73)N(74), mini-D(73)N(74)C(75) and mini-D(73)C(74)N(75); D(73) is a discriminator nucleotide and N is either A, G, or U). The mini-D(73)N(74) complexes adopt catalytically inactive open forms, and CTP shifts the enzymes to the active closed forms and allows N(74) to flip for CMP incorporation. In contrast, unlike the catalytically active closed form of the mini-D(73)C(74)C(75) complex, the mini-D(73)N(74)C(75) and mini-D(73)C(74)N(75) complexes adopt inactive open forms. Only the mini-D(73)C(74)U(75) accepts AMP to a similar extent as mini-D(73)C(74)C(75), and ATP shifts the enzyme to a closed, active form and allows U(75) to flip for AMP incorporation. These findings suggest that the 3'-region of RNA is proofread, after two nucleotide additions, in the closed, active form of the complex at the AMP incorporation stage. This proofreading is a prerequisite for the maintenance of fidelity for complete CCA synthesis.


Evaluation of Onchocerciasis Transmission in Tanzania: Preliminary Rapid Field Results in the Tukuyu Focus, 2015.
To compare diagnostic tests for onchocerciasis in a setting that has suppressed transmission, a randomized, age-stratified study was implemented in an area in Tanzania that had received 15 rounds of annual mass drug administration (MDA) with ivermectin. Study participants (N = 948) from 11 villages underwent a questionnaire, skin examination, skin snips, and blood draw. The burden of symptomatic disease was low. Ov-16 antibody rapid diagnostic test (RDT) results were positive in 38 (5.5%) participants, with 1 (0.5%), 1 (0.4%), and 2 (0.8%) in children aged 0-5, 6-10, and 11-15 years, respectively. Despite significant impact of MDA on transmission, the area would have failed to meet World Health Organization serologic criteria for stopping MDA if a full evaluation had been conducted. The specificity of the RDT, which is 97-98%, may result in the identification of a number of false positives that would exceed the current stop MDA threshold.


Monte Carlo study for designing a dedicated "D"-shaped collimator used in the external beam radiotherapy of retinoblastoma patients.
Retinoblastoma is the most common intraocular malignancy in the early childhood. Patients treated with external beam radiotherapy respond very well to the treatment. However, owing to the genotype of children suffering hereditary retinoblastoma, the risk of secondary radio-induced malignancies is high. The University Hospital of Essen has successfully treated these patients on a daily basis during nearly 30 years using a dedicated "D"-shaped collimator. The use of this collimator that delivers a highly conformed small radiation field, gives very good results in the control of the primary tumor as well as in preserving visual function, while it avoids the devastating side effects of deformation of midface bones. The purpose of the present paper is to propose a modified version of the "D"-shaped collimator that reduces even further the irradiation field with the scope to reduce as well the risk of radio-induced secondary malignancies. Concurrently, the new dedicated "D"-shaped collimator must be easier to build and at the same time produces dose distributions that only differ on the field size with respect to the dose distributions obtained by the current collimator in use. The scope of the former requirement is to facilitate the employment of the authors' irradiation technique both at the authors' and at other hospitals. The fulfillment of the latter allows the authors to continue using the clinical experience gained in more than 30 years. The Monte Carlo code PENELOPE was used to study the effect that the different structural elements of the dedicated "D"-shaped collimator have on the absorbed dose distribution. To perform this study, the radiation transport through a Varian Clinac 2100 C/D operating at 6 MV was simulated in order to tally phase-space files which were then used as radiation sources to simulate the considered collimators and the subsequent dose distributions. With the knowledge gained in that study, a new, simpler, "D"-shaped collimator is proposed. The proposed collimator delivers a dose distribution which is 2.4 cm wide along the inferior-superior direction of the eyeball. This width is 0.3 cm narrower than that of the dose distribution obtained with the collimator currently in clinical use. The other relevant characteristics of the dose distribution obtained with the new collimator, namely, depth doses at clinically relevant positions, penumbrae width, and shape of the lateral profiles, are statistically compatible with the results obtained for the collimator currently in use. The smaller field size delivered by the proposed collimator still fully covers the planning target volume with at least 95% of the maximum dose at a depth of 2 cm and provides a safety margin of 0.2 cm, so ensuring an adequate treatment while reducing the irradiated volume.


Variants deficient in phagocytosis of latex beads isolated from the murine macrophagelike cell line J774.
Variants that lack the ability to ingest latex beads were isolated from the mouse macrophagelike cell line J774. Carboxylated latex beads were derivatized with polylysine and then daunomycin by a carbodiimide method. Cells that ingested such beads were killed; variants that survived were isolated. Variants were detected at very low frequency and only after nitrosoguanidine mutagenesis. Of 11 independent isolates, 10 showed a lowered rate of uptake of polystyrene beads (without daunomycin). All of these proved normal in rate and extent of Fc-mediated phagocytosis. There was essentially no change in sensitivity to free daunomycin in the variants compared to the parent. These results support the previous hypothesis that there are differences in the metabolic routes of receptor-mediated and nonspecific phagocytosis.


Congenital Hypofibrinogenemia; An Unexpected Culprit Of Blindness In An Infant.
Congenital hypofibrinogenemia is a rare haematological disorder in which the production of functional fibrinogen is impaired because of the inherited mutation. Hypofibrinogenemia affects the coagulation cascade leading to bleeding diathesis and one of its manifestations can be recurrent Vitreous haemorrhages, sometimes leading to irreversible loss of vision. Therefore, Hypofibrinogenemia must be included in the differential diagnosis of Vitreous haemorrhage, particularly in young children. We report a case of a four months old female infant who was brought by her mother to the unit since she was afraid that the child might be unable to see since she was not following things for the last one month. Her ophthalmologic examination revealed bilateral vitreous haemorrhages. Further workup for the cause of the bleeding confirmed the diagnosis of hypofibrinogenemia which was then managed accordingly.


Feeling the beat: a smart hand exoskeleton for learning to play musical instruments.
Individuals who have suffered neurotrauma like a stroke or brachial plexus injury often experience reduced limb functionality. Soft robotic exoskeletons have been successful in assisting rehabilitative treatment and improving activities of daily life but restoring dexterity for tasks such as playing musical instruments has proven challenging. This research presents a soft robotic hand exoskeleton coupled with machine learning algorithms to aid in relearning how to play the piano by 'feeling' the difference between correct and incorrect versions of the same song. The exoskeleton features piezoresistive sensor arrays with 16 taxels integrated into each fingertip. The hand exoskeleton was created as a single unit, with polyvinyl acid (PVA) used as a stent and later dissolved to construct the internal pressure chambers for the five individually actuated digits. Ten variations of a song were produced, one that was correct and nine containing rhythmic errors. To classify these song variations, Random Forest (RF), K-Nearest Neighbor (KNN), and Artificial Neural Network (ANN) algorithms were trained with data from the 80 taxels combined from the tactile sensors in the fingertips. Feeling the differences between correct and incorrect versions of the song was done with the exoskeleton independently and while the exoskeleton was worn by a person. Results demonstrated that the ANN algorithm had the highest classification accuracy of 97.13% ± 2.00% with the human subject and 94.60% ± 1.26% without. These findings highlight the potential of the smart exoskeleton to aid disabled individuals in relearning dexterous tasks like playing musical instruments.


Hepatic ammonia metabolism in a uricotelic treefrog Phyllomedusa sauvagei.
Glutamine synthetase, a mitochondrial enzyme in liver of uricotelic reptiles and birds, is present in the cytosolic compartment of Phyllomedusa sauvagei liver. The average level is sufficient to account for the rate of uric acid excretion by adult frogs but is far lower than that present in birds and reptiles. Except for lower carbamoylphosphate synthetase activity, the activities of the urea cycle enzymes in P. sauvagei liver are comparable with those in adult ureotelic amphibians. The subcellular distribution of the urea cycle enzymes is much the same as in ureotelic amphibians and mammals with the possible exception of the occurrence of a small percentage of the carbamoylphosphate synthetase and ornithine transacarbamylase activities in the cytosol. In keeping with the subcellular localization of the enzymes, citrulline, and not glutamine, is formed by isolated liver mitochondria. The rapid degradation of glutamine by these mitochondria suggests a high degree of compartmentation of glutamine in the cytosol of P. sauvagei if it is to function as a precursor of uric acid in this compartment.


Synthesis of Conjugated Polymers Containing B←N Bonds with Strong Electron Affinity and Extended Absorption.
The B←N is isoelectronic to the C-C, with the former having stronger dipole moment and higher electron affinity. Replacing the C-C bonds in conjugated polymers with B←N bonds is an effective pathway toward novel polymers with strong electron affinity and adjustable optoelectronic properties. In this work, we synthesize a conjugated copolymer, namely, BNIDT-DPP, based on a B←N embedded unit, BNIDT, and a typical electron-deficient unit, diketopyrrolopyrrole (DPP). For comparison, the C-C counterpart, i.e., IDT-DPP, is also synthesized. In contrast to IDT-DPP, the B←N embedded polymer BNIDT-DPP shows an extended absorption edge (836 versus 978 nm), narrowed optical bandgap (1.48 versus 1.27 eV), and higher electron affinity (3.54 versus 3.74 eV). The Gaussian simulations reveal that the B←N embedded polymer BNIDT-DPP is more electron-deficient in contrast to IDT-DPP, supporting the decreased bandgap and energy levels of BNIDT-DPP. Organic thin-film transistor (OTFT) tests indicate a well-defined p-type characteristic for both IDT-DPP and BNIDT-DPP. The hole mobilities of IDT-DPP and BNIDT-DPP tested by OTFTs are 0.059 and 0.035 cm2/V·s, respectively. The preliminary fabrication of all-polymer solar cells based on BNIDT-DPP and PBDB-T affords a PCE of 0.12%. This work develops a novel B←N embedded polymer with strong electron affinity and extended absorption, which is potentially useful for electronic device application.


Identification of six novel allosteric effectors of Arabidopsis thaliana aspartate kinase-homoserine dehydrogenase isoforms. Physiological context sets the specificity.
The Arabidopsis genome contains two genes predicted to code for bifunctional aspartate kinase-homoserine dehydrogenase enzymes (isoforms I and II). These two activities catalyze the first and the third steps toward the synthesis of the essential amino acids threonine, isoleucine, and methionine. We first characterized the kinetic and regulatory properties of the recombinant enzymes, showing that they mainly differ with respect to the inhibition of the homoserine dehydrogenase activity by threonine. A systematic search for other allosteric effectors allowed us to identify an additional inhibitor (leucine) and 5 activators (alanine, cysteine, isoleucine, serine, and valine) equally efficient on aspartate kinase I activity (4-fold activation). The six effectors of aspartate kinase I were all activators of aspartate kinase II activity (13-fold activation) and displayed a similar specificity for the enzyme. No synergy between different effectors could be observed. The activation, which resulted from a decrease in the Km values for the substrates, was detected using low substrates concentrations. Amino acid quantification revealed that alanine and threonine were much more abundant than the other effectors in Arabidopsis leaf chloroplasts. In vitro kinetics in the presence of physiological concentrations of the seven allosteric effectors confirmed that aspartate kinase I and II activities were highly sensitive to changes in alanine and threonine concentrations. Thus, physiological context rather than enzyme structure sets the specificity of the allosteric control. Stimulation by alanine may play the role of a feed forward activation of the aspartate-derived amino acid pathway in plant.


Comparative post-harvest behaviour of traditional and virus-resistant Muchamiel tomatoes.
Nowadays, organoleptic quality is the primary objective for almost all tomato breeding programmes. In this study, post-harvest behaviour of a breeding line with genetic resistance to important viruses (tomato mosaic virus, tomato spotted wilt virus and tomato yellow leaf curl virus) has been compared with the original traditional landrace (Muchamiel). The breeding line has been obtained by backcrossing, introgressing three resistance genes but aiming to keep the quality characteristics of the traditional variety. Tomatoes were picked at random and stored at 10 degrees C for 13 days. Quality analyses were made in both tomato samples: weight loss, colour, respiration rate, ethylene production, maturity index, instrumental hardness and sensory evaluation with trained panel. Fruits of the breeding line were characterized by higher hardness even with a higher maturity index. Results of sensory tests were in agreement with instrumental measurements. Organoleptic quality of Muchamiel virus-resistant tomatoes was at least as high as that of traditional tomatoes, reaching the best scores in odour and aroma at the 13th storage day. Although a long time has been required to develop the breeding line, results indicate that organoleptic fruit quality has been recovered through backcrossing, confirming the success of the breeding programme.


Parental influences on pathogen resistance in brown trout embryos and effects of outcrossing within a river network.
Phenotypic plasticity can increase tolerance to heterogeneous environments but the elevations and slopes of reaction norms are often population specific. Disruption of locally adapted reaction norms through outcrossing can lower individual viability. Here, we sampled five genetically distinct populations of brown trout (Salmo trutta) from within a river network, crossed them in a full-factorial design, and challenged the embryos with the opportunistic pathogen Pseudomonas fluorescens. By virtue of our design, we were able to disentangle effects of genetic crossing distance from sire and dam effects on early life-history traits. While pathogen infection did not increase mortality, it was associated with delayed hatching of smaller larvae with reduced yolk sac reserves. We found no evidence of a relationship between genetic distance (W, FST) and the expression of early-life history traits. Moreover, hybrids did not differ in phenotypic means or reaction norms in comparison to offspring from within-population crosses. Heritable variation in early life-history traits was found to remain stable across the control and pathogen environments. Our findings show that outcrossing within a rather narrow geographical scale can have neutral effects on F1 hybrid viability at the embryonic stage, i.e. at a stage when environmental and genetic effects on phenotypes are usually large.


Lipooligosaccharide Structure is an Important Determinant in the Resistance of Neisseria Gonorrhoeae to Antimicrobial Agents of Innate Host Defense.
The strict human pathogen Neisseria gonorrhoeae has caused the sexually transmitted infection termed gonorrhea for thousands of years. Over the millennia, the gonococcus has likely evolved mechanisms to evade host defense systems that operate on the genital mucosal surfaces in both males and females. Past research has shown that the presence or modification of certain cell envelope structures can significantly impact levels of gonococcal susceptibility to host-derived antimicrobial compounds that bathe genital mucosal surfaces and participate in innate host defense against invading pathogens. In order to facilitate the identification of gonococcal genes that are important in determining levels of bacterial susceptibility to mediators of innate host defense, we used the Himar I mariner in vitro mutagenesis system to construct a transposon insertion library in strain F62. As proof of principle that this strategy would be suitable for this purpose, we screened the library for mutants expressing decreased susceptibility to the bacteriolytic action of normal human serum (NHS). We found that a transposon insertion in the lgtD gene, which encodes an N-acetylgalactosamine transferase involved in the extension of the α-chain of lipooligosaccharide (LOS), could confer decreased susceptibility of strain F62 to complement-mediated killing by NHS. By complementation and chemical analyses, we demonstrated both linkage of the transposon insertion to the NHS-resistance phenotype and chemical changes in LOS structure that resulted from loss of LgtD production. Further truncation of the LOS α-chain or loss of phosphoethanolamine (PEA) from the lipid A region of LOS also impacted levels of NHS-resistance. PEA decoration of lipid A also increased gonococcal resistance to the model cationic antimicrobial polymyxin B. Taken together, we conclude that the Himar I mariner in vitro mutagenesis procedure can facilitate studies on structures involved in gonococcal pathogenesis.


Solvent water tapes in two hydrates of mu-oxo-bis[bis(2,2'-bipyridine-kappa2N,N')(sulfato-kappaO)iron(III)].
The title compound, [Fe2O(SO4)2(C10H8N2)4], crystallizes as two different hydrates, viz. 11H2O, (I), and 15H2O, (II). The complex is binuclear, in which the two FeIII atoms are coordinated in an octahedral geometry to four N atoms from the two bipyridine ligands, to one O atom from the sulfate ion and to an oxide ion on a twofold axis, which acts as a bridge between the symmetry-related units. The Fe...Fe separation is 3.556 (4) A and the Fe-O-Fe angle is 161.6 (2) degrees in (I); the corresponding values are 3.544 (1) A and 165.8 (2) degrees in (II). In (II), one of the O atoms of the sulfate ion is disordered over two positions. In both compounds, the solvent water molecules form slightly different one-dimensional hydrogen-bonded networks which pass along the c axis of the unit cell. In (I), three solvent water molecules and, in (II), one solvent water molecule, are situated on the twofold axis. In both (I) and (II), the central O atom of the metal complex lies on a twofold axis.


Association between reduced pulmonary diffusing capacity and cardiac autonomic dysfunction in Type 1 diabetes.
In Type 1 diabetes mellitus (DM), it has been suggested that autonomic nervous system dysfunction (NAD) impairs lung diffusion capacity. Heart rate variability (HRV), a measure of cardiac autonomic function, is a sensitive method of detecting NAD. To our knowledge, no previous study has assessed whether cardiac sympatho-vagal balance is associated with lung diffusion capacity in diabetes. Twenty Type 1 DM patients without pulmonary abnormalities and systemic NAD underwent measurement of lung diffusion capacity for carbon monoxide (DLCO) by single-breath method and assessment of cardiac autonomic function by HRV analysis on 24-h electrocardiographic Holter recordings. Standard respiratory function tests and peripheral autonomic tests were normal in all patients. DLCO was lower than normal reference values in six patients (30%). DLCO correlated significantly with most HRV variables, independent of the clinical and laboratory variables. The strongest correlation was found with standard deviation of all RR intervals (SDNN; r = 0.62, P = 0.003) in the time domain and low frequency (LF) power (r = 0.73, P < 0.001) in the frequency domain. In Type 1 diabetes, a significant association exists between cardiac NAD and reduced DLCO in the absence of clinical respiratory and autonomic abnormalities. Thus, NAD may be involved in the early reduction of DLCO in these patients, possibly through abnormalities in the regulation of pulmonary blood flow at the microvascular level.


Tubing length for long-term oxygen therapy.
Most patients on long-term oxygen therapy use stationary oxygen delivery systems. It is not uncommon for guidelines to instruct patients to use tubing lengths no longer than 19.68 ft (6 m) when using an oxygen concentrator and 49.21 ft (15 m) when using cylinders. However, these concepts are not based on sufficient evidence. Thus, our objective was to evaluate whether a 98.42-ft (30-m) tubing length affects oxygen flow and FIO2 delivery from 1 cylinder and 2 oxygen concentrators. The 3 oxygen delivery systems were randomly selected, and 1, 3, and 5 L/min flows and FIO2 were measured 5 times at each flow at the proximal and distal outlets of the tubing by a gas-flow analyzer. Paired Student t test was used to analyze the difference between flows and FIO2 at proximal and distal outlets of tubing length. A total of 45 flows were measured between proximal and distal outlets of the 98.42-ft (30-m) tubing. Flows were similar for 1 and 3 L/min, but distal flow was higher than proximal flow at 5 L/min (5.57×5.14 L/min, P<.001). FIO2 was lower at distal than proximal outlet tubing at flows 1, 3, and 5 L/min, but the mean difference between measurements was less than 1%. Tubing length of 98.42 ft (30 m) may be used by patients for home delivery oxygen with flows up to 5 L/min, as there were no important changes in flows or FIO2.


[Ebola and the global governance of health].
The high state of anxiety about Ebola virus and its possible spread in the Western world has seemingly changed the route of the disease, for which effective vaccines and medicines do not exist. The rapid spread of the virus provides a paradigmatic narrative about the failure of today's governance for health, grounded on a series of global initiatives focussed on pathologies prioritized by the donors' community, at the detriment of health promotion and the strengthening of health systems in countries. The Ebola crisis also delivers a powerful account about the consequences of the de-potentiation of the World Health Organization (WHO), once the leading organization in public health policy-making. Today, the WHO is increasingly weak technically, politically and financially. While the virus remains out of control, the WHO's capacity to play a role in accompanying the development of the new essential vaccines and in brokering the conditions for accessibility and availability of the new medical tools remains to be questioned.


Error probability performance of a short-reach multicore fiber optical interconnect transmission system.
A standalone module for rectangular array multicore fiber (MCF)-based optical interconnect (OI) is realized that includes inherent intercore crosstalk and provides space division multiplexed coupling/decoupling of optical power. The module is integrated in a short-reach communication system to provide bit error probability (BEP). Next, a closed-form equation for BEP applicable to MCF OI with intercore crosstalk is derived. For characteristic parameters of the module, results obtained by two approaches agree within 1% for 40 Gbps per channel and predict an error-free transmission of aggregated data rate of 2.5 Tbps through the MCF OI under consideration.


Polypharmacy and Potential Drug-Drug Interactions in Home-Dwelling Older People - A Cross-Sectional Study.
Risks associated with polypharmacy and drug-drug interactions represent a challenge in drug treatment, especially in older adults. The aim of the present study was to assess the use of prescription and non-prescription drugs and the frequency of potential drug-drug interactions in home-dwelling older individuals. A cross-sectional study design was applied. Data were collected during preventive home visits among individuals aged ≥75 in three separate communities of Western Norway. A questionnaire, which was filled out by the individual, their next-of-kin, and the nurse performing the home visit was used for the collection of demographic and clinical data (age, sex, medication use, diagnoses, need of assistance with drug administration). Potential drug-drug interactions were identified electronically by IBM Micromedex Drug Interaction Checking. Point prevalence of potential drug-drug interactions and polypharmacy (≥5 drugs) were calculated. Binary logistic regression analyses were performed to assess factors potentially associated with polypharmacy or potential drug-drug interactions. Among the 233 individuals (mean age 78±3 years, 46% male) included in the study, 43% used ≥5 drugs, 3.4% ≥10 drugs, while 4.3% used no drugs. In 54% of the 197 individuals using two or more drugs, at least one potential drug-drug interaction was detected. Low-dose aspirin and simvastatin were most frequently involved in potential drug-drug interactions. In total, 25% of the individuals reported current use of drugs sold over the counter of which more than 95% were analgesic drugs. Potential drug-drug interactions involving ibuprofen were identified in nine of 11 (82%) individuals using over-the-counter ibuprofen. The study revealed a high prevalence of polypharmacy and potential drug-drug interactions with both prescription and non-prescription drugs in older home-dwelling individuals. Close monitoring of the patients at risk of drug-drug interactions, and increased awareness of the potential of over-the-counter drugs to cause drug-drug interactions, is needed.


Use of costic acid, a natural extract from Dittrichia viscosa, for the control of Varroa destructor, a parasite of the European honey bee.
Costic acid has been isolated from the plant Dittrichia viscosa and its efficacy against Varroa destructor, a parasite of Apis mellifera, the European honey bee, has been studied. Costic acid exhibited potent in vivo acaricidal activity against the parasite. Initial experiments showed that the compound is not toxic for human umbilical vein endothelial cells (HUVEC) at concentrations of up to 230 micromolar (μM), indicating that costic acid could be used as a safe, low-cost and efficient agent for controlling varroosis in honey bee colonies.


Developmental expression of the muscle-specific isozyme of phosphoglycerate mutase in human muscle cultured in monolayer and innervated by fetal rat spinal cord.
The electrophoretic pattern of phosphoglycerate mutase of adult innervated normal human muscle is composed predominantly of the muscle-specific isozyme, whereas the electrophoretic pattern of aneurally cultured human muscle is composed only of the brain-specific isozyme. We studied the transition of the isozymes (phosphogluterate mutase) in human muscle cultured in monolayer and innervated for 20 to 83 days by rat embryo spinal cord explants. In this culture system, regions of innervated muscle fibers in close proximity to the ventral part of the spinal cord explant continuously contracted and the contractions were reversibly blocked by 1 mM d-tubocurarine. In those innervated cultured human muscle fibers, the total activity of phosphoglycerate mutase was increased and the muscle-specific isozyme was expressed. The amount of muscle-specific isozyme directly correlated with the duration of innervation. This study demonstrated that expression of the gene for the muscle-specific isozyme of phosphoglycerate mutase in human muscle cultured in monolayer is influenced by de novo innervation.


Favorable outcome of neonatal cerebrospinal fluid shunt-associated Candida meningitis with caspofungin.
Invasive Candida infections associated with medical devices are very difficult to cure without device removal. We present a case of neonatal cerebrospinal fluid shunt-associated Candida meningitis, in which removal of the device was precluded, that was successfully treated with caspofungin. Pharmacokinetic assessment of caspofungin concentrations in cerebrospinal fluid showed that exposure was adequate in the presence of a high systemic exposure. In complex cases of neonatal Candida infections involving medical devices, the addition of caspofungin might be beneficial.


Lateral femoral chondral lesions are more frequent when an anterior cruciate ligament tear is concomitant with a lateral femoral notch sign, but do not progress over time.
The lateral femoral notch sign (LFNS) is caused by an impact to the lateral femoral condyle during a pivot shift injury and affects 25% to 33% of patients with an anterior cruciate ligament (ACL) rupture. The primary aim of this study was to compare the incidence of chondral lesions 1 year after ACL reconstruction, while taking into consideration preoperative chondral damage, in patients with and without a preoperative LFNS. The primary outcome measure was the presence of chondral lesions involving the lateral femoral condyle, confirmed on magnetic resonance imaging (MRI) using the Outerbridge classification, at 1 year postoperative. The secondary outcome measures were bone bruise of the lateral femoral condyle confirmed on MRI, the international knee documentation committee (IKDC), Lysholm and Tegner functional scores taken 1 year after surgery. Sixty patients were included-30 with preoperative LFNS and 30 without-in a retrospective, comparative study of prospectively collected data on patients operated between August 2018 and December 2020. A lateral femoral chondral lesion 1 year after surgery was significantly more common in the group with a preoperative LFNS (37% (N=11) versus 13% (N=4) in the group without a preoperative LFNS, p= .036). Adjusting the statistical analysis for preoperative body mass index (BMI) did not impact these results (adjusted odds ratio (OR) =3.83 [95% CI: 1.03-14.24]; p=.045]. Adjusting for a preoperative lateral femoral chondral lesion had an impact on these results (adjusted OR=0.78 [95% CI:0.12-5.08]; p=.793). This indicates that a preoperative LFNS is not significantly and independently associated with a lateral femoral chondral lesion at 1 year postoperative when the analysis is adjusted for a preoperative lateral femoral chondral lesion. However, having a preoperative lateral femoral chondral lesion is significantly correlated with the presence of a lateral femoral chondral lesion 1 year after the surgery (adjusted OR =63.31 [95%CI: 5.94-674.8]; p=.001). There were no significant differences in terms of bone bruise on MRI (p=1.0), or for the IKDC (p=.310), Lysholm (p=.416) and Tegner (p=.644) functional scores. The LFNS was still present in 21 out of 30 patients (70%) at 1 year postoperative. The preoperative LFNS was significantly smaller in the group without a chondral lesion compared to the group with a chondral lesion 1 year after the surgery (median = 2.30 mm [IQR: 1.40; 3.00] versus 3.10 mm [IQR: 2.50; 3.40]; p value = .045). Patients with a preoperative LFNS are three times more likely to have a chondral lesion in the notch region 1 year after surgery. These chondral lesions are concomitant to the injury and do not progress over time. III.


Oxidation of leucine by Leishmania donovani.
The metabolism of leucine by Leishmania donovani was investigated. Washed promastigotes were incubated with [1-14C]- or [U-14C]leucine or [1-14C]alpha-ketoisocaproate (KIC) and 14CO2 release was measured. The amount of KIC-derived acetyl-CoA oxidized in the citric acid cycle was computed. Promastigotes from mid-stationary phase cultures oxidized each of these labeled substrates less rapidly than cells from late log phase cultures, and significantly less acetyl-CoA derived from KIC oxidation was oxidized in the citric acid cycle. Glucose was a stronger inhibitor than was acetate of CO2 formation in the citric acid cycle in log phase promastigotes, but the reverse was observed in cells from mid-stationary phase. Alanine also inhibited leucine catabolism, but glutamate had little effect. Acute hypo-osmotic stress did not affect leucine catabolism, but hyper-osmotic stress caused appreciable inhibition of leucine oxidation. Cells grown under hypo- or hyper-osmotic conditions showed no changes in the effects of hypo- or hyper-osmotic stress on leucine catabolism, i.e. L. donovani is not an osmoconformer with respect to leucine metabolism. Leucine utilization in L. donovani was insensitive to a number of drugs that affect leucine metabolism in mammalian cells, indicating that the leucine pathway in L. donovani is not regulated in the same manner as in mammalian cells.


Preeclampsia: From Inflammation to Immunoregulation.
Preeclampsia (PE) affects 5% to 7% of pregnant women each year worldwide, accounts for up to 18% of maternal deaths in the United States each year, and is the number 1 cause of premature births. Preeclampsia is associated with hypertension after the 20th week of gestation with or without proteinuria, in conjunction with fetal growth restriction, maternal endothelial dysfunction, and chronic immune activation. The mechanisms leading to the development of PE are unclear. However, it is thought that shallow trophoblast invasion and insufficient remodeling of uterine spiral arteries result in placental ischemia. Consequently, an immune imbalance characterized by increases in proinflammatory CD4+ T cells and cytokines along with decreases in regulatory T cells and anti-inflammatory cytokines occurs. This imbalance leads to chronic inflammation and ensuing oxidative stress, proinflammatory cytokines, and autoantibodies. Studies performed in our laboratories, using the Reduced Uterine Perfusion Pressure (RUPP) rat model of placental ischemia, have demonstrated a role for this immune imbalance to mediate PE pathophysiology and identified potential mechanisms of immunoregulation that may be of benefit in the treatment of PE. Therefore, the purpose of this commentary is to review studies demonstrating the positive effects of immunoregulatory factors in the RUPP rat model of PE. Restoration of the immune balance in PE may be a potential strategy for the development of therapeutic interventions that could improve maternal and fetal outcomes associated with this maternal syndrome.


Clinico- Radiological Profile and Outcome of Isolated Paramedian Hemipontine Infarcts.
To study the clinico- radiological profile and outcome of isolated paramedian hemipontine infarcts. This is a prospective cross- sectional study. 50 consecutive patients admitted between January 2019 and December 2020 with a diagnosis of isolated paramedian hemipontine stroke were included. The locations of the infarcts were classified as follows- caudal; middle; rostral; dorsomedian; caudal and middle; and middle and rostral pons. The clinico- radiological profiles were studied and the outcomes were assessed using NIHSS (National Institutes of Health Stroke Scale) and mRS (modified Rankin score). Data was analysed using SPSS 22 version software. Paired t-test was used as a test of significance to identify the mean differences between the two quantitative variables. Majority of the subjects were 51- 60 years (34 percent). The most common risk factors were hypertension and type 2 diabetes mellitus. The most common clinical features were hemiparesis and speech disturbances. Pure motor hemiparesis (PMH) is the common syndrome seen in paramedian hemipontine strokes with infarcts located in caudal; middle; caudal and middle; and middle and rostral pons. In ataxic hemiparesis, infarcts were located in dorsomedian pons. In dysarthria clumsy hand syndrome, infarcts were located at rostral pons. 44 percent of the subjects had left vertebral artery abnormality. There was a statistically significant difference in the mean NIHSS and mRS when compared at admission/ discharge and at 3 months. Isolated paramedian hemipontine stroke syndromes have good topographical correlation with patients usually having a good functional outcome at the end of three months.


Effect of Different sp2 Bond Contents on the Reactivity and Mechanical Properties of Coke Carbon: A ReaxFF Molecular Dynamics Study.
In this study, ReaxFF-MD was used to construct a large-molecule model of coke containing 3000 atoms, and the sp2 bond content of the model was controlled by changing the heating and cooling rates. The increase of the sp2 bond content led to a significant difference in the reactivity of coke. The presence of the sp2 bond caused the carbon atoms inside the coke to change into a circular structure, making it more difficult for the gaseous atoms to adsorb on the surface of the coke. It significantly reduced the gasification reaction rate of coke in the CO2 and H2O atmospheres. In the tensile simulation experiment, it was found that the stretching process of coke was mainly divided into three stages: an elastic stretching stage, a plastic stretching stage, and a model fracture stage. During the stretching process, the carbon ring structure would undergo a C-C bond fracture while generating carbon chains to resist stress. The results indicated that the presence of sp2 bonds can effectively reduce the phenomenon of excessive local stress on coke to improve its tensile resistance. The method developed in this paper may provide further ideas and platforms for the research on coke performance.


Clinicopathological and prognostic role of MMP-9 in esophageal squamous cell carcinoma: a meta-analysis.
Many studies reported that matrix metalloproteinase-9 (MMP-9) participated in the development of esophageal squamous cell carcinoma (ESCC) and resulted in poor prognosis, however, they all included few patients and had inconsistent results. So we conducted a meta-analysis to explore the correlation between overexpression of MMP-9 and the clinicopathological characteristics and overall survival (OS) of ESCC. PubMed, EMBASE, Web of Science, Chinese Biomedical Literature Database, Google Scholar and other databases were searched for relevant studies. The Newcastle-Ottawa quality assessment scale was used to assess the methodological quality of included study and RevMan 5.2 software was used to conduct meta-analysis. A total of 35 studies were included, and the results of meta-analysis showed that overexpression of MMP-9 was associated with grade of differentiation [well/moderate vs. poor: odds ratio (OR): 0.39, 95% confidence interval (CI): 0.29-0.52; P<0.00001], lymph node metastasis (negative vs. positive: OR: 0.24, 95% CI: 0.16-0.34; P<0.00001), TNM stage (T1/T2 vs. T3/T4: OR: 0.28, 95% CI: 0.14-0.54; P=0.0002), the depth of invasion (T1/T2 vs. T3/T4: OR: 0.29, 95% CI: 0.17-0.49; P<0.00001), and vascular invasion of ESCC (negative vs. positive: OR: 0.35, 95% CI: 0.21-0.58; P<0.0001), and also associated with poor overall survival of ESCC (HR: 2.17, 95% CI: 1.32-3.57; P=0.002). Subgroup analysis showed that more than 10% of carcinoma cell staining was associated with significant increase of mortality risk (HR: 2.44, 95% CI: 1.16-5.15; P=0.02), and sensitive analysis suggested that MMP-9 was an independent prognostic factor in ESCC (HR: 1.49, 95% CI: 1.16-1.91; P=0.002). On the basis of limited evidence, overexpression of MMP-9 may be a potential independent prognosis factor of ESCC patients in Asia, and high-quality studies assessing the prognostic significance of MMP-9 for ESCC patients are still needed.


LncRNA LOC653786 promotes growth of RCC cells via upregulating FOXM1.
Renal cell carcinoma (RCC) is the most common kidney malignancy with poor prognosis. Recently, long noncoding RNAs (lncRNAs) have been demonstrated as important regulators in multiple cancers including RCC. LOC653786 is a lncRNA, but its role in cancer remains unclear. In this study, we for the first time found that LOC653786 was upregulated in RCC tissues and cell lines, and this lncRNA promoted growth and cell cycle progression of RCC cells. Moreover, we showed that LOC653786 elevated the expression of forkhead box M1 (FOXM1) and its downstream target genes cyclin D1 and cyclin B1 in RCC cells. Reporter assay revealed that LOC653786 enhanced the transcriptional activity of FOXM1 gene promoter. Additionally, knockdown of FOXM1 attenuated the LOC653786-enhanced growth and cell cycle progression of RCC cells. Meanwhile, silencing of LOC653786 suppressed RCC cell growth and cell cycle progression, which was alleviated by overexpression of FOXM1. The in vivo experiments in nude mice showed knockdown of LOC653786 repressed xenograft tumor growth and FOXM1 expression. In conclusion, our results demonstrate that LOC653786 accelerates growth and cell cycle progression of RCC cells via upregulating FOXM1, suggesting that the 'LOC653786/FOXM1' pathway may serve as a novel target for RCC treatment.


Kinesin-5 mediated chromosome congression in insect spindles.
The microtubule motor protein kinesin-5 is well known to establish the bipolar spindle by outward sliding of antiparallel interpolar microtubules. In yeast, kinesin-5 also facilitates chromosome alignment "congression" at the spindle equator by preferentially depolymerizing long kinetochore microtubules (kMTs). The motor protein kinesin-8 has also been linked to chromosome congression. Therefore, we sought to determine whether kinesin-5 or kinesin-8 facilitates chromosome congression in insect spindles. RNAi of the kinesin-5 Klp61F and kinesin-8 Klp67A were performed separately in Drosophila melanogaster S2 cells to test for inhibited chromosome congression. Klp61F RNAi, Klp67A RNAi, and control metaphase mitotic spindles expressing fluorescent tubulin and fluorescent Cid were imaged, and their fluorescence distributions were compared. RNAi of Klp61F with a weak Klp61F knockdown resulted in longer kMTs and less congressed kinetochores compared to control over a range of conditions, consistent with kinesin-5 length-dependent depolymerase activity. RNAi of the kinesin-8 Klp67A revealed that kMTs relative to the spindle lengths were not longer compared to control, but rather that the spindles were longer, indicating that Klp67A acts preferentially as a length-dependent depolymerase on interpolar microtubules without significantly affecting kMT length and chromosome congression. This study demonstrates that in addition to establishing the bipolar spindle, kinesin-5 regulates kMT length to facilitate chromosome congression in insect spindles. It expands on previous yeast studies, and it expands the role of kinesin-5 to include kMT assembly regulation in eukaryotic mitosis.


Study of the efficacy and safety of switching from risperidone to paliperidone in elderly patients with schizophrenia.
We investigated the clinical efficacy and safety of switching to paliperidone (PAL) in elderly schizophrenia patients receiving risperidone. The subjects were 27 inpatients who had been diagnosed with schizophrenia according to the DSM-IV. The patient's clinical symptoms were assessed using the Positive and Negative Syndrome Scale and the Clinical Global Impression-Severity of Illness Scale, and their safety was assessed using the Drug-induced Extrapyramidal Symptoms Scale, bodyweight, body mass index, and laboratory tests. We also investigated patient satisfaction using the Drug Attitude Inventory, a subjective outcome measure. No significant differences in clinical symptom improvement efficacy were seen between the PAL-switching group and the control group. The mean changes from baseline on the Drug-induced Extrapyramidal Symptoms Scale total score, Drug Attitude Inventory score, and prolactin level were significantly greater in the PAL-switching group than in the control group. Furthermore, patients with PAL needed less biperiden, even though they had similar risperidone-equivalent daily dosages to the control group. The results of this study suggest that switching elderly patients from risperidone to PAL may result in superior safety and patient satisfaction, and may also make it possible to reduce the dosage of biperiden.


Structure and Piezoelectricity Due to B Site Cation Variation in ABn+Cln+2 Hybrid Histammonium Chlorometallate Materials.
To provide new insights for understanding the influence of B site cations on the structure in chlorometallate materials of the form ABn+Cln+2, we report novel organic-inorganic hybrid metallates (OIHMs) incorporating histammonium (HistNH3) dications and various transition-metal and main group B site cations. Single crystals of OIHMs with the basic formula (HistNH3Mn+Cln+2, M = Fe, Co, Ni, Cu, Zn, Cd, Hg, Sb, Sn, Pb, Bi) were grown and their structures characterized by single-crystal X-ray crystallography. HistNH3CoCl4, HistNH3ZnCl4, and HistNH3SbCl5 were crystallized in a non-centrosymmetric space group and were subsequently studied with piezoresponse force microscopy (PFM). While bulk measurements of crystals and poly(vinylidene difluoride) (PVDF)/metallate composite films exhibited low bulk response values, the surface-measured local response values using PFM were 5.17 pm/V for HistNH3CoCl4, 22.6 pm/V for HistNH3ZnCl4, and 2.9 pm/V for HistNH3SbCl5 compared with 2.50 pm/V for PVDF reference samples. The magnitudes of the d33 coefficient, net dipole, and cation-Cl bond dipole obtained from the density functional theory calculations confirm the higher response in HistNH3ZnCl4 compared to HistNH3CoCl4. Density of states and crystal orbital Hamilton population analysis indicate that the higher net dipole in HistNH3ZnCl4 compared to HistNH3CoCl4 is due to the lower hybridization of the M-Cl bond.


Thick melanoma in Tuscany.
The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type lifestyle, where there is a progressively increasing incidence and a low but not decreasing mortality - even increasing in selected cases, especially in the older age groups. Also in Tuscany there is a steady rise in the incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case-case study, thin and thick melanoma cases, trying to find out those personal and tumor characteristics which may help to customize preventive interventions. The study included nine centers involved in the melanoma diagnosis. A consecutive series of incident invasive melanomas diagnosed in a period of about 18 months (July 2010 to December 2011) was collected and matched according in a ratio of one thick melanoma (cutoff thickness: 1 mm) every two thin melanomas. The investigators filled in a questionnaire on patients' self-reported sun exposure, way of melanoma detection, awareness and performance of self-skin examination, as well as propensity to prevention in general. The results of this survey confirm that older age and the lower education level are associated with a later detection. The habit of performing skin self-examination is crucial in the early diagnosis of thick melanoma. The results of this survey seem to suggest that population aged over 50 years, with few total and few atypical nevi, and limited sun exposure and burning are at higher risk of late diagnosis. It can be assumed that part of the population is not effectively reached by prevention campaigns because they do not recognize themselves as being at risk for skin cancers. In order to achieve a higher rate of early diagnosis of skin melanoma, a new strategy must be implemented. It could be useful to rethink educational campaigns - which seem to unintentionally leave out subjects more at risk for melanoma - and to renew the active involvement of the general practitioners.


[Antitrypsin activity of the urine and alpha 1 protease inhibitor].
The urinary trypsin inhibitory capacity (TIC) is mainly due to the excretion of an inhibitor which is immunologically related to inter-alpha:trypsin inhibitor (ITI). However, alpha 1 protease inhibitor (alpha 1 PI) can be found in urine of patients with proteinuria. When this one is greater than 1 g/l, the measured TIC is more or less markedly related to the amount of alpha 1 PI present in the analyzed sample. The antitryptic activity of alpha 1 PI can be ruled out by incubating urine with specific anti-alpha 1 PI immunoglobulins. An identical result is obtained by acidification of the sample prior to TIC determination. Moreover, after freezing of urine, only the antitryptic activity of alpha 1 PI is strikingly decreased. Thus, in the presence of a significant proteinuria (greater than 1 g/l), a preliminary acidification of urine allows a suitable and specific measurement of TIC due to the inhibitor immunologically related to ITI. Thus, this one is a sensitive, useful and easy test for detecting and monitoring infections.


Safety evaluation of driver cognitive failures and driving errors on right-turn filtering movement at signalized road intersections based on Fuzzy Cellular Automata (FCA) model.
This paper proposes a simulation-based approach to estimate safety impact of driver cognitive failures and driving errors. Fuzzy Logic, which involves linguistic terms and uncertainty, is incorporated with Cellular Automata model to simulate decision-making process of right-turn filtering movement at signalized intersections. Simulation experiments are conducted to estimate the relationships between cognitive failures and driving errors with safety performance. Simulation results show Different types of cognitive failures are found to have varied relationship with driving errors and safety performance. For right-turn filtering movement, cognitive failures are more likely to result in driving errors with denser conflicting traffic stream. Moreover, different driving errors are found to have different safety impacts. The study serves to provide a novel approach to linguistically assess cognitions and replicate decision-making procedures of the individual driver. Compare to crash analysis, the proposed FCA model allows quantitative estimation of particular cognitive failures, and the impact of cognitions on driving errors and safety performance.


LPS-induced microglial secretion of TNFα increases activity-dependent neuronal apoptosis in the neonatal cerebral cortex.
During the pre- and neonatal period, the cerebral cortex reveals distinct patterns of spontaneous synchronized activity, which is critically involved in the formation of early networks and in the regulation of neuronal survival and programmed cell death (apoptosis). During this period, the cortex is also highly vulnerable to inflammation and in humans prenatal infection may have a profound impact on neurodevelopment causing long-term neurological deficits. Using in vitro and in vivo multi-electrode array recordings and quantification of caspase-3 (casp-3)-dependent apoptosis, we demonstrate that lipopolysaccharide-induced inflammation causes rapid alterations in the pattern of spontaneous burst activities, which subsequently leads to an increase in apoptosis. We show that these inflammatory effects are specifically initiated by the microglia-derived pro-inflammatory cytokine tumor necrosis factor α and the chemokine macrophage inflammatory protein 2. Our data demonstrate that inflammation-induced modifications in spontaneous network activities influence casp-3-dependent cell death in the developing cerebral cortex.


A phase II clinical trial of mefloquine in Brazilian male subjects.
Mefloquine was compared with sulfadoxine-pyrimethamine for safety and efficacy in a randomized, double-blind clinical trial in adult males from a malaria-endemic area of Brazil. A total of 99 oligosymptomatic and symptomatic volunteers with Plasmodium falciparum parasitaemia took part in the trial; 49 were given 1000 mg of mefloquine and the remainder received 1500 mg of sulfadoxine plus 75 mg of pyrimethamine, in a single oral dose.Mefloquine was 100% successful in clearing parasitaemia within 7 days; there were no recrudescences. Sulfadoxine-pyrimethamine was less successful; 35 cases showed an S-type response, 8 an RI response, 3 an RII, and 2 an RIII response. The side-effects of mefloquine were mild and transient and included headache, nausea, vomiting, dizziness, and diarrhoea. A satisfactory weight gain and rise in haemoglobin level were seen in both groups.


Prone position lateral interbody fusion-a narrative review.
Lateral access lumbar interbody fusion is an increasingly popular procedure that allows for anterior column support through discectomy, endplate preparation, and interbody insertion. This procedure was initially described and performed with the patient in the lateral decubitus position. This would typically be followed by repositioning the patient to the prone position for pedicle screw fixation. Increasingly common is the lateral access lumbar interbody fusion in the prone position. This narrative review seeks to summarize the available literature on advantages, disadvantages, and unique features of the prone position lateral access lumbar interbody fusion. We performed a narrative review of articles published up to 01 November 2022 through a PubMed search. The search terms "prone lateral spine surgery" and "lateral approach spine surgery" AND "prone position" were used. Articles not available in English were excluded. The search result abstracts were independently reviewed by 2 authors and 28 full text articles were reviewed. Both reviewing authors were orthopedic surgery chief residents. There are several unique advantages as well as disadvantages to the prone position lateral interbody fusion. Some advantages include ease of placing pedicle screws, simultaneous posterior and lateral access, greater ease in achieving segmental lumbar lordosis, and a relatively safer positioning of the psoas muscle, lumbar plexus, and abdominal structures. Disadvantages include more difficulties with exposure and retraction, as well as visualization, positioning and ergonomics of surgery. Prone position lateral interbody fusion is an increasingly prevalent and useful surgical technique with several advantages and disadvantages when compared to lateral interbody fusion in the lateral decubitus position. There are several surgical indications and goals for which prone lateral interbody fusion may provide significant benefit when compared to other interbody fusion techniques.


A review of mothers' prenatal and postnatal quality of life.
Contemporary broad descriptions of health and well-being are reflected in an increasing appreciation of quality of life issues; in turn this has led to a growing number of tools to measure this. This paper reviews articles cited in MEDLINE, CINAHL and BIDS which have addressed the concept of quality of life in pregnancy and the period following childbirth. It describes five groups of articles: those explicitly assessing quality of life in this area; those using broader health assessments as an indicator of quality of life; those articles equating quality of life with certain pregnancy outcomes in identified groups of patients; those studies which identify the possibility of pregnancy as an outcome measure and infer from this that quality of life has been improved; and those articles which are themselves reviews or commentaries of pregnancy and childbirth and which identify quality of life as a feature. The term 'quality of life' is used inconsistently in the literature. There are few quality of life tools specifically designed for the maternity care setting. Improved or adversely affected quality of life is frequently inferred from certain clinical conditions.


Nutrition transition in Morocco.
To analyse the nutritional transition in Morocco. Examination of Moroccan national survey data. Morocco is undergoing a demographic, epidemiological and social transition. The urban population increased from 29% in 1960 to 53% in 1997. Per capita gross domestic product increased steadily from 1972 to 1999. Life expectancy at birth increased to 70 years in 1999 from 47 years in 1962. Both infant and juvenile mortalities have decreased, from 92/1000 and 69/1000 in 1982-87 to 46/1000 and 37/1000 in 1992-97, respectively. In parallel, the diet changed considerably: the intake of animal products increased while that of cereals and sugar remained relatively high, reflecting the specificity of Moroccan dietary habits. The rise in the consumption of meats and vegetables was accompanied by a steady consumption of bread, used to eat the sauce in which the meat and vegetables are cooked. Sugar is mainly used in tea, the very sweet, national drink consumed throughout the day. Under-nourishment persists among children under five (23% stunting and 10% underweight in 1997) while overweight is rising (9% in 1997 compared with 3% in 1987 for children under three). Among adults, overweight (body mass index (BMI) > 25 kg m(-2)) increased from 26% in 1984 to 36% in 1998. It is higher among women (32% in 1984 and 45% in 1998) than among males (19% in 1984 and 25% in 1998). It is also higher among urban populations (30% in 1984 and 40% in 1998) than rural populations (20% in 1984 and 29% in 1998). Obesity (BMI > 30kg m(-2)) increased from 4% in 1984 to 10% in 1998. Overweight seems to be positively associated with economic status but negatively with education level. Overweight and obesity constitute major health problems in Morocco.


Surface-displayed antibodies as a tool for simultaneously controlling the arrangement and morphology of multiple cell types with microscale precision.
Cell-cell interactions are considered to play critical roles in the development and physiology of most tissues. However, it is not straightforward to analyze cell-cell interactions with conventional cell culture in which cells are randomly distributed. To overcome this limitation, we employed here an antibody display to sort different cell types onto separate regions on a single substrate with microscale precision, taking advantage of the specific recognition of cell surface markers by surface-displayed antibodies. The results obtained with two sets of cell combinations, T cell/myelomonocytoid cell and neuron/astrocyte, demonstrate that antibody displays are feasible to establish a site-addressable coculture.


Live longer on MARS: a yeast paradigm of mitochondrial adaptive ROS signaling in aging.
Adaptive responses to stress, including hormesis, have been implicated in longevity, but their mechanisms and outcomes are not fully understood. Here, I briefly summarize a longevity mechanism elucidated in the budding yeast chronological lifespan model by which Mitochondrial Adaptive ROS Signaling (MARS) promotes beneficial epigenetic and metabolic remodeling. The potential relevance of MARS to the human disease Ataxia-Telangiectasia and as a potential anti-aging target is discussed.


Trichosporon on humans: a practical account.
Six human pathogenic Trichosporon species are described with respect to criteria for routine identification, epidemiology and clinical origin: T. ovoides, T. inkin, T. asahii, T. asteroides (Fissuricella filamenta), T. cutaneum, and T. mucoides. These species are causative agents of white piedra and cutaneous infections and are involved in systemic, localized or disseminated mycoses, particularly in patients with underlying haematological malignancy. Data on in vitro sensitivity to antifungal drugs are provided.


Serum pancreatic secretory trypsin inhibitor (PSTI) level predicts early stage of pancreas allograft rejection.
Serum Pancreatic Secretory Trypsin Inhibitor (PSTI) as a marker of rejection was examined in the course of canine pancreatic transplantation. In the case of allotransplantation without immunosuppression, serum PSTI showed two significant elevations: The first elevation on the first day after transplantation was related to operative procedures and the second elevation on the sixth or seventh day reflected early stage of rejection, because the first elevation was observed after both autotransplantation and allotransplantation and biopsies of pancreas grafts showed nonspecific neutrophilic infiltration on the first day and typical interstitial lymphoid infiltrates with cellular rejection of the exocrine tissue on the seventh day. In contrast, in the case of allotransplantation with immunosuppression (cyclosporine and prednisolone), serum PSTI showed only the first elevation due to the operative procedures. Biopsies of the pancreas allografts showed nonspecific neutrophilic infiltration until the third day and no interstitial lymphoid infiltrates on the seventh day. In addition, when the salvage immunosuppression was started at the beginning of the second PSTI elevation (on the seventh day), serum PSTI level was clearly declined and there were survivals of the grafts to over two weeks in six of eight dogs. Biopsies of the pancreas grafts taken on the seventh day after starting the salvage immunosuppression showed almost normal pancreatic architecture except moderate fibrosis in the exocrine tissue. The results show that serum PSTI can detect early stage of pancreas graft rejection so that the salvage immunosuppression can be implemented effectively.


Quantitative and morphological analysis of dentate granule cells with recurrent basal dendrites from normal and epileptic rats.
Granule cells with recurrent basal dendrites (RBDs) were previously reported in both control and epileptic rats. RBDs are dendrites that arise from the basal half of granule cell bodies and curve toward and extend into the molecular layer. They are increased in frequency in the pilocarpine model of epilepsy. The present study was undertaken to analyze the distribution and morphology of granule cells with RBDs and the synaptic connections of RBDs. Granule cells were labeled by retrograde transport of biocytin. Those with an RBD were found throughout the granule cell layer, but were most numerous at the hilar border. The morphology of these cells varied in the different depths of the granule cell layer; the angle of their cell body's long axis was mainly vertical at the hilar margin, and changed to virtually horizontal close to the molecular layer border. Quantitative data on the distribution of granule cells with RBDs and the angle of the cell body's long axis confirmed these descriptions. At the electron microscopic level, RBDs showed the typical features of dendrites and formed numerous axodendritic and axospinous synapses with labeled and unlabeled axon terminals. These results showed that RBDs of granule cells from epileptic rats are postsynaptic to axon terminals, including mossy fibers, and thus are involved in a similar synaptic circuitry as apical dendrites of granule cells from these animals.


Shenmai Injection Protects Against Doxorubicin-Induced Cardiotoxicity via Maintaining Mitochondrial Homeostasis.
Shenmai injection (SMI), as a patented traditional Chinese medicine, is extracted from Panax ginseng and Ophiopogon japonicus. It commonly used in the treatment of cardiovascular disease and in the control of cardiac toxicity induced by doxorubicin (DOX) treatment. However, its anti-cardiotoxicity mechanism remains unknown. The purpose of this study was to investigate the underlying mitochondrial protective mechanisms of SMI on DOX-induced myocardial injury. The cardioprotective effect of SMI against DOX-induced myocardial damage was evaluated in C57BL/6 mice and H9c2 cardiomyocytes. In vivo, myocardial injury, apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB/Akt)/glycogen synthase kinase 3 beta (GSK-3β) signaling pathway related proteins were measured. In vitro, apoptosis, mitochondrial superoxide, mitochondrial membrane potential, mitochondrial morphology, levels of mitochondrial fission/fusion associated proteins, mitochondrial respiratory function, and AMP-activated protein kinase (AMPK) activity were assessed. To further elucidate the regulating effects of SMI on AMPK and PI3K/Akt/GSK-3β signaling pathway, compound C and LY294002 were utilized. In vivo, SMI decreased mortality rate, levels of creatine kinase, and creatine kinase-MB. SMI significantly prevented DOX-induced cardiac dysfunction and apoptosis, decreased levels of Bax/Bcl-2 and cleaved-Caspase3, increased levels of PI3K, p-Akt, and p-GSK-3β. In vitro, SMI rescued DOX-injured H9c2 cardiomyocytes from apoptosis, excessive mitochondrial reactive oxygen species production and descending mitochondrial membrane potential, which were markedly suppressed by LY294002. SMI increased ratio of L-OPA1 to S-OPA1, levels of AMPK phosphorylation, and DRP1 phosphorylation (Ser637) in order to prevent DOX-induced excessive mitochondrial fission and insufficient mitochondrial fusion. In conclusion, SMI prevents DOX-induced cardiotoxicity, inhibits mitochondrial oxidative stress and mitochondrial fragmentation through activation of AMPK and PI3K/Akt/GSK-3β signaling pathway.


The CobraPLA during anesthesia with controlled ventilation: a clinical trial of efficacy.
The CobraPLA (CPLA) is a relatively new supraglottic airway device that has not been sufficiently investigated. Here, we performed a prospective observational study to evaluate the efficacy of the CPLA during controlled ventilation. In 50 anesthetized and paralyzed patients undergoing elective surgery a CPLA was inserted and inflated to an intracuff pressure of 60 cm H2O. The success rate of insertion upon the first attempt was 82% (41/50), with a mean insertion time of 16.3 +/- 4.5 seconds. The adequacy of ventilation was assessed by observing the end tidal CO2 waveform, movement of the chest wall, peak airway pressure (13.5 cm H2O), and leak fraction (4%). We documented the airway sealing pressure (22.5 cm H2O) and noted that the the site of gas leaks at that pressure were either at the neck (52%), the abdomen (46%), or both (2%). In 44 (88%) patients, the vocal cords were visible in the fiberoptic view through the CPLA. There was no gastric insufflation during the anesthesia. Respiratory and hemodynamic parameters remained stable during CPLA insertion. Postoperative blood staining of CPLA was minimal, occurring in 22% (11/50) of patients. Mild and moderate throat soreness was reported in 44% (22/50) and 4% (2/50) of patients, respectively. Lastly, mild dysphonia was observed in 6% (3/50) of patients and mild dysphagia in 10% (5/50) of patients. Our results indicated that the CPLA is both easy to place and allows adequate ventilation during controlled ventilation.


The Christian physician in the non-Christian institution: objections of conscience and physician value neutrality.
Christian physicians are in danger of losing the right of conscientious objection in situations they deem immoral. The erosion of this right is bolstered by the doctrine of "physician value neutrality" (PVN) which may be an impetus for the push to require physicians to refer for procedures they find immoral. It is only a small step from referral to compelling performance of these same procedures. If no one particular value is more morally correct than any other (a foundational PVN premise) and a physician ought to be value neutral, than conscientious objection to morally objectionable actions becomes a thing of the past. However, the argument for PVN fails. Therefore, Christian physicians should state their values openly, which would allow patients the ability to choose like-minded physicians. Some possible responses to this erosion of conscientious objection include, disengagement from non-Christian institutions, the formation of distinctly Christian medical institutions and political action. However, for the Christian the initial focus should be on a life of holiness which requires each of us to avoid evil.


Ectoparasites of sheep in three agro-ecological zones in central Oromia, Ethiopia.
A cross-sectional study was conducted to determine the prevalence and risk factors for ectoparasites infestation in sheep in three agro-ecological zones in central Oromia, Ethiopia, from October 2009 to April 2010. The study revealed that 637 (48.1%) of the 1325 sheep examined were infested with one or more ectoparasites. The ectoparasites identified were Bovicola ovis (27.2%), Melophagus ovinus (16.4%), Ctenocephalides sp. (2.3%), Linognathus africanus (1.2%), Linognathus ovillus (0.3%), Sarcoptes sp. (1.2%), Amblyomma variegatum (4.4%), Rhipicephalus evertsi evertsi (1.9%), Rhipicephalus pravus (1.9%), Rhipicephalus (Boophilus) decoloratus (1.1%), Rhipicephalus sanguineus (0.9%), Rhipicephalus praetextatus (1.1%) and Hyalomma truncatum (1.6%). Statistically significant difference was observed in prevalence of B. ovis amongst study agroecological zones: highland 36.6%, midland 20.9% and lowland 14.0%. Significantly higher prevalence was recorded in highland agroecological zone. A significantly (OR = 0.041, p < 0.001) higher prevalence of M. ovinus in the highland (31.7%) than in both the lowland (0%) and midland (1.9%) was observed. The risk of tick infestation in the lowland and midland was 9.883 times and 13.988 times higher than the risk in the highland, respectively. A significantly higher prevalence of Ctenocephalides species was encountered in both the lowland (OR = 4.738, p = 0.011) and midland (OR = 8.078, p = 0.000) than in the highland agro-ecological zone. However, a significant difference (p = 0.191) amongst agro-ecological zones was not found for the prevalence of Linognathus and Sarcoptes species. Statistically significant variation (p > 0.05) was never recorded in the prevalence of all the identified species of ectoparasites between male and female sheep hosts. However, a significantly (p = 0.006) higher prevalence of B. ovis was recorded between young and adult sheep. The risk of B. ovis infestation was 1.45 times higher in young than the adult sheep. Furthermore, a significantly (p < 0.001) higher prevalence of M. ovinus, B. ovis and Sarcoptes sp. was found between sheep with poor and a good body condition. The ever increasing threat of ectoparasites on overall sheep productivity and tanning industry in Ethiopia warrants urgent control intervention. Further studies on the role of ectoparasites in transmission of diseases to sheep, zoonotic importance, comparative prevalence and load, and the importance of sheep as alternative hosts in different agroecological zones, breeds and management systems in Ethiopia are recommended so as to design applicable control programme in the country.


Naloxone inhibits not only stress-induced analgesia but also sympathetic activation and baroreceptor-reflex sensitivity.
Interactions between the sympathetic nervous system and pain are manifold and still have not been sufficiently characterized. Accordingly, several possible neuronal pathways have been described as being involved in mental stress-induced analgesia. We studied the role of the endogenous opioidergic system in stress-induced analgesia in 14 healthy participants in a double-blind cross-over trial. Naloxone or placebo was applied while electrical pain stimulation was started and electrical current increased. After reaching a constant stimulation at 30 mA, a color word interference test (Stroop task) was performed in a stressful and a non-stressful version. Blood pressure, heart rate and baroreflex sensitivity were continuously recorded to assess autonomic activation. Each participant was tested with naloxone and placebo with a randomized and balanced order of trials. The major results are that the opioid-receptor antagonist naloxone prevented (1) stress-induced reduction of tonic current-induced pain, (2) attenuated the simultaneous activation of the sympathetic nervous system, and (3) reduced the counteraction of sympathetic activation by vagal baroreceptor mechanisms. Thus, the opioidergic system not only modulates nociceptive input but also the interplay with vegetative responses. We conclude that acute stress, sympathetic activation and analgesia might be linked via vagal reflexes, which are disturbed when opioid receptors are blocked. This mechanism might underlie increased perception of noxious stimuli in patients with chronic pain or mood disorders.


An alpha2-macroglobulin associated factor produced by T lymphocytes which provides polyclonal stimulation of B lymphocytes to maintain the turnover of their surface Ig.
The supernatant of 'crowded' but not 'spread' rabbit spleen cell cultures contains a macroglobulin factor which behaves in an Ig-turnover assay as any T-independent antigen or polyclonal B-cell activator (PBA). In the supernatants of crowded rabbit lymphoid cell cultures prepared in serum free medium, the factor was found to be associated entirely with the alpha-macroglobulin (alpha M) fraction (alpha 1 + alpha 2). This alpha M was most probably actively secreted by the lymphocytes because: (i) sequential supernatants obtained in serum free medium of crowded cultures contained equal amounts of alpha M as well as equal PBA activity; (ii) the alpha M became labelled when the cells were grown in medium containing a radioactive amino acid. Macrophages were not required for the production of PBA. PBA was not produced when either crowded B or T cells were cultured alone but only when they were cultured together. Purified T cells were not triggered by any plant lectin to produce PBA. By use of anti-alpha 2M allotype antibodies and B and T cells from different rabbits, the PBA was shown to have the allotype of the T-cell donor. The PBA was associated with rabbit alpha 2M but not alpha 1M. We concluded that upon close contact, B cells stimulate T cells to produce a PBA associated with alpha 2M.


[Trials of artificial vaginas for bulls (author's transl)].
Introduction of short artificial vaginas with smooth plastic inner liners and without any internal pressure reduced the bacterial contamination of bull semen to a very considerable extent. Moreover, semen production increased, partly because of lower semen losses in short artificial vaginas with smooth inner liners which were not under pressure, partly because more intensive sexual preparation of the bulls was required to collect semen with this type of artificial vagina. When adequate sexual preparation of the bulls is practised, all bulls will accept short artificial vaginas with smooth inner liners which are not under pressure. The use of particularly rough rubber inner liners in artificial vaginas for bulls and using long artificial vaginas with internal pressure is not advisable because of unnecessarily high semen losses in the artificial vagina and unnecessary contamination of the crude semen.