Fracture prediction models for osteoporosis prevention.
Fracture prediction models have been developed that can estimate an individual's cumulative or lifetime fracture risk on the basis of bone mineral measurements and other factors. Examples illustrate how estimates of cumulative fracture risk might be influenced by initial age and level of bone mass, as well as by anticipated bone loss rate. New data regarding bone loss rates, fracture costs, and fracture risk factors should be incorporated to improve the accuracy of existing models. Such models could then be used for cost-benefit analysis to explore optimal treatment strategies.


Clinical manifestations of brucellosis in cattle of the southern Darfur Province, western Sudan.
Ninety-seven adult Zebu cattle with hygromas, 32 with arthritis and two showing long calving intervals were investigated for brucellosis. 92 per cent of hygromatous cattle, 62 per cent of arthritic cattle and both animals having long calving intervals were serologically positive and 65 per cent of milk samples were positive by the Milk Ring Test. Hygromas were found on the jaw, bursa, thigh, flank, hip, shoulder, neck and joints. Hygroma aspirates gave higher titres than sera in the serum agglutination test. IgG1, IgG2 and IgA were detected in all the aspirates and all but one contained IgM. Cattle with hygromas are a potential source of infection to other animals and a serious public health problem.


Polysynaptic activation of the dentate gyrus of the hippocampal formation: an olfactory input via the lateral entorhinal cortex.
The possibility that olfactory input is transmitted to specific subregions of the hippocampal formation via the entorhinal cortex was investigated electrophysiologically by analyzing the laminar profiles of potentials evoked in the hippocampal formation by stimulation of the lateral olfactory tract (LOT). LOT stimulation resulted in long latency (14--20 ms) evoked responses in the dentate gyrus of the hippocampal formation ipsilateral to the stimulation. The variable long latency of these responses and their inability to follow stimulus rates of 40/s suggested that these potentials reflected polysynaptic activation. Analysis of the laminar profiles of the evoked potentials indicated that the responses originated from a synaptic field localized in the outer portion of the stratum moleculare of the dentate gyrus, a terminal distribution which overlaps that of the lateral entorhinal cortical (LEC) projection to the dentate gyrus. Lesions of the LEC eliminated the long latency responses in the dentate gyrus evoked by LOT stimulation. In addition, a conditioning pulse delivered either to the LOT or to the LEC produced paired pulse potentiation of the response elicited by subsequent stimulation of the other structure. No evidence was found to indicate that responses were generated in regio superior of the hippocampus proper following LOT stimulation. Taken together, these results suggest that stimulation of the LOT activates the dentate gyrus of the hippocampal formation by multisynaptic pathways which relay through the lateral portion of the entorhinal area. This finding is discussed with regard to entorhinal cortical organization and the known olfactory projections to the LEC.


Effects of temperature, ionic strength and pH on the function of skeletal muscle myosin from a eurythermal fish, Fundulus heteroclitus.
The mummichog, Fundulus heteroclitus, is an intertidal fish that exhibits little change in swimming ability despite large and rapid variations in environmental parameters. We therefore tested the hypothesis that this nearly constant function is due to Fundulus myosin being intrinsically insensitive to changes of temperature, ionic strength and pH. In vitro motility assays were used to quantify the speed of unregulated actin filaments on myosin purified from F. heteroclitus glycolytic skeletal muscle. Filament speed was 2.07+/-0.17 microm s(-1) at 26 degrees C, ionic strength (Gamma/2) of 0.08 M Gamma/2 and pH 7.4. Speed increased as temperature increased over the range of 5-36 degrees C with an activation energy (E (a)) of 94.0+/-7.0 kJ mol(-1)) and an enthalpy (DeltaH (double dagger)) of 91.5+/-7.0 kJ mol(-1) at 20 degrees C. A linear relationship between temperature and ATPase activity was also obtained with actin-activated myosin Mg(2+)-ATPase assays over the temperature range 5-35 degrees C with E (a=)59.9+/-2.4 kJ mol(-1) and DeltaH (double dagger)=57.4+/-2.4 kJ mol(-1) at 20 degrees C. There was little or no effect of ionic strength on filament speed over the range 0.19 M Gamma/2-0.54 M Gamma/2. Speed increased significantly at lower ionic strengths and was 7.9-fold higher at 0.08 M Gamma/2 than at 0.19 M Gamma/2. Speed increased with pH with a 16-fold increase between pH 6.7 and 7.4. These results indicate that changes in physiological parameters that include temperature, pH and ionic strength affect the function of unregulated F. heteroclitus myosin, and thus other factors must be responsible for the mummichog's swimming performance being comparatively insensitive to environmental variation.


Hereditary spherocytosis in the elderly.
Five patients with hereditary spherocytosis diagnosed in their seventh to ninth decades of life are presented. These patients are remarkable for absent or mild clinical manifestations of disease. Splenectomy is the recommended treatment for hereditary spherocytosis to avoid the complications of aplastic or hemolytic crisis. When the diagnosis is made in the elderly, the treatment of choice may be careful observation with folic acid supplementation rather than splenectomy. This recommendation is based on the incidence of complications of splenectomy in the elderly in comparison to the severity and incidence of complications from the disease itself.


A case of acute subdural hematoma due to ruptured aneurysm detected by postmortem angiography.
Acute subdural hematoma (ASDH) is mostly caused by head trauma, but intrinsic causes also exist such as aneurysm rupture. We describe here a case involving a man in his 70s who was found lying on the bedroom floor by his family. CT performed at the hospital showed ASDH and a forensic autopsy was requested. Postmortem cerebral angiography showed dilatation of the bifurcation of the middle cerebral artery, which coincided with the dilated part of the Sylvian fissure. Extravasation of contrast medium into the subdural hematoma from this site was suggestive of a ruptured aneurysm. Autopsy revealed a fleshy hematoma (total weight 110 g) in the right subdural space and findings of brain herniation. As indicated on angiography, a ruptured saccular aneurysm was confirmed at the bifurcation of the middle cerebral artery. Obvious injuries to the head or face could not be detected on either external or internal examination, and intrinsic ASDH due to a ruptured middle cerebral artery aneurysm was determined as the cause of death. One of the key points of forensic diagnosis is the strict differentiation between intrinsic and extrinsic onset for conditions leading to death. Although most subdural hematomas (SDH) are caused by extrinsic factors, forensic pathologists should consider the possibility of intrinsic SDH. In addition, postmortem angiography can be useful for identifying vascular lesions in such cases.


Activation and peroxisomal beta-oxidation of fatty acids and bile acid intermediates in liver from Bombina orientalis and from the rat.
1. Bombina orientalis excretes mainly C27 bile acids: trihydroxycoprostanic and varanic acids. More than 90% of the trihydroxycoprostanic acid (THCA) present in the bile, was conjugated with taurine; varanic acid was present in the unconjugated form. 2. Trihydroxycoprostanoyl-CoA (THC-CoA) synthetase activity, required for the formation of the taurine conjugate, was present in the liver of Bombina orientalis. 3. Peroxisomal beta-oxidation, which catalyzes the oxidation of fatty acids as well as the conversion of C27 bile acids into C24 bile acids in rat and human liver, could be detected in liver of Bombina orientalis when palmitoyl-CoA was used as substrate, but not when trihydroxycoprostanoyl-CoA (THC-CoA) was used.


Multidisciplinary approach to the management of dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans (DFSP) is the most common cutaneous sarcoma. Tentacle-like extensions of neoplastic cells create a high incidence of local recurrence and pose challenges to resection and reconstruction. Here we present a multidisciplinary approach to the management of DFSP incorporating the expertise of a Mohs micrographic surgeon, surgical oncologist, dermatopathologist, and plastic surgeon. This was a single-institution, retrospective review of a prospectively maintained database of 19 consecutive patients who underwent resection and reconstruction of a DFSP from 1998 to 2010. All patients underwent Mohs micrographic surgery for mapping of peripheral margins (stage I excision), followed by wide local excision for delineation of the deep margin (stage II excision). Procedures were performed in consultation with a dermatopathologist who confirmed tumor-free margins, and a plastic surgeon who performed immediate reconstruction after the wide local excision (stage II reconstruction). Nineteen patients were included in this study. The average number of Mohs stages required for clearance of peripheral margins was 2.7 ± 0.7. The mean time between stage I and II procedures was 16 ± 11 days. The average defect size after the stage II operation was 87.3 cm(2) (range, 9-300 cm(2)). There were no cases of tumor recurrence. Mean follow-up time was 17 months (range, 1-53 months). This is a retrospective review of a single-institution experience. A multidisciplinary approach to the management of DFSP optimizes both oncologic and reconstructive outcomes, minimizing the risk for local recurrence and limiting the functional and cosmetic morbidity associated with surgical resection.


Role of Friend-associated lymphatic leukemia virus in immunization against Friend leukemia complex.
Mice inoculated with Friend leukemia complex (FLC) pretreated with concanavalin A are resistant to FLC challenge only when they have become infected with the FLC-associated lymphatic leukemia virus (LLV). In interpreting states of resistance to FLC induced by various immunizing procedures, the possibility that immunity is sustained by an unrecognized LLV infection should always be considered.


Crossover Effects in Lithium-Metal Batteries with a Localized High Concentration Electrolyte and High-Nickel Cathodes.
While crossover effects, such as transition-metal dissolution, are well-understood in lithium-ion batteries, there is a limited understanding of the effect of crossed-over chemical species in cells with oxide cathodes and lithium-metal anodes. In this work, the effects of cathode-to-anode and anode-to-cathode crossover are explored in cells with a high-nickel cathode, lithium-metal anode, and a localized high-concentration electrolyte (LHCE). Dramatic differences are found among cells; a lithium-metal anode paired with a high-nickel cathode has three times less solid-electrolyte interphase growth than a lithium-metal anode paired with lithium metal. Meanwhile, the cathode paired with lithium metal has 2-3 times higher capacity fade than the same cathode paired with graphite. Decomposition and crossover of the FSI salt is identified as the main source of these changes. The fluorine in the salt is first stripped off at the lithium-metal anode, and the remaining sulfur and nitrogen cross over to the cathode. Although the reduction in fluorine content harms the surface stability of the cathode, the lithium-metal anode benefits from the increased fluorine content. Because the lithium-metal anode is typically the bottleneck for cells with thin lithium, crossover is a major factor in the enhanced performance of lithium-metal batteries with LHCE.


Frontiers of fractals for complex systems: recent advances and future challenges.
This special issue of the European Physical Journal Special Topics titled "Frontiers of Fractals for Complex Systems: Recent Advances and Future Challenges" is a collection of cutting-edge research proposing the application of fractal features to the dynamics of highly nonlinear complex systems.


Performance, process kinetics and functional microbial community of biocatalyzed electrolysis-assisted anaerobic baffled reactor treating carbohydrate-containing wastewater.
In this study, an anaerobic baffled reactor (ABR) coupled with a microbial electrolysis cell (MEC) was set up to treat carbohydrate-containing wastewater at 55 ± 1 °C. The MEC was employed to accelerate the degradation of volatile fatty acids (VFAs). The removal of chemical oxygen demand (COD) and production of methane and the corresponding kinetics were determined for different organic load rates (OLRs). The highest COD removal rate was 95.8% at an OLR of 7.0 kg COD m-3 d-1, but it declined to 90.4% when the OLR was 19.4 kg COD m-3 d-1 and finally stabilized at 65.3% when the OLR was increased to 34.3 kg COD m-3 d-1. The volumetric production of methane was 1.5 L (L-1 d-1) when the OLR was 7.0 kg COD m-3 d-1 and increased to 4.1 L (L-1 d-1) at an OLR of 34.3 kg COD m-3 d-1, when the methane yield stabilized at 0.20-0.25 L g-1 CODremoved. The kinetics and predictions according to the Stover-Kincannon and Van der Meer-Heertjes models closely agreed with the experimental data for the removal of COD and volumetric production of methane, respectively. An analysis of the microbial community suggested that hydrolytic bacteria, syntrophic fatty acid-oxidizing bacteria (SFOB), exoelectrogens and hydrogenotrophic methanogens achieved a significant synergistic effect and enhanced the degradation of VFAs, which made the thermophilic anaerobic system stable and efficient at high OLRs.


Single molecule study of the intrinsically disordered FG-repeat nucleoporin 153.
Nucleoporins (Nups), which are intrinsically disordered, form a selectivity filter inside the nuclear pore complex, taking a central role in the vital nucleocytoplasmic transport mechanism. These Nups display a complex and nonrandom amino-acid architecture of phenylalanine glycine (FG)-repeat clusters and intra-FG linkers. How such heterogeneous sequence composition relates to function and could give rise to a transport mechanism is still unclear. Here we describe a combined chemical biology and single-molecule fluorescence approach to study the large human Nup153 FG-domain. In order to obtain insights into the properties of this domain beyond the average behavior, we probed the end-to-end distance (R(E)) of several ∼50-residues long FG-repeat clusters in the context of the whole protein domain. Despite the sequence heterogeneity of these FG-clusters, we detected a reoccurring and consistent compaction from a relaxed coil behavior under denaturing conditions (R(E)/R(E,RC) = 0.99 ± 0.15 with R(E,RC) corresponding to ideal relaxed coil behavior) to a collapsed state under native conditions (R(E)/R(E,RC) = 0.79 ± 0.09). We then analyzed the properties of this protein on the supramolecular level, and determined that this human FG-domain was in fact able to form a hydrogel with physiological permeability barrier properties.


Primary central neurocytoma of the mesencephalic tectum in a pediatric patient.
Neurocytomas are tumors or neuronal differentiation, typically located within the supratentorial ventricular system. The extraventricular location is uncommon. A limited number of cases involving the brainstem have been reported and may be misdiagnosed as brainstem gliomas. Furthermore, midbrain neurocytomas are extremely rare, and no similar cases in pediatric patients have been reported in the literature to date. Brainstem location of neurocytomas often precludes gross total removal of the lesion, and in these cases, adjuvant therapies may be helpful. We report a case of a 16-year-old child who presented with signs and symptoms of increased intracranial pressure. The magnetic resonance imaging study demonstrated the presence of a primary mesencephalic tectum lesion causing obstructive hydrocephalus. The patient underwent emergent ventriculoperitoneal shunt implantation, resolving the hydrocephalus and the clinical symptoms. The lesion was partially removed through a suboccipital craniotomy and supracerebellar infratentorial approach to the mesencephalic tectum, without intraoperative complications. Histological examination of the lesion was consistent with the diagnosis of extraventricular neurocytoma. The patient was referred to the oncology department for additional treatment with Gamma Knife radiosurgery. Although brainstem neurocytoma is rare, this case demonstrates that it should be included in the differential diagnosis of brainstem gliomas. Because of brainstem tumor location, complete surgical removal may be challenging or not possible, with a high risk of postoperative neurological deficits. Adjuvant therapies may prevent local tumor growth in cases of tumor remnants or recurrences following microsurgery in selected cases.


Camel Bite Injury to the Face in an Adult Patient: Skin Closure Controversy.
Animal bite injuries are prevalent worldwide. Camel bites, as a cause, are relatively rare. Male camels are particularly aggressive, especially during the rutting season. These injuries, when inflicted over the face, have a disfiguration effect with possible psychological repercussions to the patient. The surgical management of facial camel bite is described sporadically and remains a source of deliberation. Our paper reports the mechanism and management of facial soft tissue injury inflicted by camel bite over the face in an adult male with long-time follow-up for the patient post surgical repair without any documented complications. This case report demonstrates the complex nature of camel bite injuries over the face. Inappropriate wound management may result in long-term sequelae, which may affect the patient's quality of life. Individuals should apply caution when dealing with camels, mainly in the rutting season. Primary skin closure, especially to the face or neck, and proper wound management will decrease the risk of permanent scars and infections.


Synchronous papillary mucinous adenocarcinoma of the endocervix and fallopian tubes.
A unique case of synchronous, trifocal mucinous papillary adenocarcinoma involving the uterine cervix and both fallopian tubes is presented. Unequivocal carcinoma in situ changes are demonstrated in all three primary sites. A discussion of synchronous development of malignancies of the female genital tract and differentiation from contiguous or metastatic spread of a single primary focus follows.


Gas exchange in acute lung injury.
The predominant mechanism of abnormal gas exchange in patients with the adult respiratory distress syndrome is intrapulmonary shunting. However, other abnormalities of cardiopulmonary function may modify the degree of hypoxemia that is seen, and must be considered when interpreting the effect of therapy.


Dealing with aggressive methadone patients in community pharmacy: a critical incident study.
Community pharmacists are an important link between methadone patients and the health service in the United Kingdom. However, many pharmacists feel ill prepared to deal with methadone patients, with aggressive behavior a particular concern. To assess the perceived impact of methadone patient aggression on pharmacy practice. Sixteen registered pharmacists with a minimum of 3 years' work experience were recruited from within 3 Scottish health boards. Critical incident interviews were conducted to assess pharmacist behavior during an interaction with an aggressive methadone patient. Factors considered by pharmacists to have a negative impact on an interaction with an aggressive methadone patient included intoxication of the patient, the presence of a new or an inexperienced pharmacist, and a restricted time frame for dispensing methadone. Positive factors when dealing with aggressive patients were authoritative behavior by the pharmacist, a separate dispensing area for methadone patients, or a solid counter and a positive relationship between pharmacist and patient. Aggression from methadone patients is a risk when dispensing methadone. However, action can be taken by the pharmacist to minimize the impact of that aggression on pharmacy practice. The provision of further training and support, particularly to inexperienced pharmacists, could further reduce the negative impact of patient aggression. The present study indicates that such training could be based on nontechnical skills to strengthen current leadership and teamwork behaviors.


Diversity of parasite complex II.
Parasites have developed a variety of physiological functions necessary for completing at least part of their life cycles in the specialized environments of surrounding the parasites in the host. Regarding energy metabolism, which is essential for survival, parasites adapt to the low oxygen environment in mammalian hosts by using metabolic systems that are very different from those of the hosts. In many cases, the parasite employs aerobic metabolism during the free-living stage outside the host but undergoes major changes in developmental control and environmental adaptation to switch to anaerobic energy metabolism. Parasite mitochondria play diverse roles in their energy metabolism, and in recent studies of the parasitic nematode, Ascaris suum, the mitochondrial complex II plays an important role in anaerobic energy metabolism of parasites inhabiting hosts by acting as a quinol-fumarate reductase. In Trypanosomes, parasite complex II has been found to have a novel function and structure. Complex II of Trypanosoma cruzi is an unusual supramolecular complex with a heterodimeric iron-sulfur subunit and seven additional non-catalytic subunits. The enzyme shows reduced binding affinities for both substrates and inhibitors. Interestingly, this structural organization is conserved in all trypanosomatids. Since the properties of complex II differ across a wide range of parasites, this complex is a potential target for the development of new chemotherapeutic agents. In this regard, structural information on the target enzyme is essential for the molecular design of drugs. This article is part of a Special Issue entitled: Respiratory complex II: Role in cellular physiology and disease.


Isolation of azole-resistant Aspergillus fumigatus from imported plant bulbs in Japan and the effect of fungicide treatment.
Increasing numbers of azole-resistant Aspergillus fumigatus (ARAf) in the environment have become a global public health issue. We surveyed tulip bulbs that were imported from the Netherlands and found that 6.3-15.8% of bulbs were contaminated by ARAf with a tandem-repeat mutation in the promoter region of the cyp51A gene. We also showed that fungicide treatment of the tulip bulbs by benomyl or prochloraz effectively reduced the rate of isolation. This is the first report demonstrating a method of eliminating human fungal pathogens from plant bulbs.


Profile diversity of galacto-oligosaccharides from disaccharides to hexasaccharides by porous graphitic carbon liquid chromatography-orbitrap tandem mass spectrometry.
Galacto-oligosaccharides (GOS) are important prebiotic supplements for commercial nutraceutical food. The prebiotic efficacy of functional GOS is dependent on their chemical profile. Screening potential markers aids specifications and quality control of GOS materials. However, profiling analysis of GOS with a degree of polymerization (DP) ≥ 4 is still challenging. This study presents a porous graphitic carbon liquid chromatography-orbitrap tandem mass spectrometry-based method that characterized 58 linear and 10 branched GOS and detected 59 non-reducing GOS from DP2 to DP6. The results indicated that 15 major group components with DP2-DP5 accounted for more than 65% of total GOS content in GOS samples, while non-reducing GOS components accounted for only 2.8-7.6%. Substantial variations in components occurred in samples from different batches and sources. Structural and constitutive diversity were dominated by DP3-DP5. This method can help control the quality of GOS products and be used to investigate the structural and prebiotic-efficacy relationships.


[CNGOF Guidelines for Clinical Practice: Revision of the Methodology].
To revise the organization and the methodology of the Practice Clinical Guidelines (PCG) of the French College of Gynecologists and Obstetricians (CNGOF). The different available methods of PCG organization and of scientific evidence grading have been consulted after searching in the Medline database. The PCG group of the CNGOF has decided to adopt the AGREE II (for Appraisal of Guidelines for REsearch and Evaluation) methology for PCG organization and the GRADE (for Grading of Recommendation Assessment, Development, and Evaluation) system for grading scientific evidence. By adopting the AGREE II consortium criteria and grading scientific evidence according to the GRADE system, the CNGOF will increase the quality of the overall process, will deliver more targeted and easy to assimilate recommendations, to facilitate professional decision making.


Controlling seepage in discrete particle simulations of biological systems.
It is now commonplace to represent materials in a simulation using assemblies of discrete particles. Sometimes, one wishes to maintain the integrity of boundaries between particle types, for example, when modelling multiple tissue layers. However, as the particle assembly evolves during a simulation, particles may pass across interfaces. This behaviour is referred to as 'seepage'. The aims of this study were (i) to examine the conditions for seepage through a confining particle membrane and (ii) to define some simple rules that can be employed to control seepage. Based on the force-deformation response of spheres with various sizes and stiffness, we develop analytic expressions for the force required to move a 'probe particle' between confining 'membrane particles'. We analyse the influence that particle's size and stiffness have on the maximum force that can act on the probe particle before the onset of seepage. The theoretical results are applied in the simulation of a biological cell under unconfined compression.


Population differences in the timing of diapause: a test of hypotheses.
The reproductive phenology of the freshwater copepod Diaptomus sanguineus differs markedly between populations residing in two Rhode Island ponds. In a permanent pond the population switches abruptly from making subitaneous (immediately hatching) eggs to diapausing eggs at the end of March each year. In contrast, a temporary pond population switches egg types in May, returns to production of subitaneous eggs in June, and concludes the reproductive season by making diapausing eggs in July. An ESS model suggests that the pattern of diapause expected of a copepod population is a function of annual variation in the onset of harsh conditions (catastrophe date). When variation is relatively low, the superior strategy is for diapause to begin a constant period before the mean catastrophe date. When variation is high, females should make first subitaneous eggs and then diapausing eggs irrespective of the expected catastrophe date. With discrete generations, such a population would alternate between egg types. In the permanent pond, variation of catastrophe date the spring onset of planktivory by sunfish is low, whereas in the temporary pond variation of the catastrophe (pond drying) is high. The model predicts well the phenology of the two copepod populations.In the research reported here, we tested the hypothesis that copepods from the permanent pond, which switch to diapause at the same time every year, are cued by the environment to begin diapause (i.e. by photoperiod, temperature, or both), whereas those from the temporary pond make both egg types regardless of environmental conditions. In opposition to our hypothesis, experimental results indicate that diapause in both populations is cued by the environment. The distinct reproductive phenologies documented in the two populations apparently result from the copepods responding to different environmental cues, rather than one being responsive to the environment while the other is not.


Quantitative evaluation of DNA double-strand breaks (DSBs) through single-molecule observation.
By adapting the method of single molecular observation for individual DNAs, it will be shown that reliable analysis of double-strand breaks, DSBs, becomes possible for various kinds of damage sources. Single DNA above the size of several-tens kilo base-pairs exhibits the length scale above several μm, indicating that their whole conformation is visible with fluorescence microscopy by adding suitable fluoresce dye to the solution. Various examples of the quantitative evaluation on DSBs are described, together with the evaluation of the protective effects of anti-oxidants.


Intention to adopt a healthy diet among women with and without a history of gestational diabetes: Constructs and beliefs from the theory of planned behavior.
Women with a history of gestational diabetes (GDM) have difficulty maintaining a healthy diet after delivery. The theory of planned behavior (TPB) is effective in identifying the determinants of adopting a healthy diet. The objectives were to identify the determinants of the intention to adopt a healthy diet among the TPB constructs in women with (GDM+) and without (GDM-) a history of GDM, and to identify the beliefs associated with these constructs. The study was conducted in Québec (Canada) between 2009 and 2017. Data from 213 GDM+ and 91 GDM- women were analyzed. Women completed a questionnaire on the determinants of intention to adopt a healthy diet, defined as adherence to 2007 Canada's Food Guide. The subjective norm and perceived behavioral control (PBC) constructs were associated with the intention to adopt a healthy diet among GDM+ women (β = 2.21 and β = 4.37, respectively, p < 0.0001), whereas among GDM- women, PBC was the only construct associated with intention (β = 0.78; p < 0.0001). More specifically among GDM+ women, the disapproval of a family member other than the partner (β = 1.49; p = 0.0005), not feeling capable of adopting a healthy diet with access to food treats (β = 1.58; p < 0.0001), lack of free time (β = 1.31; p = 0.002), lack of information about healthy eating (β = 1.02; p = 0.015) or lack of easy recipes to prepare (β = 0.84; p = 0.042) was associated with a lower intention to adopt a healthy diet. Overall, among GDM+ women, different beliefs related to the subjective norm and PBC could be targeted to improve the eating habits of this specific population.


Biomimetic periosteum-bone substitute composed of preosteoblast-derived matrix and hydrogel for large segmental bone defect repair.
Repairing large segmental bone defects above a critical size remains challenging with high risk of delayed union or even non-union. From the perspective of bone development and clinical experience, periosteum plays an indispensable role in bone repair and reconstruction. In this study, we explored the feasibility of using preosteoblast-derived matrix (pODM) as a biomimetic periosteum. By culturing MC3T3-E1 cell sheet on poly(dimethylsiloxane) and performing decellularization, an integral cell-free sheet of pODM could be readily harvested. Bone marrow mesenchymal stem cells (BMSCs) adhered and proliferated well on pODM. In addition, pODM exhibited a chemotactic effect on BMSCs in a concentration-dependent manner and also promoted osteogenic differentiation of BMSCs. Following that, pODM was wrapped around a gelatin methacryloyl (GelMA) hydrogel to construct an engineered periosteum-bone substitute. A rabbit radius segmental bone defect model was used to examine the bone repair efficacy of pODM/GelMA. Upon implantation of pODM/GelMA construct for 12 weeks, the critical-sized bone defects completely healed with remarkable full reconstruction of medullary cavity at the radial diaphysis. Together, this work proposes a high potency of using precursor cell-derived matrix as a biomimetic periosteum, which preserves the beneficial biological factors while avoids the limitations of using exogenous cells for bone regeneration. Combining precursor cell-derived matrix with hydrogel may provide a promising periosteum-bone biomimetic substitute for bone repair. STATEMENT OF SIGNIFICANCE: Repairing large segmental bone defects above a critical size remains challenging. As the periosteum plays an essential role in bone repair, this study aimed to explore the use of preosteoblast-derived matrix (pODM), harvested from decellularized MC3T3-E1 cell sheet, as a biomimetic periosteum to facilitate bone repair. We found that in vitro, pODM exhibited considerable chemotactic effect and osteogenic induction capability to bone marrow mesenchymal stem cells (BMSCs). In vivo, implantation of pODM/gelatin methacryloyl (GelMA) constructs as engineered periosteum-bone substitutes effectively repaired the critical-sized segmental bone defects at rabbit radius. Surprisingly, remarkable full reconstruction of medullary cavity at the diaphysis was achieved. Therefore, combining pODM with hydrogel may provide a promising biomimetic substitute for bone repair.


Consequence and therapy of primary tooth intrusion.
The consequences of primary tooth intrusion to the permanent successors are as follows: internal white enamel hypoplasy, external white or yellow-brown enamel hypoplasy, crown dilaceration and root angulation. Questions of therapy have also been discussed.


Intraoperative detection of lymph node micrometastasis with flow cytometry in non-small cell lung cancer.
We sought to determine whether cytokeratin-positive cells can be detected as markers of lymph node metastasis by using flow cytometry within a time frame suitable for intraoperative decision making in non-small cell lung cancer. Five lymph nodes from each of 20 patients with non-small cell lung cancer were randomly selected for study. Each node was divided longitudinally into 3 pieces: one piece for flow cytometry, one for immunohistochemical staining, and the last for conventional hematoxylin and eosin staining. In both flow cytometry and immunohistochemistry, cytokeratin-positive cells were detected with the fluorescein isothiocyanate-conjugated anti-cytokeratin antibody AE1/AE3. Cytokeratin-positive nodes were detected by means of flow cytometry within 40 minutes. Eight (8%) of the 100 lymph nodes from 4 (20%) of the 20 patients were deemed positive for metastasis on the basis of conventional histologic examination. By contrast, 33 (33%) lymph nodes from 13 (65%) patients were deemed positive on the basis of immunohistochemical cytokeratin staining, and 38 (38%) lymph nodes from 14 (70%) patients were deemed positive on the basis of flow cytometric cytokeratin-positive cell detection. All nodes deemed positive for metastasis on the basis of conventional and immunohistochemical methods were also positive on flow cytometry. Flow cytometry enables rapid intraoperative diagnosis of nodal metastasis in patients with non-small cell lung cancer. Flow cytometric detection of cytokeratin-positive cells within lymph nodes correlates with their immunohistochemical detection, and its level of sensitivity is greater than that of conventional histologic staining and about equal to that of immunohistochemical staining.


Effect of surgical intervention on circulating tumor cells in patients with squamous cell carcinoma of the head and neck using a negative enrichment technology.
The purpose of this study was to investigate the impact of surgical intervention on detection of circulating tumor cells (CTCs) in patients with squamous cell carcinoma of the head and neck (SCCHN.) METHODS: We utilized a negative depletion technique to identify cytokeratin (CK)-positive CTCs. The numbers of CTCs immediately before and after surgical resection were compared. Seventy-six blood samples from 38 patients with SCCHN were examined. Seventy-nine percent of the patients had CTCs detected before and after surgery. A total of 7.89% had no CTCs before surgery, yet had CTCs identified after surgery. Overall, 60.5% of patients had an increased number of CTCs/mL after surgery with a mean increase of 6.63-fold. A statistically significant increase in CTCs was seen after surgery (p = .02). The timing of sample collection in patients with SCCHN who have surgical intervention can potentially impact the number of CTCs identified. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1799-1803, 2016.


PRE- AND POST-OPERATIVE SELF-REPORTED FUNCTION AND QUALITY OF LIFE IN WOMEN WITH AND WITHOUT GENERALIZED JOINT LAXITY UNDERGOING HIP ARTHROSCOPY FOR FEMOROACETABULAR IMPINGEMENT.
Generalized joint laxity is more prevalent in women than men and may lead to poorer post-operative outcomes in select orthopedic populations. There are no studies examining peri-operative function in patients with generalized joint laxity (GJL) and femoroacetabular impingement (FAI). The purpose of this study was to determine the difference in perceived function and quality of life as measured by the Hip Outcome Score ADL subscale (HOS-ADL), International Hip Outcomes Tool (iHOT-33) and the Short Form 12-Item Health Survey (SF-12) in women with and without GJL prior to and six months after undergoing hip arthroscopy for FAI. Cohort Study. Peri-operative data were collected from women with FAI from November 2011-September 2014. Lax subjects were women with laxity scores ≥4/9 on the Beighton and Horan Joint Mobility Index; Nonlax subjects were women with laxity scores <4/9. Functional outcomes were evaluated using the HOS-ADL, iHOT-33, PCS-12, and the MCS-12 pre-operatively and at 6 months post-operatively. Change scores (post-score - pre-score) were calculated for each outcome measure and compared between groups, along with pre-operative and post-operative means, using Mann-Whitney U tests. 166 women met the inclusion criteria: Nonlax (n = 131), Lax (n = 35). There were no statistically significant differences between groups in pre-operative functional outcomes (all p > .05). Additionally, there were no statistically significant differences between groups in post-operative means or change scores, respectively, for HOS-ADL (p = .696, .358), iHOT-33 (p = .550, .705), PCS-12 (p = .713, .191), and MCS-12 (p = .751, .082). Laxity score was not associated with any post-operative functional outcome score or change score (all p > .05). Women with and without generalized joint laxity do not appear to report differences in hip function in the 6-month peri-operative period before and after hip arthroscopy for FAI. 3.


Dose-dependent effects of vitamin D on transdifferentiation of skeletal muscle cells to adipose cells.
Fat infiltration within muscle is one of a number of features of vitamin D deficiency, which leads to a decline in muscle functionality. The origin of this fat is unclear, but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D₃, 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10⁻¹³, 10⁻¹¹, 10⁻⁹, 10⁻⁷ or 10⁻⁵ M) of 1,25(OH)₂D₃ for up to 6 days and markers of muscle and fat development measured. Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10⁻¹³ and 10⁻¹¹ M) of 1,25(OH)₂D3 increased fat droplet accumulation, whereas high physiological (10⁻⁹ M) and supraphysiological concentrations (≥10⁻⁷ M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10⁻¹³ and 10⁻¹¹ M) was associated with a sequential up-regulation of PPARγ2 (PPARG) and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10⁻⁹ M) reduced all these effects, and the highest concentration (10⁻⁵ M) appeared to have toxic effects. This is the first study to demonstrate dose-dependent effects of 1,25(OH)₂D₃ on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.


Polymer induced crystal organization of composite resins.
The elaboration of efficient dental resins requires a high degree of internal cohesion and a strong organization of the filler/matrix systems, and a good compatibility between the organic and inorganic constituents of the composite. Combining fractal aerosils and polymer constitutes an original way to realize promising dental composites. Determination of the combined roles of fractal fillers and polymers in the synthesis of composite resins, and the polymer dose in the crystal arrangement of the composite constituents, both being a requisite for the optimization of the filler/matrix compatibility. Poly(methyl methacrylate) was used to enhance the compatibility between the organic matrix composed of the (bisphenol A dimethacrylate+1,3-butanediol dimethacrylate) mixture, and the aerosil filler. The characteristics of the assemblage of the latter particles that was mediated by adsorbed polymer and resulted in the formation of dense sediments were determined. The macroscopic crystals that nucleated within the settled phases were analyzed in order to evidence their internal arrangement and cohesion by Differential Scanning Calorimetry. Atomic force microscopy was employed to reveal the surface texture. The association of fractal powders and polymer gives rise to agglomerated structures of high imbrications and cohesion. The polymer dose initially added to the aerosil particles suspended in the mixture was determined (i) to set the aerosil aggregation mechanism and, as a result, the aggregate size and porosity; (ii) to control the formation and characteristics of the settled phase; and (iii) to determine the crystal organization and the filler/matrix compatibility. The formation of hexagonal platelets incorporating the filler/polymer aggregates within the crystal organization demonstrates the high degree of compatibility of the different constituents of the composite that is mediated by the amount of polymer adsorbed at the aerosil/matrix interface.


The incidence of a new human cross-reactive idiotype linked to subgroup VHIII heavy chains.
Cross-reactive idiotypes (CRI) on human rheumatoid factors (RF), which are identified by murine monoclonal antibodies (mAb), have proved useful in defining both the incidence and the structural characteristics of these autoantibodies. In this study, a new murine anti-idiotypic reagent, mAb B6, has been used to identify and define the expression of a distinct heavy chain CRI. The B6 CRI was found on 20% of monoclonal IgM (16 of 81), but on only 5% of monoclonal IgA (1 of 20) and on no monoclonal IgG. In addition, this CRI was expressed exclusively on a subset of Ig derived from the VHIII protein variable region subgroup. In immunoblotting experiments, the mAb B6 bound directly to the heavy (H) chains of CRI positive proteins. The B6 CRI was found frequently on monoclonal IgM-RF molecules, and the mAb B6 could inhibit the binding of the RF to its IgG antigen. It was also demonstrated that Staphylococcus aureus protein A (SpA), which has recently been shown to bind to the F(ab) region of VHIII molecules, could block the interaction of some B6 CRI positive IgM to the anti-CRI. These experiments suggest that the B6 CRI is a marker for one or a few VHIII genes and that it is expressed commonly on IgM paraproteins, many of which have RF activity.


Isolation and Identification of Dengue Virus Interactome with Human Plasma Proteins by Affinity Purification-Mass Spectrometry.
Viral proteins evolve to benefit the interaction with host proteins during the infection and replication processes. A comprehensive understanding of virus interactome with host proteins may thus lead to the identification of molecular targets for infection inhibition. We present a procedure for isolating and identifying the dengue virus interactome with human plasma proteins. It comprises the fractionation of human plasma by anion exchange chromatography, followed by affinity purification and mass spectrometry identification of the captured proteins. This procedure was applied to the characterization of the interactions of the four serotypes of dengue virus with human plasma proteins, mediated by the domain III of the envelope protein of the virus. The resulting interactome comprises 62 proteins, six of which were validated as new direct interactions of the virus with its human host.


Talotibial exostoses with entrapment of the deep peroneal nerve.
An athlete with talotibial exostoses with entrapment of the deep peroneal nerve is presented. This diagnosis was made by history, physical and roentgenographic examinations, bone scan, and isokinetic exercising. Treatment of this condition involved surgical excision of the boney exostoses.


Non-vitamin K antagonist oral anticoagulants in very elderly east Asians with atrial fibrillation: A nationwide population-based study.
The evidence of effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (NOACs) among elderly East Asians is limited. We aimed to describe the effectiveness and safety outcomes associated with NOACs and warfarin among elderly Koreans aged ≥80 years. Using the Korean Health Insurance Review and Assessment service database, patients with atrial fibrillation (AF) who were naïve to index oral anticoagulant between 2015 and 2017 were included in this study (20,573 for NOACs and 4086 for warfarin). Two treatment groups were balanced using the inverse probability of treatment weighting (IPTW) method. The clinical outcomes including ischemic stroke, major bleeding including intracranial hemorrhage (ICH) and gastrointestinal bleeding (GIB), and a composite of these outcomes were evaluated. Compared to warfarin, NOACs were associated with lower risks of ischemic stroke (hazard ratio 0.74 [95% confidence interval 0.62-0.89]), and composite outcome (0.78 [0.69-0.90]). NOACs showed nonsignificant trends towards to lower risks of GIB and major bleeding than warfarin. The risk of ICH of NOAC group was comparable with the warfarin group. Among NOACs, apixaban and edoxaban showed better composite outcomes than warfarin. Among the clinical outcomes, only ischemic stroke and the composite outcome had a significant interaction with age subgroups (80-89 years and ≥90 years, P-for-interaction = .097 and .040, respectively). NOACs were associated with lower risks of ischemic stroke and the composite outcome (ischemic stroke and major bleeding) compared to warfarin in elderly East Asians. Physicians should be more confident in prescribing NOACs to elderly East Asians with AF.


Psychometric properties of the RAND-36 among three chronic diseases (multiple sclerosis, rheumatic diseases and COPD) in The Netherlands.
In this article, psychometric properties both of the total RAND-36 and of its subscales, such as unidimensionality, differential item functioning (DIF or item bias), homogeneity and reliabilities, are examined. The data from populations with three chronic illnesses, multiple sclerosis (n = 448), rheumatism (n = 336) and COPD (n = 259), have been collected in different parts of the Netherlands. The main technique used was Mokken scale analysis for polytomous items. All subscales of the RAND-36 appeared to be unidimensional. For the subscales 'mental health' and general health perceptions' some minor indications of DIF for the different chronic illnesses were found. Reliabilities of almost all subscales in all subpopulations were higher than 0.80, while the homogeneities of almost all subscales in all subpopulations were higher than 0.50, indicating 'strong unidimensional, hierarchical scales'. In general, the subscales of the RAND-36 can be used to compare persons with different chronic illnesses. The subscale 'general health perceptions' did not function as well as would be preferred.


Spine Treatment Appraisal Report (STAR): Interbody Fusion Does not Fully Protect Against Rod Failure in Long Posterior Spinal Fusion for Adult Spinal Deformity.
El Dafrawy M, Bridwell K, Adogwa O, Shlykov M, Koscso J, Lenke LG, Lertudomphonwanit T, Kelly MP, Gupta M. Rod fractures and nonunions after long fusion to the sacrum for primary presentation adult spinal deformity: a comparison with and without interbody fusion in the distal lumbar spine. Spine Deform. 2020. doi: 10.1007/s43390-020-00 174-6. Online ahead of print. PMID: 32 725 494.


The Reliability of Oral and Pharyngeal Dimensions Captured with Acoustic Pharyngometry.
Acoustic Pharyngometry (APh) is a method for quantifying oropharyngeal tract configuration using sound wave reflection and is commonly used in diagnostics and research of sleep apnea. The standard preset output of APh (minimal cross-sectional area) has been established as reliable. However, by conducting post-processing measures on specific breathing tasks, APh data can also reveal oral length, oral volume, pharyngeal length, and pharyngeal volume. Given that these measures may have utility in dysphagia research, the reliability of these measures is unknown and is the focus of the current study. Ten young healthy female volunteers completed two sessions of APh data collection to obtain measures of oral length, oral volume, pharyngeal length, and pharyngeal volume 1 week apart. Two-way mixed intraclass correlation coefficients were calculated to establish intra-rater reliability, inter-rater reliability, and test-retest reliability. Results revealed excellent levels of agreement within and across raters for all oropharyngeal tract parameters. Levels of test-retest agreement for oral length and oral volume indicated these parameters are appropriate for monitoring change within an individual. All parameters were deemed to have acceptable test-retest values as outcome measures in group-level analysis.


Attentional and affective biases for attractive females emerge early in development.
Predominant experience with females early in development results in infants developing an attractive, female-like facial representation that guides children's attention toward and affective preferences for attractive females. When combined with increased interest in the other sex at puberty, these early emerging biases might help explain the robust prosocial and financial biases men exhibit toward attractive women during adulthood.


Field-in-field technique with intrafractionally modulated junction shifts for craniospinal irradiation.
To plan craniospinal irradiation with "field-in-field" (FIF) homogenization in combination with daily, intrafractional modulation of the field junctions, to minimize the possibility of spinal cord overdose. Lateral cranial fields and posterior spinal fields were planned using a forward-planned, step-and-shoot FIF technique. Field junctions were automatically modulated and custom-weighted for maximal homogeneity within each treatment fraction. Dose-volume histogram analyses and film dosimetry were used to assess results. Plan inhomogeneity improved with FIF. Planning with daily modulated junction shifts provided consistent dose delivery during each fraction of treatment across the junctions. Modulation minimized the impact of a 5-mm setup error at the junction. Film dosimetry confirmed that no point in the junction exceeded the anticipated dose. Field-in-field planning and modulated junction shifts improve the homogeneity and consistency of daily dose delivery, simplify treatment, and reduce the impact of setup errors.


A Comparison of Single Shot Adductor Canal Block Versus Femoral Nerve Catheter for Total Knee Arthroplasty.
The aim of this study was to compare perioperative analgesia provided by single-injection adductor canal block (ACB) to continuous femoral nerve catheter (FNC) when used in a multimodal pain protocol for total knee arthroplasty (TKA). A retrospective cohort study compared outcome data for 148 patients receiving a single-injection ACB to 149 patients receiving an FNC. The mean length of stay (LOS) in the ACB group was 2.67 (±0.56) and 3.01 days (±0.57) in the FNC group (P<0.0001). The median ambulatory distances for the adductor group were further than the femoral group for postoperative days 1 (P<0.0001) and 2 (P=0.01). Single-injection ACB offered similar pain control and earlier discharge compared to continuous FNC in patients undergoing TKA.


Gene expression profiling of hepatocarcinogenesis in a mouse model of chronic hepatitis B.
Hepatocellular carcinoma (HCC) is a common complication of chronic viral hepatitis. In support of this notion, we have reported that hepatitis B surface antigen (HBsAg)-specific CD8+ T lymphocytes critically contribute to inducing chronic liver cell injury that exerts high carcinogenic potential in a hepatitis B virus (HBV) transgenic mouse model. The dynamics of the molecular signatures responsible for hepatocellular carcinogenesis are not fully understood. The current study was designed to determine the serial changes in gene expression profiles in a model of chronic immune-mediated hepatitis. Three-month-old HBV transgenic mice were immunologically reconstituted with bone marrow cells and splenocytes from syngeneic nontransgenic donors. Liver tissues were obtained every three months until 18 months at which time all mice developed multiple liver tumors. Nitrative DNA lesions and hepatocyte turnover were assessed immunohistochemically. Gene expression profiles were generated by extracting total RNA from the tissues and analyzing by microarray. The nitrative DNA lesions and the regenerative proliferation of hepatocytes were increased during the progression of chronic liver disease. In a gene expression profile analysis of liver samples, the chemokine- and T cell receptor (TCR)-mediated pathways were enhanced during chronic hepatitis, and the EGF- and VEGF-mediated pathways were induced in HCC. Among these molecules, the protein levels of STAT3 were greatly enhanced in all hepatocyte nuclei and further elevated in the cytoplasm in HCC tissue samples at 18 months, and the levels of phosphorylated TP53 (p-p53-Ser 6 and -Ser 15) were increased in liver tissues. HBV-specific immune responses caused unique molecular signatures in the liver tissues of chronic hepatitis and triggered subsequent carcinogenic gene expression profiles in a mouse model. The results suggest a plausible molecular basis responsible for HBV-induced immune pathogenesis of HCC.


Natural presence of V179E and rising prevalence of E138G in HIV-1 reverse transcriptase in CRF55_01B viruses.
There is increasing evidence that naturally occurring HIV-1 genetic diversity can have an impact on drug resistance. Recently, our previous study has demonstrated the natural presence of the V179D and K103R/V179D mutations associated with resistance to nonnucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF65_cpx strains. The aim of this study is to investigate the presence of natural drug-resistance mutations (DRMs) in other HIV-1 subtypes or CRFs circulating in China. A total of 14,403 pol sequences from China were retrieved from the Los Alamos HIV Sequence Database, 10,041 of which were treatment naïve and presented substantial genetic diversity. Besides the natural presence of V179D and K103R/V179D in CRF65_cpx, the natural presence of V179E was found in CRF55_01B. In all but one of the 228 patients infected with CRF55_01B, NNRTI resistance mutation V179E was present and the combination of V179E and E138G was detected in 14 treatment-naïve patients, with a rate of 6.2%. A significant trend for increasing prevalence of E138G mutation in CRF55_01B strains over time was observed (p < .001). Phylogenetic analysis was conducted to clarify the epidemiological relationship of CRF55_01B strains. Most of the sequences containing E138G mutation scattered in the big CRF55_01B cluster, which indicated the rising prevalence of E138G was mainly due to multiple mutation events rather than local transmission clusters of a particular variant containing E138G mutation. Our findings highlight the importance of molecular surveillance of CRF55_01B strains and the urgent need for implementation of effective preventive measures to reduce the transmission of CRF55_01B.


Crystal structure of the YGR205w protein from Saccharomyces cerevisiae: close structural resemblance to E. coli pantothenate kinase.
The protein product of the YGR205w gene of Saccharomyces cerevisiae was targeted as part of our yeast structural genomics project. YGR205w codes for a small (290 amino acids) protein with unknown structure and function. The only recognizable sequence feature is the presence of a Walker A motif (P loop) indicating a possible nucleotide binding/converting function. We determined the three-dimensional crystal structure of Se-methionine substituted protein using multiple anomalous diffraction. The structure revealed a well known mononucleotide fold and strong resemblance to the structure of small metabolite phosphorylating enzymes such as pantothenate and phosphoribulo kinase. Biochemical experiments show that YGR205w binds specifically ATP and, less tightly, ADP. The structure also revealed the presence of two bound sulphate ions, occupying opposite niches in a canyon that corresponds to the active site of the protein. One sulphate is bound to the P-loop in a position that corresponds to the position of beta-phosphate in mononucleotide protein ATP complex, suggesting the protein is indeed a kinase. The nature of the phosphate accepting substrate remains to be determined.


5-HT induced accumulation of 3',5'-AMP and the phosphorylation of paramyosin in the ABRM of Mytilus edulis.
In Mytilus edulis 5-Ht induced relaxation of a muscle in catch is preceded by an increase in 3',5'-AMP content. In vitro two proteins of the contractile apparatus are phosphorylated by 3',5'-AMP dependent protein kinases. The 295000 dalton protein cannot be identified, the other one is paramyosin. Phosphorylated paramyosin inhibits actomyosin ATPase of smooth mollusc muscles at low and high Ca++ concentrations.


Contrast and luminance adaptation alter neuronal coding and perception of stimulus orientation.
Sensory systems face a barrage of stimulation that continually changes along multiple dimensions. These simultaneous changes create a formidable problem for the nervous system, as neurons must dynamically encode each stimulus dimension, despite changes in other dimensions. Here, we measured how neurons in visual cortex encode orientation following changes in luminance and contrast, which are critical for visual processing, but nuisance variables in the context of orientation coding. Using information theoretic analysis and population decoding approaches, we find that orientation discriminability is luminance and contrast dependent, changing over time due to firing rate adaptation. We also show that orientation discrimination in human observers changes during adaptation, in a manner consistent with the neuronal data. Our results suggest that adaptation does not maintain information rates per se, but instead acts to keep sensory systems operating within the limited dynamic range afforded by spiking activity, despite a wide range of possible inputs.


Acute Kidney Injury in Dogs and Cats.
Acute kidney injury can cause significant morbidity and mortality in dogs and cats. Knowledge of the pathophysiology of renal damage can be beneficial to prevention and treatment. There are many causes of acute kidney injury, and the prognosis for each can vary. Appropriate fluid therapy and monitoring are essential for treatment.


Regulation of the human catalytic subunit of telomerase (hTERT).
Over the past decade, there has been much interest in the regulation of telomerase, the enzyme responsible for maintaining the integrity of chromosomal ends, and its crucial role in cellular immortalization, tumorigenesis, and the progression of cancer. Telomerase activity is characterized by the expression of the telomerase reverse transcriptase (TERT) gene, suggesting that TERT serves as the major limiting agent for telomerase activity. Recent discoveries have led to characterization of various interactants that aid in the regulation of human TERT (hTERT), including numerous transcription factors; further supporting the pivotal role that transcription plays in both the expression and repression of telomerase. Several studies have suggested that epigenetic modulation of the hTERT core promoter region may provide an additional level of regulation. Although these studies have provided essential information on the regulation of hTERT, there has been ambiguity of the role of methylation within the core promoter region and the subsequent binding of various activating and repressive agents. As a result, we found it necessary to consolidate and summarize these recent developments and elucidate these discrepancies. In this review, we focus on the co-regulation of hTERT via transcriptional regulation, the presence or absence of various activators and repressors, as well as the epigenetic pathways of DNA methylation and histone modifications.


Yeast cell surface display system for determination of humoral response to active immunization with a monoclonal antibody against EpCAM.
Even though an immunogenic formulation of the murine monoclonal anti-EpCAM (epithelian cell adhesion molecule) antibody Mab 17-1A, has been shown to evoke a strong humoral immune response in both, monkey studies and early clinical trials, conventional anti-EpCAM ELISA could not identify anti-EpCAM immune response in relation to treatment with Mab17-1A. In contrast, usage of cellulose membranes prepared by SPOT technology presenting overlapping EpCAM peptides allowed the unequivocal determination of EpCAM related antibodies present in monkeys sera after immunization with IGN101. Based on such contradictory results, it was of high interest to compare obtained data to a different method for better assessment of their possible interpretation. Therefore, in the present studies, some EpCAM peptides, determined as reactive by binding of IgG isolated from sera of treated monkeys on membranes prepared by SPOT technology, were represented on yeast surface using the pYD1 yeast display vector system. Binding of biotinylated IgG from sera was detected with streptavidin-FITC and quantity of binding was determined by FACS measurement. Though using this completely different method, experiments with pre-immune and immune sera of four monkeys exemplarily are comparable to the results obtained by analysis with synthetic peptide arrays.


Dynamic contrast-enhanced magnetic resonance imaging: definitive imaging of placental function?
The placenta constitutes a complex circulatory interface between the mother and fetus, but the relationship between the maternal and fetal circulation is still very difficult to study in vivo. There is growing evidence that magnetic resonance imaging (MRI) is useful and safe during pregnancy, and MRI is increasingly used for fetal and placental anatomical imaging. MRI functional imaging is now a modern obstetric tool and has the potential to provide new insights into the physiology of the human placenta. Placental perfusion has been studied during the first pass of an MR contrast agent, by arterial spin labeling, diffusion imaging, T1 and T2 relaxation time measurement using echo-planar imaging, and by a combination of magnetization transfer with established stereological methods. The BOLD (blood oxygen level-dependent) effect offers new perspectives for functional MRI evaluation of the placenta.


Central corneal thickness in tilted disc syndrome.
: Earlier literature reports that abnormal optic disc shape or size seem to be closely associated with the shape or size of the cornea. Here we search for an association between the presence of tilted disc syndrome and the central corneal thickness. : Sixty-one eyes of 61 patients with tilted disc syndrome were included in the study. Sixty-one eyes of 61 subjects were chosen as controls. Corneal thickness was evaluated with ultrasound pachymetry from the central region after instillation of topical proparacaine hydrochloride and before the ophthalmologic examination. : The mean central corneal thickness in the tilted disc syndrome group was found to be 547.5 +/- 36.16 mum (median 546, range 467 to 638). The mean central corneal thickness in the control group was measured as 541.09 +/- 29.52 mum (median 540, range 500 to 627). There was no statistically significant difference in corneal thickness between the tilted disc syndrome group and control group (p = 0.218). : There seems to be no correlation between the central corneal thickness and the presence of tilted disc syndrome.


Living a tormented life: Caregivers' experiences of caring for a child with autism in Northeastern Thailand.
Caring for children with autism spectrum disorder (ASD) can be a demanding challenge to caregivers. The aim of this study was to learn what caring for children with ASD means to caregivers who live in rural Thailand. A hermeneutic phenomenological approach was used to analyze narrative data from interviews of five caregivers. Three themes emerged: (a) being sensitive to the word autism, (b) being trapped in a tunnel of distress, and (c) being the universe for the child. Healthcare professionals need to be sensitive to the caregivers' cultural customs in order to meet their expectations in a respectful way.


Clinical efficacy of denosumab, teriparatide, and oral bisphosphonates in the prevention of glucocorticoid-induced osteoporosis: a systematic review and meta-analysis.
Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide in the 2017 American College of Rheumatology (ACR) guidelines but have a series of shortcomings. This study aims to explore the efficacy and safety of teriparatide and denosumab compared with those of oral bisphosphonate drugs. We systematically searched studies included in the PubMed, Web of Science, Embase, and Cochrane library databases and included randomized controlled trials that compared denosumab or teriparatide with oral bisphosphonates. Risk estimates were pooled using both fixed and random effects models. We included 10 studies involving 2923 patients who received GCs for meta-analysis, including two drug base analyses and four sensitivity analyses. Teriparatide and denosumab were superior to bisphosphonates in increasing the bone mineral density (BMD) of the lumbar vertebrae [teriparatide: mean difference [MD] 3.98%, 95% confidence interval [CI] 3.61-4.175%, P = 0.00001; denosumab: MD 2.07%, 95% CI 0.97-3.17%, P = 0.0002]. Teriparatide was superior to bisphosphonates in preventing vertebral fractures and increasing hip BMD [MD 2.39%, 95% CI 1.47-3.32, P < 0.00001]. There was no statistically significant difference between serious adverse events, adverse events, and nonvertebral fracture prevention drugs. Teriparatide and denosumab exhibited similar or even superior characteristics to bisphosphonates in our study, and we believe that they have the potential to become first-line GC-induced osteoporosis treatments, especially for patients who have previously received other anti-osteoporotic drugs with poor efficacy.


Research status and future prospects of extracellular vesicles in primary Sjögren's syndrome.
Primary Sjögren's syndrome (pSS) is a diffuse connective tissue disease characterized by the invasion of exocrine glands such as lacrimal and salivary glands, abnormal proliferation of T and B lymphocytes, and infiltration of tissue lymphocytes. With the development of modern medicine, although research on the pathogenesis, diagnosis, and treatment of pSS has made significant progress, its pathogenesis has not been fully understood. Meanwhile, in the era of individualized treatment, it remains essential to further explore early diagnosis and treatment methods. Exosomes, small vesicles containing proteins and nucleic acids, are a subtype of extracellular vesicles secreted by various cells and present in various body fluids. Exosomes contribute to a variety of biological functions, including intercellular signal transduction and pathophysiological processes, and may play a role in immune tolerance. Therefore, exosomes are key to understanding the pathogenesis of diseases. Exosomes can also be used as a therapeutic tool for pSS because of their biodegradability, low immunogenicity and toxicity, and the ability to bypass the blood-brain barrier, implying the prospect of a broad application in the context of pSS. Here, we systematically review the isolation, identification, tracing, and mode of action of extracellular vesicles, especially exosomes, as well as the research progress in the pathogenesis, diagnosis, and treatment of pSS.


Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study [corrected].
Patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) may develop neurodegenerative conditions associated with substantia nigra dysfunction such as Parkinson's disease. In patients with Parkinson's disease, ¹²³I-2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (¹²³I-FP-CIT) SPECT detects striatal dopamine dysfunction resulting from nigral pathology whereas transcranial sonography (TCS) shows increased substantia nigra echogenic size, even before parkinsonism is clinically evident. We postulated that these neuroimaging changes could occur in a proportion of IRBD individuals who might then be at increased risk for development of a neurodegenerative disorder associated with substantia nigra dysfunction. In our prospective study, we identified patients with IRBD from individuals referred to our sleep disorders centre in Barcelona, Spain. At baseline, we assessed dopamine transporter [corrected] uptake by use of ¹²³I-FP-CIT SPECT, and estimated echogenicity of the substantia nigra by use of TCS. After a follow-up of 2·5 years, participants were clinically assessed to establish whether they had developed neurodegenerative syndromes. Data were compared with those of matched healthy controls. 43 individuals with IRBD agreed to participate in the study. We found reduced ¹²³I-FP-CIT binding in the striatum (p=0·045) in 17 (40%) of 43 participants compared with 18 controls, and substantia nigra hyperechogenicity in 14 (36%) of 39 participants with IRBD, compared with 16 (11%) of 149 controls (p=0·0002). Tracer uptake reduction was more pronounced in the putamen than it was in the caudate nucleus. 27 (63%) participants had reduced ¹²³I-FP-CIT binding or substantia nigra hyperechogenicity at baseline. Eight (30%) of these participants developed a neurodegenerative disorder (five Parkinson's disease, two dementia with Lewy bodies, and one multiple system atrophy). Individuals with normal neuroimaging results remained disease-free. Sensitivity of combined ¹²³I-FP-CIT SPECT and TCS to predict conversion to synucleinopathy after 2·5 years was 100% and specificity was 55%. In patients with IRBD, ¹²³I-FP-CIT SPECT and TCS can detect subclinical changes much the same as those typically seen in patients with early Parkinson's disease. Decreased striatal ¹²³I-FP-CIT binding and substantia nigra hyperechogenicity might be useful markers to identify individuals at increased risk for development of synucleinopathies. None.


Embracing National Patient Safety Goals, part 1 of 2.
Take an in-depth look at the National Patient Safety Goals to ensure your organization's compliance.


Indoor environmental factors associated with house-dust-mite allergen (Der p 1) levels in south-eastern Australian houses.
Eighty households in the Latrobe Valley, Victoria, Australia, were sampled for house-dust-mite allergen (Der p 1). Allergen levels vary greatly between houses within climate regions. The reasons for this are not well understood. House-dust-mite allergen samples were collected on six occasions between March 1994 and February 1995. All participating households contained at least one child between 7 and 14 years with a total of 148 subjects, 53 of whom were asthmatic. A detailed house survey was performed during every sampling visit, and a dwelling questionnaire was completed. Relative humidity was measured at the time of sample collection. The median bed allergen level was 30 microg/g during the first sampling period. Significantly higher allergen levels were associated with wool bedding and inner-spring mattresses (P < 0.001). As estimated from a multiple linear regression model, up to 70% reduction in bed allergen levels may be achieved by avoiding wool bedding and inner-spring mattresses. Other risk factors for high allergen levels included high indoor relative humidity, presence of substantial visible mould growth, brick cladding, and concrete slab foundation of the house. Avoiding wool bedding and replacing inner-spring mattresses with foam could substantially reduce bed allergen levels.


The entheomycological origin of Egyptian crowns and the esoteric underpinnings of Egyptian religion.
In this paper, I theorize that the Egyptian White and Triple Crowns were originally primordia of the entheogenic Psilocybe (Stropharia) cubensis, which an Egyptian tale known as Cheops and the Magicians allegorically explained grew on barley, and that Osiris was the God of spiritual rebirth because he personified this and other entheogenic mushrooms. I go on to theorize that the plant known commonly as the Eye of Horus, which the Egyptians included in cakes and ales designed to spiritually rebirth the living and the dead, was an entheogenic mushroom cap entirely analogous, if not identical, to Soma. Finally, I explain why so many scholars failed to discern these identities and relationships for so long.


Vasodilator activity of 2-(p-chloro-alpha-hydroxybenzyl)benzimidazole (HBBPC) on femoral vascular bed of the rabbit.
The effects of 2-(p-chloro-alpha-hydroxybenzyl) benzimidazole HCl (HBBPC) have been studied on the femoral peripheral resistance (i.v. route) and only femoral blood flow (local i.a. injection), in comparison with other vasodilators, i.e., sodium nitroprusside, dihydralazine and piribedil. The vasomotor activity of HBBPC, namely, decreased peripheral resistance and increased femoral blood flow, seems interesting because it begins after pressure has returned to normal. This substance is likely to induce a vasoconstriction in other areas (increased femoral blood flow with decreased peripheral resistance without a fall of blood pressure).


Theta rhythm during REM sleep and waking: correlations between power, phase and frequency.
Short segments of hippocampal EEG in the rat were recorded during rapid-eye-movement sleep (REM) and active waking behaviors. Fourier analysis was used to reveal the time-varying changes of theta power, frequency, coherence and phase in stratum radiatum (apical dendritic layer) of CA1 region. In all cases studied during REM sleep or active waking, a significant, positive correlation of radiatum theta phase and peak theta frequency was found. The radiatum phase was found to range from 100 to 170 degrees and increased towards 180 degrees at high (7.8-8.6 c/sec) theta frequency. Electrodes at sites other than stratum radiatum did not show this phase-frequency relation. By selectively averaging across spectra of EEG with the same selected peak theta frequency, it was found that the power at the first or second theta harmonic, the integrated power of fast EEG (30-100 c/sec) and the radiatum theta phase all generally increased with increasing theta frequency. The results indicate that the radiatum theta phase (and frequency) is dynamically varying during normal behaviors. Together with previous findings on the pharmacology of theta phase, the results suggest that both atropine-sensitive and atropine-resistant inputs are present during normal behaviors.


Immunologic and clinical correlates of bronchial challenge responses to Bermuda grass pollen extracts.
We have studied 26 patients with asthma who had positive skin tests for Bermuda grass pollen antigen (BGP) with history, immunologic assays, and bronchial challenge with BGP. In these patients IgE anti-BGP RAST titers were higher in those with positive, 6.8 +/- 4.4% (mean +/- SEM) compared to those with negative bronchial challenges, 2.7 +/- 0.4% (p less than 0.02). Historical data did not predict bronchial challenge response. IgG4 anti-BGP RAST was not different in patients with positive and negative challenges but was markedly increased, 15.3 +/- 11.9%, in patients who had previously had BGP immunotherapy when compared to untreated patients, 3.6 +/- 5.1% (p less than 0.01). IgE anti-Bermuda grass appears to be the major contributor to susceptibility to BGP bronchial challenge. IgG4 anti-Bermuda grass is apparently unrelated to the sensitivity to challenge but appears to be a significant component of the immunologic response to immunotherapy.


Real-time measurement of total nitrogen for agricultural runoff based on multiparameter sensors and intelligent algorithms.
Real-time monitoring of non-point source (NPS) pollution is challenging owing to the minute-scale change in runoff flow and concentration under rainfall condition. In this study, we proposed a real-time measurement method for total nitrogen (TN) by combining the timeliness of sensor detection and the accuracy of intelligent algorithms, based on the physical and chemical relationships between TN and sensor-measured indexes. Extra tree regression was selected as the TN inversion algorithm, which has high precision, high computational efficiency, and better ability in over-fitting control. The results show that: (1) the real-time inversion algorithm of TN can achieve the monitoring frequency at the minute scale (<5 min); (2) the method performs well (R2>0.9) when the training and testing datasets are from similar environmental backgrounds (fields or ditches); (3) in the case of partial variable missing, this method can still realize TN inversion, and the prediction accuracy is acceptable (R2>0.7) under the number of missing variables (n) ≤ 2, which makes up for the flaws of missing or abnormal data caused by sensor malfunctions. Overall, the proposed real-time measurement method of TN has stable data acquisition, high precision, and high monitoring frequency. In addition, the method is not limited by cloudy, rainy, or nighttime conditions. Compared with methods such as laboratory test, remote sensing inversion, and water quality automatic monitoring station, our method has obvious advantages in runoff monitoring of NPS pollution, which mainly occurs in small and micro water bodies. The new real-time measurement of TN for runoff may provide important technological support for pre-warning and emergency control of NPS pollution.


Phenotypic and genotypic characterization of virulence markers and antifungal susceptibility of oral Candida species from diabetic and non-diabetic hemodialysis patients.
Patients with chronic kidney disease undergoing hemodialysis are often colonized by Candida species with high possibility of fungal infections. The purposes of this study were to determine the prevalence of Candida species, evaluate antifungal susceptibility profile, biofilm formation, proteinase and phospholipase activities, and the frequency of virulence genes in the Candida species isolated from the oral mucosa of hemodialysis diabetic (DM) and non-diabetic (non-DM) patients. This study identified several species of Candida isolated from 69 DM and 58 non-DM patients on hemodialysis using phenotypic methods and PCR-RFLP technique. The identification of C. albicans and C. glabrata complex was performed by HWP1 gene and four oligonucleotides (UNI-5.8S, GLA-f, BRA-f, and NIV-f), respectively. Antifungal susceptibility to amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin was assessed according to CLSI M27-A3/S4. The biomass, metabolic activity of biofilm, proteinase (Prz), phospholipase (Pz), and molecular study for virulence genes were assessed using crystal violet, XTT assay, agar-based hydrolytic enzyme, and PCR technique, respectively. Candida prevalence was 44.9% with 47.8% and 41.4% among DM and non-DM patients, respectively (P = .045). The species identified were C. albicans (49.5%), C. glabrata (16.5%), C. tropicalis (12%), C. kefyr (8.8%), C. parapsilosis (6.6%), C. dubliniensis (3.3%), and C. lusitaniae (3.3%). The antifungal susceptibility profile showed that all Candida isolates were sensitive to amphotericin B, itraconazole, voriconazole, and caspofungin whereas fluconazole resistance was observed in 6.3% (MIC ≥ 64 μg/mL) of C. albicans and 6.6% of C. glabrata (MIC ≥ 64 μg/mL). The susceptible- dose-dependent rate was found in 10.5% of C. albicans. The Prz values of C. albicans ranged from 0.37 to 0.66 for the DM and 0.44-0.73 for the non-DM group (P < 0.05). The non-albicans Candida (NAC) species produced higher degree of biomass and metabolic activity compared to C. albicans (P < 0.05). Furthermore, significant (p < 0.05) correlations were detected between the biofilm formation with Prz values and fluconazole MICs. The most detected virulence factors were ALS3 and Sap5. These results showed the importance of prevalence of NAC species in hemodialysis patients. Investigating antifungal susceptibility profile made a better understanding of the role of virulence markers in the pathogenesis of Candida strains.


Validation and clinical application of the german version of the palliative care outcome scale.
The Palliative Care Outcome Scale (POS) is a multidimensional instrument covering physical, psychosocial, spiritual, organizational, and practical concerns. This study validated the German version of the POS and used the tool in different palliative care settings in Germany and Austria. Patients and staff were asked to complete the POS three times and evaluate the questionnaire and the translation afterwards. One hundred eighteen patients (44 male, 74 female, mean age 63 years, all suffering from advanced cancer) completed the POS one time, 55 patients two times, and 36 patients three times. Spearman's rho was highly significant for pain, other symptoms, anxiety, and life worthwhile in the first two assessments. The third assessment showed significant correlations for pain, other symptoms, anxiety, and family anxiety. Seventy-seven of 87 patients answered questions regarding the scale and the translation. All questions other than "Over the past 3 days, have you felt good about yourself?" were understandable for patients. Almost half of the staff was undecided whether the tool was reflecting the patients' condition. In contrast, the majority of patients liked it. Thus, the German version of the POS is well accepted by patients and staff and appears to be valid, although there are some areas where the scale would benefit from expansion to more closely capture staff and patient concerns.


Fluid-fluid demixing transitions in colloid-polyelectrolyte star mixtures.
We derive effective interaction potentials between hard, spherical colloidal particles and star-branched polyelectrolytes of various functionalities f and smaller size than the colloids. The effective interactions are based on a Derjaguin-like approximation, which is based on previously derived potentials acting between polyelectrolyte stars and planar walls. On the basis of these interactions we subsequently calculate the demixing binodals of the binary colloid-polyelectrolyte star mixture, employing standard tools from liquid-state theory. We find that the mixture is indeed unstable at moderately high overall concentrations. The system becomes more unstable with respect to demixing as the star functionality and the size ratio grow.


Lysine 271 but not lysine 210 of XRCC4 is required for the nuclear localization of XRCC4 and DNA ligase IV.
XRCC4 and DNA Ligase IV (LIG4) cooperate to join two DNA ends at the final step of DNA double-strand break (DSB) repair through non-homologous end-joining (NHEJ). However, it is not fully understood how these proteins are localized to the nucleus. Here we created XRCC4(K271R) mutant, as Lys271 lies within the putative nuclear localization signal (NLS), and XRCC4(K210R) mutant, as Lys210 was reported to undergo SUMOylation, implicated in the nuclear localization of XRCC4. Wild-type and mutated XRCC4 with EGFP tag were introduced into HeLa cell, in which endogenous XRCC4 had been knocked down using siRNA directed to 3'-untranslated region, and tested for the nuclear localization function by fluorescence microscopy. XRCC4(K271R) was defective in the nuclear localization of itself and LIG4, whereas XRCC4(K210R) was competent for the nuclear localization with LIG4. To examine DSB repair function, wild-type and mutated XRCC4 were introduced into XRCC4-deficient M10. M10-XRCC4(K271R), but not M10-XRCC4(K210R), showed significantly reduced surviving fraction after 2 Gy γ-ray irradiation as compared to M10-XRCC4(WT). The number of γ-H2AX foci remaining 2 h after 2 Gy γ-ray irradiation was significantly greater in M10-XRCC4(K271R) than in M10-XRCC4(WT), whereas it was only marginally increased in M10-XRCC4(K210R) as compared to M10-XRCC4(WT). The present results collectively indicated that Lys271, but not Lys210, of XRCC4 is required for the nuclear localization of XRCC4 and LIG4 and that the nuclear localizing ability is essential for DSB repair function of XRCC4.


The role of the vascular phase in solid tumor growth: a historical review.
Angiogenesis is a biological process by which new capillaries are formed from pre-existing vessels. It occurs in both physiological conditions such as embryo development, cyclically in the female genital system and during wound repair, and pathological conditions, such as arthritis, diabetic retinopathy and tumors. In solid tumor growth, a specific critical turning point is the transition from the avascular to the vascular phase. Having developed an intrinsic vascular network, the neoplastic mass is able to grow indefinitely (unlike all the other forms, tumor angiogenesis is not limited in time) both in situ and at distant sites (metastasis) in so far as an intrinsic vascular network enables its cells to enter the vascular bed and colonize other organs. Tumor angiogenesis depends mainly on the release by neoplastic cells of growth factors specific for endothelial cells and able to stimulate growth of the host's blood vessels. This review describes its history as traced by the main contributions to the international medical literature and their contents. The specific new paradigm discussed here has been gaining general approval and considerable confirmation, thanks to its possible applications, as recently highlighted by the introduction of anti-angiogenic substances in adjuvant tumor management.


The role of the liver in clearance of glycoproteins from the general circulation, with special reference to intestinal alkaline phosphatase.
Glycoproteins represent a wide variety of macromolecules with important physiological functions. Characteristic variations in carbohydrate composition and plasma concentration of these proteins may occur during pathological conditions. Steady-state plasma concentrations are determined by release from normal or diseased tissues and simultaneous clearance from the general circulation. The liver occupies a central position in the production but also clearance and catabolism of such glycoproteins. A number of specialized receptor-mediated transport processes for different types of glycoproteins in this organ is reviewed. Membrane recognition is generally followed by absorptive endocytosis and vesicle transport to lysosomes, Golgi system and/or bile canaliculis. The charge of the protein, the nature of the terminal sugar residue or complex formation with other glycoproteins may determine the extent of uptake in the various cell types of the liver. By means of these transport processes the liver is able to remove potentially dangerous macromolecules such as denatured proteins, aggressive enzymes and immunocomplexes from the general circulation. Drugs can bind to some of these proteins or may interact with the hepatic transport or catabolism processes. Special attention is paid to the hepatic clearance of asialoglycoproteins with terminal galactose groups. Intestinal alkaline phosphatase is used as a model compound to characterize the pharmacokinetic profiles of hepatic uptake and biliary excretion in the rat in vivo and isolated perfused rat livers. Histochemical and electron-microscopic studies demonstrated a galactose-specific, receptor-mediated endocytotic process, mainly but not exclusively localized in centrolobular hepatocytes. Drug interactions with these processes will be the subject of further investigations.


Draft Genome Sequence of Methylobacterium radiotolerans Strain MAMP 4754, a Bacterial Endophyte Isolated from Combretum erythrophyllum in South Africa.
We announce here the draft genome sequence of Methylobacterium radiotolerans strain MAMP 4754, isolated from the roots of the medicinal plant Combretum erythrophyllumM. radiotolerans has a genome size of 7,389,282 bp with 7,166 genes and a G+C content of 70.5%.


Clinical characteristics of diabetic ketoacidosis in newly diagnosed adult patients.
A retrospective review was conducted of medical records of newly diagnosed diabetes in adults who presented with DKA between 2003 and 2007. The majority of DKA in Thailand could not be classified as classical type 1 diabetes. Some newly diagnosed people presenting with DKA could be safely withdrawn from insulin treatment.


Knemometry, a new tool for the investigation of growth. A review.
Cross-sectional and longitudinal studies of human growth have revealed almost every detail of the typical human growth pattern. Yet, the description of this pattern is still limited to the traditional vocabulary of "growth rates", i.e. height or length differences divided by certain time intervals such as months or years. Almost no information is yet available on finer details of this pattern. This review concerns the existing experimental and clinical data collected by a novel and non-invasive technique of accurate lower leg length measurement named "knemometry" that has been used for the study of short-term growth. This technique estimates the distance between heel and knee of the sitting child with an accuracy (technical error) of 0.09-0.16 mm. Several authors have presented evidence that lower leg growth is non-linear. There is not only a marked day-to-day variation of the lower leg length which far exceeds the error of the measurement itself, but there is also a characteristic up-and-down pattern of lower leg growth consisting of sharp growth spurts ("mini-growth-spurts") alternating with periods of decreased growth velocity every 30-55 days in 45 out of 73 healthy children. This pattern can be visualized by the calculation of "mean daily lower leg growth velocities", an approach that gives information on the kinetic properties of the growth process. In spite of much initial criticism, knemometry has opened a fascinating new dimension of the physiology of human growth and provided finer details of growth than hitherto obtainable by conventional techniques of growth measurement.


Immunotoxicity of repeated low level exposure to T-2 toxin, a trichothecene mycotoxin, in CD-1 mice.
Male CD-1 mice were gavaged with T-2 toxin (0.0-5.0 mg/kg body weight) every third day. Body weight gain was depressed by exposure to 2.5 mg/kg, or greater, T-2 toxin; this was not associated with decreased food intake. The weights of the liver, kidney, spleen, and thymus were affected by two weeks exposure to T-2 toxin. However, a persistent effect after four weeks was observed only for the thymus. Peripheral leucocyte counts were elevated in the highest dose groups after two and four weeks. Thymidine uptake by cells not simultaneously exposed to mitogen was increased in splenic cell cultures of mice exposed to 2.5 mg/kg T-2 toxin for two or four weeks. Phytohemagglutinin stimulation of splenic lymphocytes following two weeks of exposure was depressed in the 2.5 mg/kg dose group; this phenomenon was not observed after four weeks exposure. Response to pokeweed mitogen increased after four weeks of exposure to 2.5 mg/kg T-2 toxin. A delayed-type hypersensitivity response decreased following two weeks exposure to levels greater than 0.02 mg/kg. Production of I g M class antibodies by splenic lymphocytes, evaluated by a hemolytic plaque response to sheep erythrocytes, was depressed in the 2.5 mg/kg dose group after two weeks exposure to T-2 toxin. The sensitivity and specificity of T-2 toxin immunotoxicity was indicated by the various parameters evaluated.


Distinct Stress-Dependent Signatures of Cellular and Extracellular tRNA-Derived Small RNAs.
The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may identify novel biomarkers and key signaling pathways for different diseases. Emerging evidence shows that transfer RNA-derived small RNAs (tDRs) play pivotal roles in stress responses. However, RNA modifications present on tDRs are barriers to accurately quantifying tDRs using traditional small RNA sequencing. Here, AlkB-facilitated methylation sequencing is used to generate a comprehensive landscape of cellular and extracellular tDR abundances in various cell types during different stress responses. Extracellular tDRs are found to have distinct fragmentation signatures from intracellular tDRs and these tDR signatures are better indicators of different stress responses than miRNAs. These distinct extracellular tDR fragmentation patterns and signatures are also observed in plasma from patients on cardiopulmonary bypass. It is additionally demonstrated that angiogenin and RNASE1 are themselves regulated by stressors and contribute to the stress-modulated abundance of sub-populations of cellular and extracellular tDRs. Finally, a sub-population of extracellular tDRs is identified for which AGO2 appears to be required for their expression. Together, these findings provide a detailed profile of stress-responsive tDRs and provide insight about tDR biogenesis and stability in response to cellular stressors.


Metadata and Reuse: Antidotes to Information Entropy.
Entropy is the natural tendency for decline toward disorder over time. Information entropy is the decline in data, information, and understanding that occurs after data are used and results are published. As time passes, the information slowly fades into obscurity. Data discovery is not enough to slow this process. High-quality metadata that support understanding and reuse and cross domains are a critical antidote to information entropy, particularly as it supports reuse of the data-adding to community knowledge and wisdom. Ensuring the creation and preservation of these metadata is a responsibility shared across the entire data life cycle from creation through analysis and publication to archiving and reuse. Repositories can play an important role in this process by augmenting metadata through time with persistent identifiers and connections they facilitate. Data providers need to work with repositories to encourage metadata evolution as new capabilities and connections emerge.


LC-ESI-MS/MS quantification of 4β-hydroxycholesterol and cholesterol in plasma samples of limited volume.
A liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) assay was developed and qualified for analyzing 4β-hydroxycholesterol and cholesterol in 5 μl of human and mouse plasma. Stable isotope-labeled d7-analogs of both analytes were used as internal standards and 4.2% (w/v) human serum albumin in phosphate-buffered saline was used as the surrogate matrix for preparation of calibration curves and QCs. The assay is capable of quantification of 4β-hydroxycholesterol and cholesterol from 5 to 500 ng/ml and 50 to 2000 μg/ml, respectively, with acceptable accuracy and precision following evaluation of recovery of analytes, autosampler stability and potential contribution of chemical oxidation to the formation of 4β-hydroxycholesterol. The final reconstituted solution was diluted for quantification of cholesterol typically present at 1000 fold higher concentration than 4β-hydroxycholesterol in the same samples used for 4β-hydroxycholesterol quantification. The successful quantification using a low plasma volume was achieved by quantification of total forms (free and conjugated) of both analytes after alkaline hydrolysis, followed by derivatization to form electrospray ionization-sensitive picolinyl esters, which upon collision-induced dissociation gave high mass precursor-product ion pair for selective detection by multiple reaction monitoring. In addition, chromatographic separation using a 16-min reversed phase gradient elution on a 1.9 μm particle size, C18 column, overcame interference from other isobaric plasma oxysterols during detection by multiple-reaction monitoring. This assay was compared to an orthogonal enzymatic assay for cholesterol and all samples, but one, provided values that were within 10% of each other. In addition, this assay passed the incurred sample tests for both analytes in human and mouse plasma samples according to reported acceptance criteria for incurred sample reanalysis. The quantification of both analytes permitted the determination of 4β-hydroxycholesterol compared to its ratio to cholesterol as an endogenous biomarker for CYP3A4/5 activity. The LC-ESI-MS/MS assay was also successfully applied to quantification of 4β-hydroxycholesterol and cholesterol in plasma samples from untreated human and mice including FRG™ KO C57Bl/6 chimeric mice with humanized livers. The preliminary data indicated that the plasma 4β-hydroxycholesterol concentrations or their ratio to cholesterol from mice including chimeric mice were higher than those from human.