Human dendritic cells express the IL-18R and are chemoattracted to IL-18.
IL-18 is secreted by a variety of cells such as epithelial cells, macrophages, and dendritic cells (DC), in particular, in areas of chronic inflammation. The effects of IL-18 are complex and not fully understood thus far. We sought to explore human DC as a new target for IL-18, since IL-18R expression has been described on myeloid cells such as macrophages and DC are likely to get in contact with IL-18 at sites of inflammatory reactions. We demonstrate the expression of the IL-18R on human DC in peripheral blood and epidermis, as well as monocyte-derived dendritic cells (MoDC). On MoDC, IL-18R expression is up-regulated by IFN-gamma. IL-18 strongly up-regulated CD54 on MoDC, whereas the effect on MHC class II, CD83, and CD86 was only moderate and the expression of CD40 and CD80 was not affected. MoDC primed with IL-18 did not increase their capacity to stimulate the proliferation or IFN-gamma production of autologous T cells. However, IL-18 had a direct migratory effect on MoDC as indicated by induction of filamentous actin polymerization and migration in Boyden chamber experiments. In epidermal DC, IL-18 was also able to induce filamentous actin polymerization. Therefore, IL-18 might represent a novel mechanism to recruit DC to areas of inflammation, in particular under Th1 cytokine conditions where IFN-gamma is increased such as psoriasis or inflammatory bowel diseases.


What RNAi screens in model organisms revealed about microbicidal response in mammals?
The strategies evolved by pathogens to infect hosts and the mechanisms used by the host to eliminate intruders are highly complex. Because several biological pathways and processes are conserved across model organisms, these organisms have been used for many years to elucidate and understand the mechanisms of the host-pathogen relationship and particularly to unravel the molecular processes enacted by the host to kill pathogens. The emergence of RNA interference (RNAi) and the ability to apply it toward studies in model organisms have allowed a breakthrough in the elucidation of host-pathogen interactions. The aim of this mini-review is to highlight and describe recent breakthroughs in the field of host-pathogen interactions using RNAi screens of model organisms. We will focus specifically on the model organisms Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio. Moreover, a recent study examining the immune system of planarian will be discussed.


Transgene expression in regenerated roots.
INTRODUCTIONThis procedure, which uses a root transformation protocol, provides a rapid method for assessing gene expression in Arabidopsis roots. It is useful for testing promoter:reporter gene constructs, for expressing genes, the overexpression of which is lethal in whole plants, and for transforming the roots of plants that are recalcitrant to conventional transformation techniques. The protocol has been used successfully with Ws, No-0, and RLD ecotypes.


Defining the molecular basis of amyloid inhibitors: human islet amyloid polypeptide-insulin interactions.
Human islet amyloid polypeptide (hIAPP or Amylin) is a 37 residue hormone that is cosecreted with insulin from the pancreatic islets. The aggregation of hIAPP plays a role in the progression of type 2 diabetes and contributes to the failure of islet cell grafts. Despite considerable effort, little is known about the mode of action of IAPP amyloid inhibitors, and this has limited rational drug design. Insulin is one of the most potent inhibitors of hIAPP fibril formation, but its inhibition mechanism is not understood. In this study, the aggregation of mixtures of hIAPP with insulin, as well as with the separate A and B chains of insulin, were characterized using ion mobility spectrometry-based mass spectrometry and atomic force microscopy. Insulin and the insulin B chain target the hIAPP monomer in its compact isoform and shift the equilibrium away from its extended isoform, an aggregation-prone conformation, and thus inhibit hIAPP from forming β-sheets and subsequently amyloid fibrils. All-atom molecular modeling supports these conclusions.


Virtual trial to evaluate the robustness of cementless femoral stems to patient and surgical variation.
Primary stability is essential for the success of cementless femoral stems. In this study, patient specific finite element (FE) models were used to assess changes in primary stability due to variability in patient anatomy, bone properties and stem alignment for two commonly used cementless femoral stems, Corail® and Summit® (DePuy Synthes, Warsaw, USA). Computed-tomography images of the femur were obtained for 8 males and 8 females. An automated algorithm was used to determine the stem position and size which minimized the endo-cortical space, and then span the plausible surgical envelope of implant positions constrained by the endo-cortical boundary. A total of 1952 models were generated and ran, each with a unique alignment scenario. Peak hip contact and muscle forces for stair climbing were scaled to the donor's body weight and applied to the model. The primary stability was assessed by comparing the implant micromotion and peri-prosthetic strains to thresholds (150 μm and 7000 µε, respectively) above which fibrous tissue differentiation and bone damage are expected to prevail. Despite the wide range of implant positions included, FE prediction were mostly below the thresholds (medians: Corail®: 20-74 µm and 1150-2884 µε, Summit®: 25-111 µm and 860-3010 µε), but sensitivity of micromotion and interfacial strains varied across femora, with the majority being sensitive (p < 0.0029) to average bone mineral density, cranio-caudal angle, post-implantation anteversion angle and lateral offset of the femur. The results confirm the relationship between implant position and primary stability was highly dependent on the patient and the stem design used.


Probable interaction between warfarin and marijuana smoking.
To report a probable interaction between warfarin and marijuana smoking, resulting in increased international normalized ratio (INR) values and bleeding complications. A 56-year-old white male had been receiving chronic warfarin therapy for 11 years after mechanical heart valve replacement. He was admitted to the hospital with a diagnosis of upper gastrointestinal bleeding. Upon admission, his INR value was supratherapeutic at 10.41, and his hemoglobin level was 6.6 g/dL. He received 4 units of fresh frozen plasma and one 10-mg dose of oral vitamin K; his INR was 1.8 the next day. He was discharged 7 days after admission. Fifteen days after hospital discharge, he was readmitted with a constant nosebleed and increased bruising. His INR value was 11.55. After treatment, he was discharged with an INR value of 1.14. The patient smoked marijuana more frequently throughout the period of these 2 hospitalizations due to his depression. He was counseled by the pharmacist on the potential interaction of warfarin and marijuana. The patient decided to stop smoking marijuana after the third counseling session. During the 9 months that he did not smoke marijuana, his INR values ranged from 1.08 to 4.40 with no significant bleeding complications. Marijuana may increase warfarin anticoagulant effect by inhibiting its metabolism, and to a lesser extent, displacing warfarin from protein-binding sites. Other causes (eg, nonadherence) of the patient's increased INR were ruled out. Using the Horn Drug Interaction Probability Scale, our patient's warfarinmarijuana interaction appeared to be probable. To our knowledge, there have been no other reported cases of warfarin-marijuana interaction. While more clinical reports would be useful to confirm this interaction, clinicians should be aware of its probability so as to manage patients appropriately.


Focal Adhesion Kinase Expression in Ameloblastoma: A Preliminary Observational Study.
Focal Adhesion Kinase (FAK) is a membrane-associated molecule, which plays a major role in tumourigenesis by promoting cell survival, proliferation, migration, and invasion. Hence, FAK is a well known molecule that has been targeted therapeutically for the treatment of various malignancies. Ameloblastoma (AB) is a locally invasive, destructive and recurrent benign odontogenic lesion. Based on these properties, we have hypothesized that odontogenic epithelium of AB could show increased expression of FAK. To study the expression of FAK in odontogenic epithelium of AB using immunohistochemistry. Thirty four paraffin embedded AB and 17 Dental Follicle (DF) tissues were retrieved from archives. Immunohistochemical staining was performed using FAK antibody on 5 μm thick formalin fixed paraffin embedded sections. The expression of FAK was studied in ameloblast like cells and stellate reticulum-like cells and was graded as negative, weak and strong. The data was analysed using chi-square test and Fisher's-exact test. In AB, both ameloblast like and stellate reticulum like cells showed positive expression of FAK in the cytoplasm in all the cases (34). The epithelial islands from all the DFs (17) were negative for FAK expression. The difference in the expression of FAK in ameloblast like and stellate reticulum like cells was statistically significant (p<0.0001). Statistically significant difference was observed in the expression of FAK in stellate reticulum like cells of AB and odontogenic epithelial islands of DF (p = 0.0017). All the AB cases showed strong expression of FAK in ameloblast like cells and negative expression was seen in all the cases of DF. FAK was strongly expressed in AB as compared to epithelial islands of DF. FAK could be responsible for the neoplastic nature of AB and possibly play a role in tumour invasiveness.


Stabilized supralinear network can give rise to bistable, oscillatory, and persistent activity.
A hallmark of cortical circuits is their versatility. They can perform multiple fundamental computations such as normalization, memory storage, and rhythm generation. Yet it is far from clear how such versatility can be achieved in a single circuit, given that specialized models are often needed to replicate each computation. Here, we show that the stabilized supralinear network (SSN) model, which was originally proposed for sensory integration phenomena such as contrast invariance, normalization, and surround suppression, can give rise to dynamic cortical features of working memory, persistent activity, and rhythm generation. We study the SSN model analytically and uncover regimes where it can provide a substrate for working memory by supporting two stable steady states. Furthermore, we prove that the SSN model can sustain finite firing rates following input withdrawal and present an exact connectivity condition for such persistent activity. In addition, we show that the SSN model can undergo a supercritical Hopf bifurcation and generate global oscillations. Based on the SSN model, we outline the synaptic and neuronal mechanisms underlying computational versatility of cortical circuits. Our work shows that the SSN is an exactly solvable nonlinear recurrent neural network model that could pave the way for a unified theory of cortical function.


Growth of Arabidopsis thaliana seedlings under water deficit studied by control of water potential in nutrient-agar media.
We have characterized the growth responses of Arabidopsis thaliana seedlings to water deficit. To manipulate the water potential, we developed a method whereby the nutrient-agar medium could be supplemented with polyethylene glycol (PEG 8000); PEG was introduced into gelled media by diffusion, which produced media with water potential as low as -1.6 MPa. For dark-grown plants, hypocotyl growth had a hyperbolic dependence on water potential, and was virtually stopped by -1 MPa. In contrast, primary root elongation was stimulated by moderate deficit and even at -1.6 MPa was not significantly less than the control. That these results did not depend on a direct effect of PEG was attested by obtaining indistinguishable results when a dialysis membrane impermeable to PEG was placed between the medium and the seedlings. For light-grown seedlings, moderate deficit also stimulated primary root elongation and severe deficit reduced elongation only partially. These changes in elongation were paralleled by changes in root system dry weight. At moderate deficit, lateral root elongation and initiation were unaffected and at higher stress levels both were inhibited. Primary root diameter increased steadily with time in well-watered controls and under water deficit increased transiently before stabilizing at a diameter that was inversely proportional to the deficit. Along with stimulated primary root elongation, moderate water deficit also stimulated the rate of cell production. Thus, A. thaliana responds to water deficit vigorously, which enhances its use as a model to uncover mechanisms underlying plant responses to water deficit.


High-speed device synchronization in optical microscopy with an open-source hardware control platform.
Azimuthal beam scanning eliminates the uneven excitation field arising from laser interference in through-objective total internal reflection fluorescence (TIRF) microscopy. The same principle can be applied to scanning angle interference microscopy (SAIM), where precision control of the scanned laser beam presents unique technical challenges for the builders of custom azimuthal scanning microscopes. Accurate synchronization between the instrument computer, beam scanning system and excitation source is required to collect high quality data and minimize sample damage in SAIM acquisitions. Drawing inspiration from open-source prototyping systems, like the Arduino microcontroller boards, we developed a new instrument control platform to be affordable, easily programmed, and broadly useful, but with integrated, precision analog circuitry and optimized firmware routines tailored to advanced microscopy. We show how the integration of waveform generation, multiplexed analog outputs, and native hardware triggers into a single central hub provides a versatile platform for performing fast circle-scanning acquisitions, including azimuthal scanning SAIM and multiangle TIRF. We also demonstrate how the low communication latency of our hardware platform can reduce image intensity and reconstruction artifacts arising from synchronization errors produced by software control. Our complete platform, including hardware design, firmware, API, and software, is available online for community-based development and collaboration.


The effects of ACTH, prednisolone and Escherichia coli endotoxin on some clinical haematological and blood biochemical parameters in dwarf goats.
ACTH (microgram kg-1 i.v.) and prednisolone (1 microgram-1 i.v.) caused a moderate but statistically significant inhibition of rumen contractions, whereas no effects on heart rate and body temperature were observed. Both hormones induced hyperglycaemia and leucocytosis, characterised by moderate lymphopenia and a profound increase in the number of circulating neutrophils. A significant decrease in plasma iron and increase in plasma zinc concentrations were observed. After 3 daily i.m. injections of ACTH (10 micrograms-1 day-1) decreases were seen in both serum Alkaline phosphatase (ALP) activity and plasma trace metal concentrations; heart rate was significantly higher. Intraveneous injection of E. coli endotoxin (0.1 microgram kg-1) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophilic leucocytosis, hypoferraemia, hypozincaemia, hypoglycaemia and a decline in serum ALP activity. ACTH, given i.m. for 3 days, reduced the febrile responses to E. coli endotoxin, modified the changes in heart rate, intensified the inhibition of rumen contractions, and induced a more marked decrease in the number of circulating neutrophils. ACTH pretreatment did not affect the endotoxin-induced decrease in blood glucose concentrations nor the drop in plasma zinc and iron values. These results suggest that glucocorticosteroids are not primarily involved in the fall in plasma iron and zinc concentrations during E. coli endotoxin-induced fever, the effects of endotoxin released glucocorticosteroids on white blood cells and blood glucose are masked by some other effect(s) of endotoxin, and in dwarf goats, ACTH has antipyretic properties without influencing normal body temperature. This effect is probably not dependent on adrenal cortical activity.


Learning with hierarchical-deep models.
We introduce HD (or "Hierarchical-Deep") models, a new compositional learning architecture that integrates deep learning models with structured hierarchical Bayesian (HB) models. Specifically, we show how we can learn a hierarchical Dirichlet process (HDP) prior over the activities of the top-level features in a deep Boltzmann machine (DBM). This compound HDP-DBM model learns to learn novel concepts from very few training example by learning low-level generic features, high-level features that capture correlations among low-level features, and a category hierarchy for sharing priors over the high-level features that are typical of different kinds of concepts. We present efficient learning and inference algorithms for the HDP-DBM model and show that it is able to learn new concepts from very few examples on CIFAR-100 object recognition, handwritten character recognition, and human motion capture datasets.


Diagnosing peripheral neuropathy in South-East Asia: A focus on diabetic neuropathy.
Burning and stabbing pain in the feet and lower limbs can have a significant impact on the activities of daily living, including walking, climbing stairs and sleeping. Peripheral neuropathy in particular is often misdiagnosed or underdiagnosed because of a lack of awareness amongst both patients and physicians. Furthermore, crude screening tools, such as the 10-g monofilament, only detect advanced neuropathy and a normal test will lead to false reassurance of those with small fiber mediated painful neuropathy. The underestimation of peripheral neuropathy is highly prevalent in the South-East Asia region due to a lack of consensus guidance on routine screening and diagnostic pathways. Although neuropathy as a result of diabetes is the most common cause in the region, other causes due to infections (human immunodeficiency virus, hepatitis B or C virus), chronic inflammatory demyelinating polyneuropathy, drug-induced neuropathy (cancer chemotherapy, antiretrovirals and antituberculous drugs) and vitamin deficiencies (vitamin B1 , B6 , B12 , D) should be actively excluded.


Oro-facial muscles: internal structure, function and ageing.
Structure and function are reviewed in the masticatory muscles and in the muscles of the lower face and tongue. The enormous strength of jaw closure is in large part due to the pinnated arrangement of the muscle fibres in the masseter. This muscle, like other masticatory muscles, is unusual in that the cell bodies of the muscle spindle afferents lie in the brain stem rather than in an external ganglion; spindles are absent in the lower facial muscles. Although few data are available, the numbers of motor units in the masticatory muscles, and probably in the lower facial muscles also, appear to be much greater than in limb muscles. The motor units in the facial and tongue muscles are largely composed of histochemical type II ('fast-twitch') fibres, but in the masticatory muscles there are substantial numbers of fibres intermediate between type I ('slow twitch') and type II, and fibre type grouping is present. In comparison with limb muscles, there is little information on ageing changes in oro-facial muscles. The masticatory muscles do, however, show some atrophy and loss of X-ray density, while motor unit twitches are prolonged. Strength is reduced in the tongue and masticatory muscles. It is known that limb muscle properties are largely governed by their innervation, both through the pattern and amount of impulse activity, and the delivery of trophic messengers; the situation for oro-facial muscles is unclear. The structural and functional differences between the two types of muscle indicate the need for conducting ageing studies on the oro-facial muscles, rather than relying on extrapolations from limb muscles.


Progress in understanding adolescent language disorders.
This prologue introduces a clinical forum on adolescent language disorders, a topic that has long been of interest to school-based speech-language pathologists/therapists. A rationale for the clinical forum is provided, and the content is contrasted with a previous forum on the same topic that was published nearly 20 years ago. Implications and directions for future research and practice in adolescent language disorders are discussed. Considerable progress has occurred in our understanding of the nature, assessment, and treatment of language and communication disorders in adolescents and young adults. Yet we continue to need to build the evidence base on the most effective and efficient ways of enhancing the spoken and written language skills of young people with language and communication disorders in academic, social, emotional, and vocational domains.


Effect of training and vitamin E administration on rat liver oxidative metabolism.
We studied vitamin E effects on metabolic changes and oxidative damage elicited by swim training in rat liver. Training reduced mitochondrial aerobic capacity but increased liver content of mitochondrial proteins, so that tissue aerobic capacity was not different in trained and sedentary animals. Vitamin E supplementation prevented the training-induced mitochondrial changes. Training and vitamin E effects were consistent with the changes in tissue content of factors involved in mitochondrial biogenesis (peroxisomal proliferator-activated receptor-γ coactivator and nuclear respiratory factors 1 and 2). Tissue and mitochondrial oxidative damage was reduced by training decreasing the rate of mitochondrial reactive oxygen species (ROS) production and enhancing glutathione levels and glutathione peroxidase and glutathione reductase activities. The effects of vitamin E were different when it was administered to sedentary or trained rats. In the former, vitamin E reduced liver preparations oxidative damage decreasing ROS production rate and increasing GSH content without any effect on antioxidant enzyme activities. In the latter, vitamin E did not modify ROS production and oxidative damage but decreased antioxidant levels. This decrease was likely responsible for the enhanced susceptibility to in vitro oxidative attack of the hepatic tissue from trained rats following vitamin E supplementation. These results indicate that vitamin E integration, which can be healthy for animals subjected to acute exercise, is not advisable during training because it prevents or reduces the favourable effects of the physical activity. They also support the idea that the stimulus for training-induced adaptive responses can derive from the increased ROS production that accompanies the single sessions of the training program.


Control of dual isoforms of Ca2+ release channels in muscle.
Here we compare excitation-contraction coupling in single muscle cells of frogs and rats. Because amphibians have isoform 3 (or 3) of the ryanodine receptor/Ca2+ release channel, in addition to 1 (alpha), which is also present in the mammal, any extra feature present in the frog may in principle be attributed to isoform 3. Ca2+ release under voltage clamp depolarization has a peak and a steady phase in both taxonomic classes, but the peak is more marked in the frog, where the ratio of amplitudes of the two phases is voltage-dependent. This dependence is a hallmark of CICR. Confocal imaging identified Ca2+ sparks in the frog, but not in the voltage-clamped rat cells. Because Ca2+ sparks involve CICR both observations indicate that the contribution of CICR is minor or null in the mammal. The "couplon" model well accounts for observations in the frog, but assumes a structure that we now know to be valid only for the rat. A revised model is proposed, whereby the isoform 3 channels, located parajunctionally, are activated by CICR and contribute its characteristic global and local features. Several issues regarding the roles of different channels remain open to further study.


Effect of temperature upon carbon dioxide stores in the snake Coluber constrictor and the turtle Chrysemys scripta.
The effect of temperature upon respiratory exchange ratio (R) was measured in snakes (Coluber constrictor) and turtles (Chrysemys scripta). Increasing body temperature produced a transient elevation of R, and lowering body temperature transiently depressed R. These thermal effects resulted from an 'excess' and a 'deficit' CO2 elimination, respectively. Steady-state blood CO2 content (CCO2) in C. constrictor decreased linearly with rising temperature. Plasma bicarbonate concentration, calculated from in vivo arterial PCO2 and pH, followed the same pattern. Also, time courses of blood CCO2 were consistent with the metabolic studies. Less than half of the change in blood CCO2 could be explained by shifts of the in vitro CO2 dissociation curve; the remainder was contributed by other tissues. Blood lactate levels changed little with temperature. Based upon the blood studies, the predicted quantity of CO2 eliminated from the extracellular space when temperature increases is about 29% of the excess CO2 eliminated from the snakes. Thus, CCO2 in other tissues also decreases with rising temperature. It is concluded that reptiles function as open systems with respect to CCO2, which does not agree with alphastat control. Systemic arterial PO2 and PCO2 increased with rising body temperature in C. constrictor. The mechanisms producing these increases are discussed.


Correlations between Ratings and Technical Measurements in Hand-Intensive Work.
An accurate rating of hand activity and force is essential in risk assessment and for the effective prevention of work-related musculoskeletal disorders. However, it is unclear whether the subjective ratings of workers and observers correlate to corresponding objective technical measures of exposure. Fifty-nine workers were video recorded while performing a hand-intensive work task at their workplace. Self-ratings of hand activity level (HAL) and force (Borg CR10) using the Hand Activity Threshold Limit Value® were assessed. Four ergonomist observers, in two pairs, also rated the hand activity and force level for each worker from video recordings. Wrist angular velocity was measured using inertial movement units. Muscle activity in the forearm muscles flexor carpi radialis (FCR) and extensor carpi radialis (ECR) was measured with electromyography root mean square values (RMS) and normalized to maximal voluntary electrical activation (MVE). Kendall's tau-b correlations were statistically significant between self-rated hand activity and wrist angular velocity at the 10th, 50th, and 90th percentiles (0.26, 0.31, and 0.23) and for the ratings of observers (0.32, 0.41, and 0.34). Significant correlations for force measures were found only for observer-ratings in five of eight measures (FCR 50th percentile 0.29, time > 10%MVE 0.43, time > 30%MVE 0.44, time < 5% -0.47) and ECR (time > 30%MVE 0.26). The higher magnitude of correlation for observer-ratings suggests that they may be preferred to the self-ratings of workers. When possible, objective technical measures of wrist angular velocity and muscle activity should be preferred to subjective ratings when assessing risks of work-related musculoskeletal disorders.


MCP-1 in psoriatic patients: effect of biological therapy.
Monocyte chemoattractant protein-1 (MCP-1) is a chemokine locally and systemically augmented in psoriasis. A single nucleotide polymorphism in MCP-1 promoter region -2518A→G is associated with higher gene expression. The aim was to evaluate MCP-1 plasma level in psoriatic patients and to relate any association in plasmatic and cutaneous MCP-1 with clinical improvement due to biological drugs. Blood samples were obtained from: (i) 30 Caucasian patients with psoriasis and 10 controls, for determining MCP-1 plasma concentrations and -2518A→G polymorphism occurrence, (ii) 16 psoriatic patients treated by anti-tumor necrosis factor-α (TNF-α) adalimumab/etanercept or by anti-CD-11 efalizumab, before and after 2 months of treatment. Moreover, biopsies were performed on lesional skin of five patients treated with anti-TNF-α. MCP-1 plasma concentration and cutaneous expression were determined by ELISA and qRT-PCR. MCP-1 plasma level was significantly increased in psoriatic patients. -2518A→G polymorphism was similarly distributed in patients and controls and unrelated to MCP-1 plasma level or to Psoriasis Area and Severity Index. All patients receiving biological drugs showed significant clinical improvement. Anti-TNF-α therapy moderately reduced MCP-1 plasma concentration and robustly decremented MCP-1 expression in lesional skin. MCP-1 should be a potential local inflammatory marker in psoriatic patients to assess disease severity and anti-TNF-α treatment efficacy.


[Surgical treatment of eyeball atrophy with biological implant material alloplant: the structure and time course of morphological and physiological changes].
The time course of changes in the size of the eyeball and in intraocular pressure (IOP) is analyzed in 50 patients with posttraumatic subatrophy of the eyeball subjected to surgical treatment making use of the Alloplant biological materials and followed up for at least 3 years. The methods of dispersion, factor, cluster, and discriminant analysis have been used. The phases of the initial (directly after surgery) and remote changes were distinguished; changes in the size of the eyeball virtually did not depend on changes in IOP. Typological groups (clusters) of dynamic changes in the size of the eyeball and IOP were distinguished.


Genetic modifier screens reveal new components that interact with the Drosophila dystroglycan-dystrophin complex.
The Dystroglycan-Dystrophin (Dg-Dys) complex has a capacity to transmit information from the extracellular matrix to the cytoskeleton inside the cell. It is proposed that this interaction is under tight regulation; however the signaling/regulatory components of Dg-Dys complex remain elusive. Understanding the regulation of the complex is critical since defects in this complex cause muscular dystrophy in humans. To reveal new regulators of the Dg-Dys complex, we used a model organism Drosophila melanogaster and performed genetic interaction screens to identify modifiers of Dg and Dys mutants in Drosophila wing veins. These mutant screens revealed that the Dg-Dys complex interacts with genes involved in muscle function and components of Notch, TGF-beta and EGFR signaling pathways. In addition, components of pathways that are required for cellular and/or axonal migration through cytoskeletal regulation, such as Semaphorin-Plexin, Frazzled-Netrin and Slit-Robo pathways show interactions with Dys and/or Dg. These data suggest that the Dg-Dys complex and the other pathways regulating extracellular information transfer to the cytoskeletal dynamics are more intercalated than previously thought.


Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled trial.
Because cholinergic deficits are prominent in dementia with Lewy bodies (DLB), we investigated the effects of a cholinesterase inhibitor, donepezil, in such patients in a randomized, double-blind, placebo-controlled exploratory phase 2 trial. One-hundred forty patients with DLB, recruited from 48 specialty centers in Japan, were randomly assigned to receive placebo or 3, 5, or 10 mg of donepezil hydrochloride daily for 12 weeks (n = 35, 35, 33, and 37, respectively). Effects on cognitive function were assessed using the Mini-Mental State Examination (MMSE) and several domain-specific neuropsychological tests. Changes in behavior were evaluated using the Neuropsychiatric Inventory, caregiver burden using the Zarit Caregiver Burden Interview, and global function using the Clinician's Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus). Safety measures included the Unified Parkinson's Disease Rating Scale part III. Donepezil at 5 and 10 mg/day was significantly superior to placebo on both the MMSE (5 mg: mean difference, 3.8; 95% confidence interval [CI], 2.3-5.3; p < 0.001; 10 mg: mean difference, 2.4; 95% CI, 0.9-3.9; p = 0.001) and CIBIC-plus (p < 0.001 for each); 3 mg/day was significantly superior to placebo on CIBIC-plus (p < 0.001), but not on the MMSE (p = 0.017). Significant improvements were found also in behavioral measures (p < 0.001) at 5 and 10 mg/day and caregiver burden (p = 0.004) at 10 mg/day. The safety results were consistent with the known profile of donepezil and similar among groups. Donepezil at 5 and 10mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose. Donepezil is safe and well tolerated.


Dynamic changes in network synchrony reveal resting-state functional networks.
Experimental functional magnetic resonance imaging studies have shown that spontaneous brain activity, i.e., in the absence of any external input, exhibit complex spatial and temporal patterns of co-activity between segregated brain regions. These so-called large-scale resting-state functional connectivity networks represent dynamically organized neural assemblies interacting with each other in a complex way. It has been suggested that looking at the dynamical properties of complex patterns of brain functional co-activity may reveal neural mechanisms underlying the dynamic changes in functional interactions. Here, we examine how global network dynamics is shaped by different network configurations, derived from realistic brain functional interactions. We focus on two main dynamics measures: synchrony and variations in synchrony. Neural activity and the inferred hemodynamic response of the network nodes are simulated using a system of 90 FitzHugh-Nagumo neural models subject to system noise and time-delayed interactions. These models are embedded into the topology of the complex brain functional interactions, whose architecture is additionally reduced to its main structural pathways. In the simulated functional networks, patterns of correlated regional activity clearly arise from dynamical properties that maximize synchrony and variations in synchrony. Our results on the fast changes of the level of the network synchrony also show how flexible changes in the large-scale network dynamics could be.


Identification and characterization of BRDT: A testis-specific gene related to the bromodomain genes RING3 and Drosophila fsh.
The RING3 gene encodes a 90-kDa mitogen-activated nuclear protein. In proliferating cells, including in leukemia, RING3 has serine-threonine kinase and autophosphorylation activities. The cloning of D26362, a gene closely related to RING3, suggests a gene family. RING3 and D26362 are also related to the Drosophila developmental gene fsh. A database search for further members of the RING3 family identified an EST derived from a testis-specific library. cDNA clones representing the full coding sequence of the gene were isolated. The gene encodes a protein of 947 amino acids with extensive homology to RING3, D26362, and fsh. Similar to these proteins, it possesses two bromodomain motifs and a PEST sequence. Northern analysis of 16 normal tissues and eight cancer cell lines shows transcripts of 3.5 and 4.0 kb expressed specifically in testis. The gene has been named BRDT (for bromodomain, testis specific). PCR analysis of a panel of monochromosomal human/rodent hybrid cell lines and the GeneBridge 4 panel of radiation hybrids localizes the gene to chromosome 1p between markers WI-7719 and WI-3099 (D1S2154).


Predicting the Influence of Streamflow on Migration and Spawning of a Threatened Diadromous Fish, the Australian Grayling Prototroctes Maraena.
The development of effective strategies to restore the biological functioning of aquatic ecosystems with altered flow regimes requires a detailed understanding of flow-ecology requirements, which is unfortunately lacking in many cases. By understanding the flow conditions required to initiate critical life history events such as migration and spawning, it is possible to mitigate the threats posed by regulated river flow by providing targeted environmental flow releases from impoundments. In this study, we examined the influence of hydrological variables (e.g., flow magnitude), temporal variables (e.g., day of year) and spatial variables (e.g., longitudinal position of fish) on two key life history events (migration to spawning grounds and spawning activity) for a threatened diadromous fish (Australian grayling Prototroctes maraena) using data collected from 2008 to 2015 in the Bunyip-Tarago river system in Victoria. Our analyses revealed that flow changes act as a cue to downstream migration, but movement responses differed spatially: fish in the upper catchment showed a more specific requirement for rising discharge to initiate migration than fish in the lower catchment. Egg concentrations peaked in May when weekly flows increased relative to the median flow during a given spawning period. This information has recently been incorporated into the development of targeted environmental flows to facilitate migration and spawning by Australian grayling in the Bunyip-Tarago river system and other coastal systems in Victoria.


Lignin and Mn peroxidase-catalyzed oxidation of phenolic lignin oligomers.
The oxidation of phenolic oligomers by lignin and manganese peroxidases was studied by transient-state kinetic methods. The reactivity of peroxidase intermediates compound I and compound II was studied with the phenol guaiacol along with a beta-O-4 phenolic dimer, trimer, and tetramer. Compound I of both peroxidases is much more reactive than compound II. The rate constants for these substrates with Mn peroxidase compound I range from 1.0 x 10(5) M-1 s-1 for guaiacol to 1.1 x 10(3) M-1 s-1 for the tetramer. Reactivity is much higher with lignin peroxidase compound I with rate constants ranging from 1.2 x 10(6) M-1s-1 for guaiacol to 3.6 x 10(5) M-1 s-1 for the tetramer. Rate constants with compound II are much lower with Mn peroxidase exhibiting very little reactivity. The rate constants dramatically decreased with both peroxidases as the size of the substrate increased. The extent of the decrease was much more dramatic with Mn peroxidase, leading us to conclude that, despite its ability to oxidize phenols, Mn2+ is the only physiologically significant substrate. The rate decrease associated with increasing substrate size was more gradual with lignin peroxidase. These data indicate that whereas Mn peroxidase cannot efficiently directly oxidize the lignin polymer, lignin peroxidase is well suited for direct oxidation of polymeric lignin.


National perspective on iron therapy as a clinical performance measure for maintenance hemodialysis patients.
The Health Care Financing Administration (HCFA) End-Stage Renal Disease (ESRD) Core Indicators Project collects clinical information on prevalent adult patients receiving in-center hemodialysis care in the United States to assess the quality of care delivered. Although hematocrit values, transferrin saturations (TSATs) and iron prescription practices have improved over the last 5 years, we sought to determine whether there are continued opportunities for improvement of this domain of care. A random sample of 7,292 adult in-center hemodialysis patients was selected for the period October through December 1996. Hematocrit values, TSATs, serum ferritin concentrations, epoetin-alfa dosing, and iron prescriptions were abstracted from 4,991 patient medical records to assess anemia management practices. The mean hematocrit for this cohort was 32.6% +/- 3.5%, and 72% of patients had hematocrit values greater than 30%. Ninety-four percent of patients received epoetin alfa intravenously, with a mean weekly epoetin dose of 202.4 +/- 137.2 U/kg. The mean TSAT was 27.4% +/- 12.6%; 73% of patients had TSATs >/= 20%. The mean serum ferritin concentration was 386 +/- 422 ng/mL; 79% and 12% of patients had serum ferritin concentrations greater than 100 ng/mL and greater than 800 ng/mL, respectively. Nine percent of the sample had TSATs less than 20% and serum ferritin concentrations less than 100 ng/mL. Regardless of the TSAT, approximately three fourths of patients received iron; only about half received IV iron. Of the subset of patients with TSATs less than 20% and serum ferritin concentration less than 800 ng/mL, only 53% were prescribed IV iron. Although substantial improvements have been made in anemia management in hemodialysis patients over the last 5 years, significant opportunities persist to improve iron prescription practices.


Effects of chromium supplementation on serum high-density lipoprotein cholesterol levels in men taking beta-blockers. A randomized, controlled trial.
To determine the efficacy of glucose tolerance factor (GTF)-chromium for increasing serum levels of high-density lipoprotein (HDL) cholesterol in patients taking beta-blockers. Randomized, double-blind, placebo-controlled trial. Mixed primary and referral-based outpatient clinic at a university-affiliated VA Medical Center. Referred sample of 72 men receiving beta-blockers, mainly for hypertension. Sixty-three patients (88%) completed the study. Current medications, including beta-blockers, were continued. During the 8-week treatment phase, patients in the chromium group received a total daily dose of 600 micrograms of biologically active chromium divided into three equal doses; control patients received a placebo of identical appearance and taste. Serum levels of total cholesterol and HDL cholesterol were measured. Mean baseline levels of HDL and total cholesterol (+/- SD) were 0.93 +/- 0.28 mmol/L and 6.0 +/- 1.0 mmol/L (36 +/- 11.1 mg/dL and 232 +/- 38.5 mg/dL), respectively. The difference between groups in adjusted mean change in HDL cholesterol levels, accounting for baseline HDL cholesterol levels, age, weight change, and baseline total cholesterol levels, was 0.15 mmol/L (5.8 mg/dL) (P = 0.01) with a 95% Cl showing that the treatment effect was greater than +0.04 mmol/L (+1.4 mg/dL). Mean total cholesterol, triglycerides and body weight did not change significantly during treatment for either group. Compliance as measured by pill count was 85%, and few side effects were reported. Two months after the end of treatment, the between-group difference in adjusted mean change from baseline to end of post-treatment follow-up was -0.003 mmol/L (-0.1 mg/dL). Two months of chromium supplementation resulted in a clinically useful increase in HDL cholesterol levels in men taking beta-blockers.


Anomalous constitution of the brachioradialis muscle: a potential site of radial nerve entrapment.
The anatomical relationships of structures in the elbow region in the context of surgical approaches require to be studied carefully and diligently. The main aim of the present study is to report an accessory muscle in the elbow region which was detected during routine anatomical dissection and discuss its clinical importance. The muscle belly measured 4.8 x 2.1cm and it fused with the brachioradialis distally. Proximally, it was seen to blend with the deltoid and the brachialis muscles. The radial nerve was observed to interpose between this accessory muscle and the brachioradialis. This could act as a potential site of compression neuropathy. The present study seeks to elucidate the morphology and potential function of an additional muscle belly in relation to the brachioradialis muscle. A comprehensive knowledge of the anatomical characteristics of brachialis, brachioradialis and radial nerve should prove extremely helpful for the hand surgeons to considerably reduce the risk of injury during operative maneuvers.


The mediation effect of social support between stigma and social alienation in patients with stroke.
Social alienation is prevalent and causes adverse outcomes in stroke. Previous studies have linked stigma with social alienation. However, little is known about the mechanisms behind this relationship. This study explored the mediation effects of social support between stigma and social alienation. A cross-sectional design was used to study 248 patients with stroke admitted to a tertiary rehabilitation hospital in Beijing, China, from December 2022 to July 2023. Patients were assessed using a general information questionnaire, the Stroke Stigma Scale, the Social Support Rating Scale, and the Generalized Social Alienation Scale. The PROCESS macro in SPSS was used to examine the mediation model. The results showed that stigma has a negative effect on social support (β = -0.503, p<0.001); stigma has a positive effect on social alienation (β = 0.768, p<0.001). Social support mediated the relationship between stigma and social alienation, with a mediation effect of 0.131 (95%CI: 0.060, 0.214), and indirect effects accounted for 17.06% of the total effect. Social support mediated the relationship between stigma and social alienation. These findings suggest that intervention targeting the enhancement of social support may prevent or reduce social alienation among patients with stroke.


Immunolocalization of three novel smooth muscle-specific proteins in salivary gland pleomorphic adenoma: assessment of the morphogenetic role of myoepithelium.
Myoepithelial cells of salivary glands have a complex cytoskeletal immunophenotype. To elaborate the smooth muscle phenotype of salivary gland myoepithelium and to assess its contribution to the histogenesis of pleomorphic adenomas, we evaluated the immunohistochemical expression of three novel monoclonal antibodies (MAbs) to alpha smooth muscle actin (alpha-SMA), smooth muscle myosin heavy chains (SMMH), and calponin in formalin-fixed tissues of 65 pleomorphic adenomas (51 contained surrounding normal salivary gland as well). Different cell types within the pleomorphic adenomas were classified as inner tubular epithelial cells, myoepithelium-like cells (juxtatubular, cuboidal, and spindle), modified myoepithelium (myxoid, chondroid, hyaline), and transformed myoepithelium (solid epithelioid, squamous, basaloid-cribriform). Periacinar and periductal myoepithelial cells of all of the 51 normal salivary glands were diffusely stained by all of the 3 MAbs, whereas all of the acinar/ductal epithelial cells were entirely negative. Of 65 pleomorphic adenomas, 61 (94%) reacted to all of the 3 MAbs. None of the smooth muscle markers stained the inner-tubular epithelial cells. Both alpha-SMA and SMMH were essentially limited to the myoepithelium-like cells, whereas modified and transformed myoepithelia lacked these myofilaments. Calponin was found in 64 (98%) of the tumors, reacting to almost all of the myoepithelium-like cells, to 60% of the modified myoepithelium, and to 30% of the transformed myoepithelium. We found the expression of these smooth muscle-specific proteins in the neoplastic myoepithelium to be associated with morphologic differentiation. Alpha-SMA and SMMH are only expressed in better differentiated neoplastic myoepithelium. Calponin is the most sensitive marker of neoplastic myoepithelium, and its identification in different cell types of pleomorphic adenomas denotes a major histogenetic role of myoepithelial cells.


Two types of galactosylated fucose motifs are present on N-glycans of Haemonchus contortus.
N-Glycans from the nematode Haemonchus contortus (barber pole worm), a parasite of sheep and cattle, were the first to be described to possess up to three fucose residues associated with the N,N'-diacetylchitobiosyl core, two being on the reducing-terminal proximal GlcNAc and one on the distal core GlcNAc residue. The assumption was that truncated glycans from this organism with three hexose residues have the composition Man3GlcNAc2Fuc1-3. In this study, we have performed HPLC and MALDI-TOF MS/MS in combination with selected digestions of N-glycans from Haemonchus. A dominant trifucosylated Hex3HexNAc2Fuc3 glycan was modified not only with α1,6-fucose but also with a proximal core α1,3-fucose and a galactosylated distal α1,3-fucose; thereby, only two of the hexose residues were mannose. Other N-glycans displayed galactosylation of the core α1,6-fucose, antennal fucosylation or modification with phosphorylcholine. Thus, the N-glycans of Haemonchus contain a number of potentially immunogenic glycan epitopes also found in other parasites and our proposed structures are in line with the previously defined specificity of nematode glycosyltransferases as we show that distal fucosylation and the presence of an α1,6-mannose are apparently mutually exclusive. These data are thereby of importance for engineering cell lines capable of mimicking Haemonchus-type N-glycans in the preparation of recombinant proteins as vaccine candidates.


State estimation for anaerobic digesters using the ADM1.
The optimization of full-scale biogas plant operation is of great importance to make biomass a competitive source of renewable energy. The implementation of innovative control and optimization algorithms, such as Nonlinear Model Predictive Control, requires an online estimation of operating states of biogas plants. This state estimation allows for optimal control and operating decisions according to the actual state of a plant. In this paper such a state estimator is developed using a calibrated simulation model of a full-scale biogas plant, which is based on the Anaerobic Digestion Model No.1. The use of advanced pattern recognition methods shows that model states can be predicted from basic online measurements such as biogas production, CH4 and CO2 content in the biogas, pH value and substrate feed volume of known substrates. The machine learning methods used are trained and evaluated using synthetic data created with the biogas plant model simulating over a wide range of possible plant operating regions. Results show that the operating state vector of the modelled anaerobic digestion process can be predicted with an overall accuracy of about 90%. This facilitates the application of state-based optimization and control algorithms on full-scale biogas plants and therefore fosters the production of eco-friendly energy from biomass.


RANAVIRUS EPIZOOTIC IN CAPTIVE EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) WITH CONCURRENT HERPESVIRUS AND MYCOPLASMA INFECTION: MANAGEMENT AND MONITORING.
Frog virus 3 (FV3) and FV3-like viruses are members of the genus Ranavirus (family Iridoviridae) and are becoming recognized as significant pathogens of eastern box turtles (Terrapene carolina carolina) in North America. In July 2011, 5 turtles from a group of 27 in Maryland, USA, presented dead or lethargic with what was later diagnosed as fibrinonecrotic stomatitis and cloacitis. The presence of FV3-like virus and herpesvirus was detected by polymerase chain reaction (PCR) in the tested index cases. The remaining 22 animals were isolated, segregated by severity of clinical signs, and treated with nutritional support, fluid therapy, ambient temperature management, antibiotics, and antiviral therapy. Oral swabs were tested serially for FV3-like virus by quantitative real-time PCR (qPCR) and tested at day 0 for herpesvirus and Mycoplasma sp. by conventional PCR. With oral swabs, 77% of the 22 turtles were FV3-like virus positive; however, qPCR on tissues taken during necropsy revealed the true prevalence was 86%. FV3-like virus prevalence and the median number of viral copies being shed significantly declined during the outbreak. The prevalence of herpesvirus and Mycoplasma sp. by PCR of oral swabs at day 0 was 55% and 68%, respectively. The 58% survival rate was higher than previously reported in captive eastern box turtles for a ranavirus epizootic. All surviving turtles brumated normally and emerged the following year with no clinical signs during subsequent monitoring. The immediate initiation of treatment and intensive supportive care were considered the most important contributing factors to the successful outcome in this outbreak.


Pelvic Inflammatory Disease in a Pediatric Emergency Department: Epidemiology and Treatment.
Most adolescent cases of pelvic inflammatory disease (PID) are diagnosed in the emergency department (ED). An important step to prevent PID-related morbidity among this high-risk population is to quantify prevalence and microbial patterns and identify testing and treatment gaps. We performed a retrospective, cross-sectional study of all visits by adolescents to an urban children's ED with an International Classification of Diseases, Ninth Revision, diagnosis of PID in 2012. We used standard descriptive statistics to quantify PID diagnoses, sexually transmitted infections (STI) testing, and treatment. Pelvic inflammatory disease was diagnosed in more than 9% of women with a chief complaint of abdominal/pelvic pain. Most diagnosed cases underwent some STI testing, and 40% tested positive. Seventy percent of cases received antibiotics recommended by the Centers for Disease Control and Prevention. There is a high prevalence of PID among adolescents in the pediatric ED. Rates of STI testing and appropriate treatment reveal gaps in diagnosis and management, representing a lost opportunity for identification and treatment of PID/STIs among high-risk adolescents.


A phase 2a study of topical perillyl alcohol cream for chemoprevention of skin cancer.
The chemopreventive and antitumor properties of perillyl alcohol (POH) that were studied preclinically indicate that topical POH inhibits both UVB-induced murine skin carcinogenesis (squamous cell tumor models) and 7,12-dimethylbenz(a)anthracene-induced murine melanoma (transgenic models involving tyrosinase-driven Ras). A previous phase 1 clinical trial in participants with normal-appearing skin showed that topical POH cream was well tolerated at a dose of 0.76% (w/w). Here, we performed a 3-month, double-blind, randomized, placebo-controlled phase 2a trial of two different doses of topical POH in individuals with sun-damaged skin. Participants applied POH cream twice daily to each dorsal forearm. Baseline and end-of-study biopsies were taken from each participant to evaluate whether the topical application of POH was effective in reversing actinic damage as evidenced by normalization of quantitative skin histopathologic scores and change in nuclear chromatin pattern as measured by karyometric analysis. There was a borderline reduction in the histopathologic score of the lower-dose POH group compared with the placebo (P = 0.1), but this was not observed in the high-dose group. However, in the high-dose group, a statistically significant reduction in the proportion of nuclei deviating from normal was observed by the use of karyometric analysis (P < 0.01). There was no statistical significance shown in the lower-dose group. No changes were observed in p53 expression, cellular proliferation (by proliferating cell nuclear antigen expression), or apoptosis in either treatment group compared with the placebo group. These results suggest that whereas our karyometric analyses can detect a modest effect of POH in sun-damaged skin, improved delivery into the epidermis may be necessary.


Isolated limb perfusion electrochemotherapy for the treatment of an advanced squamous cell carcinoma of the hoof in a mare.
A twenty-year-old female saddle horse was referred for evaluation of a seven month, non-healing erosive lesion of the right hind hoof with proliferation and bleeding of the underlying soft tissues. This lesion had been twice surgically treated as a canker but rapidly recurred. Histological examination of the second excision revealed a well-differentiated squamous cell carcinoma. At presentation, the horse was mildly depressed, lame and partially non-weight-bearing on the right hind leg, which exhibited a 10 x 10 cm erosive and proliferative lesion remodeling the hoof. After completing staging procedures, the lesion was approached with surgery and intraoperative electrochemotherapy (ECT) administration of bleomycin in isolated limb perfusion. A second session of surgery and ECT was performed one month later, followed by three additional monthly sessions of ECT. During periodic recheck, the mare showed continuous improvement. One year after presentation, the mare was in complete remission and her gait markedly improved. ECT was well-tolerated and resulted in improved local control of a tumor in a challenging anatomical district.


Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages.
The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.


3D morphable systems via deterministic microfolding for vibrational sensing, robotic implants, and reconfigurable telecommunication.
DNA and proteins fold in three dimensions (3D) to enable functions that sustain life. Emulation of such folding schemes for functional materials can unleash enormous potential in advancing a wide range of technologies, especially in robotics, medicine, and telecommunication. Here, we report a microfolding strategy that enables formation of 3D morphable microelectronic systems integrated with various functional materials, including monocrystalline silicon, metallic nanomembranes, and polymers. By predesigning folding hosts and configuring folding pathways, 3D microelectronic systems in freestanding forms can transform across various complex configurations with modulated functionalities. Nearly all transitional states of 3D microelectronic systems achieved via the microfolding assembly can be easily accessed and modulated in situ, offering functional versatility and adaptability. Advanced morphable microelectronic systems including a reconfigurable microantenna for customizable telecommunication, a 3D vibration sensor for hand-tremor monitoring, and a bloomable robot for cardiac mapping demonstrate broad utility of these assembly schemes to realize advanced functionalities.


Anomalously Small Reorganization Energy of the Half Redox Reaction of Azurin.
Small values of the reorganization energy, 0.2-0.3 eV, were reported by electrochemical kinetic measurements for the half redox reaction of the redox-active protein azurin. This theoretical study explores possible mechanisms for the low activation barrier for electrochemical protein electron transfer: (1) electronic polarizability of the active site, (2) altering protonation states of far-away histidine residues not directly connected to the active site, and (3) a partial desolvation of the protein when attached to the electrode. The last mechanism provides the most robust explanation of the observations. Constraints imposed by the protein fold on its ability to sample the configuration space lead to the breakdown of the fluctuation-dissipation relation (FDR) and a strong separation of the Stokes-shift and variance reorganization energies. The resulting nonergodic kinetic reorganization energy observed experimentally is significantly lowered compared to predictions of standard models based on Gibbsian statistics and the FDR. The fast rate of protein electron transfer is directly related to the ability of the protein scaffold to maintain nonequilibrium statistics of electrostatic fluctuations projected on the electron-transfer reaction coordinate.


[The effect of the coded amino acids on the development of organotypic culture of the different genesis tissues from young and old rats].
The effect of 20 coded amino acids in concentration 10(-12) M was investigated in organotypic tissue culture on the cell proliferation development in myocardium, pancreas, brain cortex tissue (the tissues of meso-, ento- and ectodermal genesis accordingly) explants in 3- and 24-months old rats. The different effect was observed in the tissues of different genesis. The group of low molecular mass hydrophile amino acids with the charge chains stimulated the cell proliferation in the young and old rats. The other group of high molecular mass hydrophobe amino acids stimulated the cell proliferation in the young and old rats brain cortex. The number of active amino acids decreased significantly in the old rats--2 times in the entodermal tissues and 4 times in the meso- and ectodermal tissues, reflecting the disturbances of the amino acid transport by aging.


Crop Management in Controlled Environment Agriculture (CEA) Systems Using Predictive Mathematical Models.
Proximal sensors in controlled environment agriculture (CEA) are used to monitor plant growth, yield, and water consumption with non-destructive technologies. Rapid and continuous monitoring of environmental and crop parameters may be used to develop mathematical models to predict crop response to microclimatic changes. Here, we applied the energy cascade model (MEC) on green- and red-leaf butterhead lettuce (Lactuca sativa L. var. capitata). We tooled up the model to describe the changing leaf functional efficiency during the growing period. We validated the model on an independent dataset with two different vapor pressure deficit (VPD) levels, corresponding to nominal (low VPD) and off-nominal (high VPD) conditions. Under low VPD, the modified model accurately predicted the transpiration rate (RMSE = 0.10 Lm-2), edible biomass (RMSE = 6.87 g m-2), net-photosynthesis (rBIAS = 34%), and stomatal conductance (rBIAS = 39%). Under high VPD, the model overestimated photosynthesis and stomatal conductance (rBIAS = 76-68%). This inconsistency is likely due to the empirical nature of the original model, which was designed for nominal conditions. Here, applications of the modified model are discussed, and possible improvements are suggested based on plant morpho-physiological changes occurring in sub-optimal scenarios.


Single- and Two-Stage, Closed-Tube, Point-of-Care, Molecular Detection of SARS-CoV-2.
Short of a vaccine, frequent and rapid testing, preferably at home, is the most effective strategy to contain the COVID-19 pandemic. Herein, we report on single-stage and two-stage molecular diagnostic tests that can be carried out with simple or no instrumentation. Our single-stage amplification is reverse transcription-loop mediated isothermal amplification (RT-LAMP) with custom-designed primers targeting the ORF1ab and the N gene regions of the virus genome. Our new two-stage amplification, dubbed Penn-RAMP, comprises recombinase isothermal amplification (RT-RPA) as its first stage and LAMP as its second stage. We compared various sample preparation strategies aimed at deactivating the virus while preserving its RNA and tested contrived and patient samples, consisting of nasopharyngeal swabs, oropharyngeal swabs, and saliva. Amplicons were detected either in real time with fluorescent intercalating dye or after amplification with the intercalating colorimetric dye LCV, which is insensitive to sample's PH. Our single RT-LAMP tests can be carried out instrumentation-free. To enable concurrent testing of multiple samples, we developed an inexpensive heat block that supports both the single-stage and two-stage amplification. Our RT-LAMP and Penn-RAMP assays have, respectively, analytical sensitivities of 50 and 5 virions/reaction. Both our single- and two-stage assays have successfully detected SARS-CoV-2 in patients with viral loads corresponding to the reverse transcription-quantitative polymerase chain reaction (RT-qPCR) threshold cycle smaller than 32 while operating with minimally processed samples, without nucleic acid isolation. Penn-RAMP provides a 10-fold better sensitivity than RT-LAMP and does not need thermal cycling like PCR assays. All reagents are amenable to dry, refrigeration-free storage. The SARS-CoV-2 test described herein is suitable for screening at home, at the point of need, and in resource-poor settings.


Research of glycosylated granulocyte colony-stimulating factor on mobilizing cell regeneration of bone marrow stem cells and repairing injured myocardium.
To compare the differences between glycosylated and non-glycosylated granulocyte colony-stimulating factor (G-CSF) on mobilizing cell regeneration of bone marrow stem cells and repairing injured myocardium. In the acute myocardial ischemia model, 40 Sprague-Dawley rats (8 weeks old, weight 200-250 g) were successfully established with isoproteronol (ISO) and randomly and evenly divided into 4 groups: Group G (injected with glycosylated G-CSF), Group N (non-glycosylated G-CSF), Group C ([control] normal saline for 7 days), and Group M (model). At day 5, all rats were labeled with bromodeoxyuridine (BrdU). At day 28, the proportion of CD34+ cells, myocardial BrdU immunohistochemical stain, myocardial capillary density, myocardial fibrosis and cardiac function was detected among the 3 groups. The study was carried out at the Central Laboratory, Tongji Hospital of Tongji University, Shanghai, China between 1 July 2009 and 31 July 2009. In Group G, the proportion of CD34+ cells and cardiac function was significantly higher than groups N and C, and BrdU positive cells in myocardium were higher than those other groups. Diaminobenzidine stained positive cells in striated muscle tissue possessed more cardiocyte-like structure, higher myocardial capillary density, and less myocardial fibrosis in group G compared with other 2 groups. Glycosytated G-CSF might possess stronger capability to mobilize cell regeneration of bone marrow stem cells and repair injured myocardium.


Parkinson's disease: a complex interplay of mitochondrial DNA alterations and oxidative stress.
Parkinson's disease (PD) is one of the most common age-related neurodegenerative diseases. This pathology causes a significant loss of dopaminergic neurons in the Substantia Nigra. Several reports have claimed a role of defective nuclear and mitochondrial DNA repair pathways in PD etiology, in particular, of the Base Excision Repair (BER) system. In addition, recent findings, related to PD progression, indicate that oxidative stress pathways involving c-Abl and GST could also be implicated in this pathology. This review focuses on recently described networks most likely involved in an integrated manner in the course of PD.


In vitro comparison of the circulaire and AeroTee to a traditional nebulizer T-piece with corrugated tubing.
Nebulizers are a popular means of delivering aerosolized medication, primarily albuterol, to the bronchial airways of patients, and there has been extensive research done on numerous nebulizers used with nebulizer T-pieces and corrugated tubing. Very little research has been performed on other types of nebulizer delivery systems and there is no substantial information on how effective various nebulizer delivery systems are in terms of the quantity and particle size of aerosolized medication delivered to the patient. In this study the Circulaire and the AeroTee, two devices that rely on bags to store aerosol during patient exhalation, are evaluated and compared to the conventional nebulizer T-piece with corrugated tubing. Three each of the nebulizer T-piece with corrugated tubing, the Circulaire, and the AeroTee were sampled using 3 Vixone nebulizers. Each one of the 3 nebulizer delivery systems used the same 3 Vixone nebulizers. Each nebulizer delivery system was evaluated by connecting a constant-flow vacuum and compressed gas source cycled to simulate patient breathing at a respiratory rate of 14 breaths/min and an inspiration-expiration ratio of 1:2. Medication delivered was determined by sampling a portion of the simulated patient's flow onto a membrane filter and calculating the total medication received by the patient. Particle size was determined by sampling with a cascade impactor under ambient conditions. The Circulaire delivered significantly less medication than the nebulizer T-piece with corrugated tubing (p < 0.001), whereas the AeroTee delivered substantially more medication than the nebulizer T-piece with corrugated tubing (p < 0.001). The particle size delivered by the Circulaire was significantly smaller than that of the nebulizer T-piece with corrugated tubing (p < 0.001), whereas the AeroTee delivered particle size equivalent to a nebulizer T-piece with corrugated tubing (p = 0.82). There are clinically important differences between nebulizer delivery systems. When evaluating the optimum means for delivering aerosolized medication, equal consideration should be given to both the brand of nebulizer and the nebulizer delivery system.


Miniplate osteosynthesis in fracture surgeries: Case series with review of concepts.
Miniplates were initially developed as targets for foot and hand fractures, but they have been used in the treatment of fixation of small bone fragments, reduction of long bone fractures and non-union treatment, which have been difficult to treat. In this study, the authors used miniplates to treat fractures of the upper extremities, lower extremities, and pelvis obtained good outcomes. Herein, the authors report these good outcomes and review the current concept of miniplates. Forty-two patients treated with miniplates between March 2012 and March 2017 who attended follow-up for > 1 year were included in this retrospective study. Miniplates were selected according to purpose, which was classified into three categories: fixation, reduction, and stability enhancement. For fixation, miniplates were used to fix distal fibular fractures occurring distal to the syndesmosis and treat patellar and olecranon fractures with severe comminution. For reduction, miniplates were used to reduce the tibia during intramedullary nailing in tibiofibular shaft fractures, while reduction was performed in advance of definitive plating fixation in patients with humeral and pelvic fractures. To enhance stability, the miniplate was inserted after autobone graft for atrophic nonunion at the humeral shaft following nail insertion. The validity of a miniplate was analyzed by reviewing the published literature on the use of miniplates in orthopedic fracture surgeries. Bony union was achieved in all cases. No specific postoperative complications were observed; however, mild pain and limited range of motion observed in two patients were resolved after implant removal. Sixteen studies on fracture treatment using miniplates reported clinically fair outcomes. Miniplates are not just small metal plates. Depending on the location and treatment of the fracture, the miniplate can effectively fix small bone fragments, help the main plate to maintain the reduction of large bone fragments, and increase the fixation force for nonunion treatment.


Warming Increases Pollen Lipid Concentration in an Invasive Thistle, with Minor Effects on the Associated Floral-Visitor Community.
Climate warming is likely to change the ways in which plants interact with their insect mutualists, for example through changes in phytochemistry. In particular, this may have implications for the ways in which we manage noxious weeds, which may spread more quickly if they experience stronger mutualistic interactions. We grew the invasive nodding thistle, Carduus nutans, in two experimental treatments in the field: either passively warmed with open top chambers or at ambient temperatures. We collected pollen from thistles in each treatment and analysed the total protein, lipid, and carbohydrate content. We observed no difference in the pollen protein or carbohydrate content, but the total lipid content of the pollen was significantly higher in warmed plants. We conducted a total of 12.75 h of observations of putatively mutualistic, flower-visiting insects. In addition, we spent 4.17 h collecting bees that visited thistle inflorescences in the treatments, allowing us to identify them to species. We found a significant increase in the abundance of flower-visiting insects in the observations, but not bee abundance in collections. In addition, there was no treatment effect on the number of flower-visiting morphotypes in the observations, or bee species richness in the collections. However, a nonparametric test did identify a significant effect of warming on the composition of flower-visiting morphotypes in observations and bee species in collections. Overall, the warming treatment significantly increased lipid content of the pollen, but had relatively weak effects on insect visitation patterns. However, these effects may be amplified at larger spatial and temporal scales or higher temperatures.


A Deep-Learning Driven Investigation of the Circuit Basis for Reflexive Hypersensitivity to Thermal Pain.
Objectively measuring animal behavior is vital to understanding the neural circuits underlying pain. Recent progress in machine vision has presented unprecedented scope in behavioral analysis. Here, we apply DeepLabCut (DLC) to dissect mouse behavior on the thermal-plate test - a commonly used paradigm to ascertain supraspinal contributions to noxious thermal sensation and pain hypersensitivity. We determine the signature characteristics of the pattern of mouse movement and posture in 3D in response to a range of temperatures from innocuous to noxious on the thermal-plate test. Next, we test how acute chemical and chronic inflammatory injuries sensitize mouse behaviors. Repeated exposure to noxious temperatures on the thermal plate can induce learning. In this study, we design a novel assay and formulate an analytical pipeline to facilitate the dissection of plasticity mechanisms in pain circuits in the brain. Last, we record and test how activating Tacr1 expressing PBN neurons (PBNTacr1) - a population responsive to sustained noxious stimuli- affects mouse behavior on the thermal plate test. Taken together, we demonstrate that by tracking a single body part of a mouse, we can reveal the behavioral signatures of mice exposed to noxious surface temperatures, report the alterations of the same when injured, and determine if a molecularly and anatomically defined pain-responsive circuit plays a role in the reflexive hypersensitivity to thermal pain.


Seminal expression of NY-ESO-1 and MAGE-A4 as markers for the testicular cancer.
Testicular germ cell tumours (TGCTs) are the most common malignancies in Caucasian young men and their incidence has increased over the past decades. However, a non-invasive test allowing an early diagnosis of TGCT often proves inaccurate. We have previously shown that two Cancer-Testis Antigens (CTA), namely MAGE-A4 and NY-ESO-1, were expressed by TGCT. As exfoliation of carcinoma in situ (CIS) cells or tumour germ cells from testis into seminal fluid can occur, here we studied the expression of the 2 CTA in semen smears of patients with testicular cancer in comparison with healthy men. Using semen smears from healthy controls (n = 65) and patients diagnosed for testicular tumour (n = 57) and immunological staining, we observed expression of MAGE-A4 and NY-ESO-1 proteins in seminal fluid exfoliated cells. We found a highly statistically significant difference in the ratios of stained cells to the total number of round cells between testicular cancer patients and healthy controls. Multivariable analysis, including sperm parameters and immunostaining on sperm smears, shows the improvement. This technique can provide towards testicular cancer diagnosis when it is included in the current testing regime. However, the fact that expression of these markers was not restricted to foetal germ cells led to detection in the semen of a number of healthy subjects. Although the detection of these CTA could be useful to characterize the sub-type of individual TGCTs better, we stress here that the false positive rate precludes the exclusive employment of these CTA for the early detection of testicular neoplasia.


Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages.
As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents.


Prevalence of scabies and impetigo in school-age children in Timor-Leste.
Scabies and impetigo are endemic in many tropical, low- and middle-income countries. Mass drug administration (MDA) with ivermectin has emerged as a control strategy for these conditions. In 2019, Timor-Leste Ministry of Health planned to implement MDA including ivermectin for the control of lymphatic filariasis, so we undertook a baseline assessment of scabies and impetigo to better understand local epidemiology and contribute to future surveys assessing the impact of MDA. A cross-sectional school survey was conducted in April-May 2019 at six primary schools in a semi-urban (Dili) and two rural (Ermera and Manufahi) settings. Children under 19 years of age present at school on survey days were eligible to participate, of whom we enrolled 1183. Trained health workers interviewed and examined 1043 participants to clinically diagnose scabies using the 2020 International Alliance for the Control of Scabies (IACS) diagnostic criteria, as well as impetigo. Prevalence was adjusted for age and sex. Mixed-effects logistic regression models were used to analyse odds of scabies and impetigo infection. All models accounted for clustering at the school level through the use of random effect terms. Population attributable risk of scabies as a cause of impetigo was also estimated. The overall weighted prevalence of scabies was 30.6%. Children in rural Manufahi were more likely to have scabies than those in semi-urban Dili (53.6% vs 28.2%, adjusted odds ratio [AOR] 3.5). Most cases of scabies were mild (3 to 10 lesions), and lesions were usually distributed on more than one body region. Scabies prevalence was lower among 10 to 14 year olds compared to 5 to 9 year olds. Overall weighted prevalence of impetigo was 11.3%. Relative to Dili, children in rural Ermera and Manufahi were twice as likely to have impetigo. Impetigo was twice as common in children with scabies than in those without, corresponding to an attributable risk of scabies as a cause of impetigo of 22.7%. Scabies and impetigo prevalence in Timor-Leste is among the highest reported globally, particularly in rural areas. Scabies infestation was strongly associated with impetigo. Comprehensive control strategies are urgently needed in Timor-Leste.


Trends in oral health status: United States, 1988-1994 and 1999-2004.
This report presents national estimates and trends for a variety of oral health status measures for persons aged 2 years and older by sociodemographic and smoking status since the late 1980s in the United States. Data from the third National Health and Nutrition Examination Survey (NHANES III), 1988-1994 and from the NHANES 1999-2004 were used. These data sources were designed to provide information on the health and nutritional status of the civilian noninstitutionalized population in the United States. Information from oral health examination methods common to both survey periods were used to present prevalence estimates and for trend analyses. Statistical significance of differences between common estimates from each survey period was evaluated using two-sided t-tests. This report provides mean, percentile values, and standard errors for dental caries, dental sealants, incisal trauma, periodontal health, dental visits, perception of oral health status, tooth retention, and edentulism. Additional estimates for monitoring progress toward the Healthy People 2010 oral health objectives using NHANES source data are presented as well. For most Americans, oral health status has improved between 1988-1994 and 1999-2004. For seniors, edentulism and periodontitis has declined; for adults, improvements were seen in dental caries prevalence, tooth retention, and periodontal health; for adolescents and youths, dental sealant prevalence has increased and dental caries have decreased; however, for youths aged 2-5 years, dental caries in primary teeth has increased.


Speed and distance requirements for community ambulation: a systematic review.
To provide an overview of the research literature on distance and speed requirements for adults to walk outside the home. We conducted a systematic review and searched PubMed, MEDLINE (Ovid), EMBASE, CINAHL, Scopus, PEDro, and The Cochrane Library from 1948 to May 2012, and other sources. Search terms included communities, walk, ambulation, and neighborhood. Full-text peer-reviewed articles written in English, French, or Spanish reporting distance and/or speed requirements for individuals walking outside the home were considered eligible. Two authors independently screened titles and abstracts. One author reviewed full-text articles to determine inclusion. Of the 3191 titles and abstracts screened, 15 studies (.47%) were selected for detailed review. One author appraised methodological quality. Inadequate description of the reliability of the measurement methods and the population of the town/city assessed was noted. One author extracted data from included studies. A second reviewer independently verified extracted data for accuracy. Seven studies examining 24 community sites and crosswalks in the United States, Australia, and Singapore were included. Three sites with the largest mean distance requirements for adults to walk were club warehouses (677m), superstores (183-607m), and hardware stores (566m). Three sites with the lowest mean distance requirements were walking at the front (16m) and back (19m) of the house, and at cemeteries (18m). The average speed required to cross the street in the time of a walk signal varied from .44 to 1.32m/s. Distance and speed requirements for adults to walk in the community environment vary widely. Findings are relevant to judging capacity for community ambulation to carry out essential activities of daily living, educating patients, and setting rehabilitation goals.


Salmonella in pigs and animal feeding stuffs in England and Wales and in Denmark.
A comparison has been made between the incidence of salmonellas in pigs and feeding stuffs in England and Wales and in Denmark. In Denmark there is veterinary legislation requiring the sterilization of imported and home produced feed ingredients of animal origin. There is no such legislation in England and Wales. In Denmark 0.3% of resterilized imported meat and bone meal was contaminated with salmonellas. This compared with 23% of meat and bone meal in England and Wales and 20-27% of other ingredients of animal origin. In England and Wales salmonellas were isolated from 7% of caecal samples and 6% of lymph node samples, while in Denmark they were isolated from 3% of caecal samples and 4% of lymph node samples. In England and Wales 25 serotypes were found in both pigs and feeds and these included nearly all the most prevalent human pathogens. In Denmark four of the six serotypes in pigs had been found in resterilized feed. One notable difference between the two studies was the very wide range of serotypes found in pigs in England and Wales and the narrow range in Denmark. A second was that Salmonella typhimurium formed 15% of all Salmonella strains isolated from pigs in England and Wales, and 60% of those in Denmark.It is concluded that sterilization of animal raw ingredients in Denmark has reduced pig infections with types other than S. typhimurium that are found in England and Wales, but not with S. typhimurium. It is possible that this is because S. typhimurium once introduced into pigs is able to establish itself more easily than other serotypes.


Spine Oncology-Metastatic Spine Tumors.
Surgery for spinal metastases remains the mainstay treatment for pain, instability, and neurological deterioration due to tumor infiltration of the spine. However, several new therapies are emerging which may improve outcomes further, and in some cases even replace the need for surgery. We now have a better understanding of which factors influence survival and quality of life after surgery, and this underpins the development and application of new treatments, and assessment of outcome.Depending on genetic subtyping of tumors, novel immunotherapies and chemotherapies may be very effective in prolonging quality of life. New surgical techniques allow smaller, quicker, and safer operations with less blood loss, pain, and quicker recovery after surgery. Radiation treatments have also leapt forward with the greater accuracy and higher doses possible from intensity-modulated photon radiation, stereotactic body radiation treatment, proton beam therapy, or carbon ion treatment. Combined with more advanced materials for vertebral body stabilization, computer navigation systems, and robotics, more can be done at earlier or later stages of the spinal disease than was previously possible, resulting in more options and improved outcomes for patients.


Do agonistic motives matter more than anger? Three studies of cardiovascular risk in adolescents.
Three motivational profiles have been associated with recurring psychological stress in low-income youth and young adults: Striving to control others (agonistic striving), striving to control the self (transcendence striving), and not asserting control (dissipated striving). Agonistic striving has been associated with elevated ambulatory blood pressure during daily activities. Three studies tested the hypotheses that: (1) agonistic striving is associated with poor anger regulation, and (2) agonistic striving and poor anger regulation interactively elevate blood pressure. Motivational profiles, anger regulation, and ambulatory blood pressure were assessed in a multiethnic sample of 264 urban youth. (1) anger regulation/recovery during laboratory challenge; (2) anger/blood pressure during daily activities (48 hours). Replication of the profiles in distant cities showed they occur with similar frequency across differences of region, race, and gender. Analyses controlling for body size, race, and gender revealed that individuals with the agonistic striving profile had higher ambulatory pressure, especially during social encounters. They became more openly angry and aggressive when challenged but did not exhibit difficulty regulating anger in the laboratory, nor did they feel angrier during monitoring. However, individuals with the agonistic striving profile who did display poor anger regulation in the lab had the highest blood pressure; deficient self-regulatory capability amplified the positive association between agonistic striving and cardiovascular risk in both genders and all ethnic groups. Although anger is thought to increase cardiovascular risk, present findings suggest that anger and elevated blood pressure are coeffects of agonistic struggles to control others.


Hot days induced by precipitation deficits at the global scale.
Global warming increases the occurrence probability of hot extremes, and improving the predictability of such events is thus becoming of critical importance. Hot extremes have been shown to be induced by surface moisture deficits in some regions. In this study, we assess whether such a relationship holds at the global scale. We find that wide areas of the world display a strong relationship between the number of hot days in the regions' hottest month and preceding precipitation deficits. The occurrence probability of an above-average number of hot days is over 70% after precipitation deficits in most parts of South America as well as the Iberian Peninsula and Eastern Australia, and over 60% in most of North America and Eastern Europe, while it is below 30-40% after wet conditions in these regions. Using quantile regression analyses, we show that the impact of precipitation deficits on the number of hot days is asymmetric, i.e. extreme high numbers of hot days are most strongly influenced. This relationship also applies to the 2011 extreme event in Texas. These findings suggest that effects of soil moisture-temperature coupling are geographically more widespread than commonly assumed.


Prevalence of dementia over age 100.
All nine persons aged 100 or older in a Dutch town with some 100,000 inhabitants were examined by means of cognitive tests, informant questionnaires, and clinical interviews. Formal testing was difficult in most subjects because of visual, auditory, and motor handicaps. By combining the results of cognitive tests and clinical examinations, a diagnosis of moderate to severe dementia could be made in eight subjects. One subject was not examined but by informant questionnaire was found to be mildly demented.


Sound analysis to model weight of broiler chickens.
The pattern of body weight gain during the commercial growing of broiler chickens is important to understand growth and feed conversion ratio of each flock.The application of sound analysis techniques has been widely studied to measure and analyze the amplitude and frequency of animal sounds. Previous studies have shown a significant correlation (P ≤ 0.001) between the frequency of vocalization and the age and weight of broilers. Therefore, the aim of this study was to identify and validate a model that describes the growth rate of broiler chickens based on the peak frequency of their vocalizations and to explore the possibility to develop a tool capable of automatically detecting the growth of the chickens based on the frequency of their vocalizations during the production cycle. It is part of an overall goal to develop a Precision Livestock Farming tool that assists farmers in monitoring the growth of broiler chickens during the production cycle. In the present study, sounds and body weight were continuously recorded in an intensive broiler farm during 5 production cycles. For each cycle the peak frequencies of the chicken vocalizations were used to estimate the weight and then they were compared with the observed weight of the birds automatically measured using on farm automated weighing devices. No significant difference is shown between expected and observed weights along the entire production cycles; this trend was confirmed by the correlation coefficient between expected and observed weights (r = 96%, P value ≤ 0.001).The identified model used to predict the weight as a function of the peak frequency confirmed that bird weight might be predicted by the frequency analysis of the sounds emitted at farm level. Even if the precision of the weighing method based on sounds investigated in this study has to be improved, it gives a reasonable indication regarding the growth of broilers opening a new scenario in monitoring systems in broiler houses.


Hepatobiliary transport mechanism for the cyclopentapeptide endothelin antagonist BQ-123.
The hepatobiliary transport of an anionic cyclopentapeptide endothelin antagonist, BQ-123, was studied in rats. Biliary excretion of [3H]BQ-123 was extensive in vivo (approximately 75% of intravenous infusion rates). Liver-to-plasma and bile-to-liver concentration ratios at steady state were approximately 3 and 200, respectively, suggesting that hepatic uptake and biliary excretion are concentrative processes. The biliary excretion clearance exhibited a saturation at a hepatic concentration of > 100 nmol/g liver and was markedly reduced in Eisai hyperbilirubinemic rats, which have a hereditary defect of canalicular multispecific organic anion transporter. An ATP-dependent and saturable uptake of BQ-123 by isolated canalicular membrane vesicles was observed in vitro. Impaired transport of BQ-123 was also confirmed in canalicular membrane vesicles prepared from Eisai hyperbilirubinemic rats. These results demonstrate that the biliary excretion process is ATP-driven primary active transport. It is proposed that a canalicular multispecific organic anion transporter is mainly responsible for the biliary excretion of BQ-123.


The role of maintenance phototherapy in cutaneous T-cell lymphoma.
Phototherapy is well-recognized as effective therapy in early stage cutaneous T-cell lymphoma (patch and plaque), often resulting in complete clearance of clinical disease and subsequent remission. Although not curable, long-term remission can often be attained utilizing maintenance phototherapy, consisting of a course of less frequent treatments over time. Herein, the authors review the literature regarding the role of maintenance phototherapy in cutaneous T-cell lymphoma (CTCL) and its success in prolonging clinical remission and disease-free survival in CTCL.


Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.
Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p < 0.05) which were confirmed by histopathological examination. Additionally, arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p < 0.05) and decreased activity of thioredoxin reductase, values of total anti-oxidant capacity, and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression. Significant improvement in all assessed parameters was observed in rat group treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.


Posttranscriptional regulation of cytochrome c expression during the developmental cycle of Trypanosoma brucei.
We examined the expression of a nucleus-encoded mitochondrial protein, cytochrome c, during the life cycle of Trypanosoma brucei. The bloodstream forms of T. brucei, the long slender and short stumpy trypanosomes, have inactive mitochondria with no detectable cytochrome-mediated respiration. The insect form of T. brucei, the procyclic trypanosomes, has fully functional mitochondria. Cytochrome c is spectrally undetectable in the bloodstream forms of trypanosomes, but during differentiation to the procyclic form, spectrally detected holo-cytochrome c accumulates rapidly. We have purified T. brucei cytochrome c and raised antibodies that react to both holo- and apo-cytochrome c. In addition, we isolated a partial cDNA to trypanosome cytochrome c. An examination of protein expression and steady-state mRNA levels in T. brucei indicated that bloodstream trypanosomes did not express cytochrome c but maintained significant steady-state levels of cytochrome c mRNA. The results suggest that in T. brucei, cytochrome c is developmentally regulated by a posttranscriptional mechanism which prevents either translation or accumulation of cytochrome c in the bloodstream trypanosomes.