3β-HSD expression in the CNS of a manakin and finch.
The prohormone, dehydroepiandrosterone (DHEA) circulates in vertebrate blood with the potential for actions on target tissues including the central nervous system (CNS). Many actions of DHEA require its conversion into more active products, some of which are catalyzed by the enzyme 3β-hydroxysteroid-dehydrogenase/isomerase (3β-HSD). Studies of birds show both expression and activity of 3β-HSD in brain and its importance in regulating social behavior. In oscine songbirds, 3β-HSD is expressed at reasonably high levels in brain, possibly linked to their complex neural circuitry controlling song. Studies also indicate that circulating DHEA may serve as the substrate for neural 3β-HSD to produce active steroids that activate behavior during non-breeding seasons. In the golden-collared manakin (Manacus vitellinus), a sub-oscine bird, low levels of courtship behavior are displayed by males when circulating testosterone levels are basal. Therefore, we asked whether DHEA circulates in blood of manakins and whether the brain expresses 3β-HSD mRNA. Given that the spinal cord is a target of androgens and likely important in regulating acrobatic movements, we also examined expression of this enzyme in the manakin spinal cord. For comparison, we examined expression levels with those of an oscine songbird, the zebra finch (Taeniopygia guttata), a species in which brain, but not spinal cord, 3β-HSD has been well studied. DHEA was detected in manakin blood at levels similar to that seen in other species. As described previously, 3β-HSD was expressed in all zebra finch brain regions examined. By contrast, expression of 3β-HSD was only detected in the manakin hypothalamus where levels were greater than zebra finches. In spinal cord, 3β-HSD was detected in some but not all regions in both species. These data point to species differences and indicate that manakins have the substrate and neural machinery to convert circulating DHEA into potentially active androgens and/or estrogens.


Impact of tonsillectomy on pediatric psychological status.
Tonsillectomy is one of the most commonly performed procedures in children. However, parents often hesitate to agree to the procedure because of concerns of the possible harmful impact on their child's psychological health. The present study was performed to examine the short-term psychological impact on children who had undergone tonsillectomy. Forty-three pediatric patients aged 3-11 years who underwent tonsillectomy were enrolled in the study. Postoperative pain was assessed using a 10-point visual analog scale (VAS) on postoperative days 1, 2, 7, and 21. The Korean version of the Child Behavior Checklist (K-CBCL) was given to the parents of the children to evaluate the psychosocial effect of tonsillectomy on the preoperative day and on postoperative day 21. There were no significant differences in postoperative pain according to age, tonsil size, degree of adhesion, or operation time. There was no significant relationship between postoperative pain score and K-CBCL score. Sociality, total behavioral problems, externalizing problems, internalizing problems, anxiety/depression, social immaturity, and emotional lability domain scores on the K-CBCL were improved significantly. Improvements in general emotional and social status were observed at 3 weeks after tonsillectomy. Tonsillectomy itself does not have a harmful effect on children's psychological status.


IV nicotine self-administration in rats using the consummatory operant licking response.
Nicotine self-administered by tobacco smoking or chewing is very addictive in humans. Rat models have been developed in which nicotine is self-administered IV by the rats pressing a lever. However the reinforcing value of nicotine is much less in these models than the addictiveness of human tobacco use would indicate. The IV nicotine self-administration operant lever press model does not fully capture important aspects of tobacco use in humans. Conditioned oral consumption actions of smoking or chewing tobacco may play important roles in tobacco addiction. Neural circuitry underlying essential food consummatory responses may facilitate consummatory aspects of tobacco intake. To capture this motor consummatory aspect of tobacco addiction in the rat model of nicotine self-administration, we have developed a method of using a licking response instead of a lever press to self-administer IV nicotine. Sprague-Dawley rats were trained to lick one of two waterspouts for IV nicotine (0.03mg/kg/infusion). With the licking response rats self-administered stable nicotine levels throughout 24 sessions (45min each) of testing. The number of total licks/session significantly increased in a linear fashion over that period. The number of licks/infusion was substantial, rising steadily with training to an average of over 100 licks/infusion. Including the consummatory motor act with nicotine self-administration could help better model the compulsive aspects of tobacco addiction in humans.


Brazilian begomovirus populations are highly recombinant, rapidly evolving, and segregated based on geographical location.
The incidence of begomovirus infections in crop plants sharply increased in Brazil during the 1990s following the introduction of the invasive B biotype of the whitefly vector, Bemisia tabaci. It is believed that this biotype transmitted begomoviruses from noncultivated plants to crop species with greater efficiency than indigenous B. tabaci biotypes. Either through rapid host adaptation or selection pressure in genetically diverse populations of noncultivated hosts, over the past 20 years various previously unknown begomovirus species have became progressively more prevalent in cultivated species such as tomato. Here we assess the genetic structure of begomovirus populations infecting tomatoes and noncultivated hosts in southeastern Brazil. Between 2005 and 2010, we sampled and sequenced 126 DNA-A and 58 DNA-B full-length begomovirus components. We detected nine begomovirus species in tomatoes and eight in the noncultivated host samples, with four species common to both tomatoes and noncultivated hosts. Like many begomoviruses, most species are obvious interspecies recombinants. Furthermore, species identified in tomato have probable parental viruses from noncultivated hosts. While the population structures of five well-sampled viral species all displayed geographical subdivision, a noncultivated host-infecting virus was more genetically variable than the four predominantly tomato-infecting viruses.


Sensory manipulation results in increased dorsolateral prefrontal cortex activation during static postural balance in sedentary older adults: An fNIRS study.
The dorsolateral prefrontal cortex (DLPFC) is involved with allocating attentional resources to maintain postural control. However, it is unknown whether age-related structural and functional declines of the DLPFC may impair postural control during sensory manipulation. In this study, we aim to understand the effects of aging on the DLPFC when sensory cues were removed or presented inaccurately (i.e., increased sensory complexity) during the sensory orientation test (SOT). Twenty young (18-25 years) and 18 older (66-73 years) healthy adults were recruited to undertake the SOT, which consisted of six conditions aimed at removing or disrupting the visual, vestibular, and proprioceptive senses. During these six SOT conditions, functional near-infrared spectroscopy (fNIRS), consisting of eight transmitter-receiver optode pairs (four channels over the left and right DLPFC), was used to measure hemodynamic responses (i.e., changes in oxy- [O2 Hb] and deoxyhemoglobin [HHb]) from the bilateral DLPFC. Our results show an increase in bilateral DLPFC activation (i.e., increase in O2 Hb and concomitant smaller decrease in HHb) with increasing sensory complexity in both young and older adults. The increase in left and right DLPFC activation during more complex sensory conditions was greater, which was concomitant with reduced balance performance in older adults compared to younger adults. Furthermore, we observed a right lateralized DLPFC activation in younger adults. Finally, a significant positive association was observed between balance performance and increased bilateral DLPFC activation particularly for SOT conditions with greater sensory disruptions. Our findings highlight the involvement of the DLPFC in maintaining postural control, particularly during complex sensory tasks, and provide direct evidence for the role of the DLPFC during postural control of a clinically relevant measure of balance.


[Inflammation and structural organ damage: chicken or egg?].
It is not inflammation but functional and/or anatomical loss of integrity of target organs that is the major determinant of morbidity in many immune-mediated inflammatory diseases (IMIDs). This structural and often irreversible tissue damage is generally considered to be a direct or indirect consequence of inflammation (through failed repair mechanisms). However, recent clinical observations in rheumatic diseases, demonstrate clearly that the postulated causal relationship between inflammation and structural damage does certainly not hold true in all IMIDs. On the contrary, potent anti-inflammatory treatments suggest an uncoupling of inflammation and damage in diseases such as ankylosing spondylitis. The author proposes a third and intriguing alternative hypothesis: inflammation and stromal remodelling are causally linked but it is the latter that drives the former. If this hypothesis is correct, we should focus our therapeutic efforts on pathways of tissue remodelling rather than on inflammation in IMIDs such as ankylosing spondylitis, but potentially also scleroderma or asthma.


Relationship of the surface structure of metaphase chromosomes to the higher order organization of chromatin fibers.
Scanning electron microscopy (SEM), as well as transmission electron microscopy (TEM), has been utilized to determine how the surface structure of mitotic chromosomes is related to the organization of the 30 nm chromosomal fibers. SEM revealed the surfaces of isolated, HeLa cell chromosomes to possess a knobby substructure with chromosomes prepared for EM in buffers containing 0.5-1.5 mM Mg2+. These projections had substantially greater widths (65-70 nm) than the underlying chromatin fibers. Reducing the Mg ion concentration to 0.05-0.15 mM resulted in the further expansion of the chromosomes, which flattened the chromosomes for SEM so the fibers became the dominant feature of the micrographs. The surface protuberances are interpreted as representing the peripheral tips of radial chromatin loops. The same procedure of slightly expanding chromosomes by decreasing the Mg2+ concentration in resuspension buffer was also utilized in a TEM, serial sectioning study. Longitudinal sections close to the central chromatid axis showed radially oriented fibers within the planes of the sections. This was replaced by a dot pattern when the longitudinal sections grazed the periphery of the chromatid. Transverse sections displayed more clearly the radial orientation of the fibers. A consistent picture emerges from applying SEM and TEM that supports the "radial loop" model for the primary mode of organization of chromatin fibers in metaphase chromosomes.


[Surgical approach to retinal vein occlusion].
Retinal vein occlusions are the second most common vision threatening retinal vascular disorders. Our therapeutic armamentarium for functional improvement was very limited in the past for all types of retinal vein occlusions (branch, central and hemi-central retinal vein occlusion). Also pathomechanism and risk factors are not completely understood yet. Argon-laser-photocoagulation can prevent the development and treat neovascularizations successfully, but is unable to improve visual function in most cases. Thrombolytic therapy applied systemically is limited due to serious side effects but may be helpful when injected intraocularly. Isovolemic hemodilution may be efficacious in central retinal vein occlusion (CRVO). The creation of a laser-induced chorioretinal venous anastomosis showed serious complications. Since 1999 numerous reports on successful surgical techniques were published. It could be shown that the dissection of the adventitial sheath with separation of the artery from the vein at the arteriovenous crossing where branch retinal vein occlusion occurs can re-establish the retinal blood flow with reduction of macular edema. But it is still unclear which step of the surgery (vitrectomy, ILM-peeling, sheathotomy) is causative for the results. A new surgical approach in CRVO is the radial optic neurotomy (RON). This technique was primarily performed under the hypothesis of decompression of the central vein by cutting the scleral ring. Meanwhile there is some evidence that the formation of chorioretinal shunts may be the decisive factor in cases of successfully performed RON. Due to inconsistent and rare data this surgical procedure needs further evaluation. Another surgical option is the cannulation of the occluded vein. This technique seems to be feasible but the clinical results still have to be proved. Despite several uncertainties and open questions, surgical techniques are likely to overcome the desolate therapeutic situation for retinal vein occlusion of the past.


Atherogenic Lipoprotein Determinants of Cardiovascular Disease and Residual Risk Among Individuals With Low Low-Density Lipoprotein Cholesterol.
Levels of LDL (low-density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid-related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low-density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo-allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non-high-density lipoprotein cholesterol, and triglycerides, but not LDL-c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On-statin levels of the smallest VLDL particle subclass were associated with a 68% per-SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk-this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C-index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein-related risk were observed. Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.


Mapping of retinal and geniculate neurons onto striate cortex of macaque.
A unity ratio between geniculate and ganglion cells can be shown in the macaque visual system. Comparison of the densities (cells/deg2) in the dorsal lateral geniculate nucleus (dLGN) of parvocellular (P) and magnocellular (M) cells, respectively, representing color-opponent and broad-band ganglion cells, with cortical magnification (mm2/deg2) gives the number of afferents per square millimeter in striate cortex (V1). For P cells, this afferent density rises only slightly with eccentricity, indicating that V1 magnification is approximately proportional to the density of P cells. The density of cytochrome oxidase puffs in V1 also rises only slightly with eccentricity. As a result, the number of P-cell afferents per puff-centered module is remarkably constant throughout V1. Our findings thus support a novel hypothesis of peripheral scaling, in which V1 cortical magnification is based on the mapping of just 1 class of afferent onto V1 modules. This "P-cell module" in V1 may be composed of submodules corresponding anatomically to the honeycomb cell in layer 4A of V1 and physiologically to a minimal complete set of color-opponent ganglion cells. In contrast, the afferent density of M cells rises steeply with eccentricity, so that the reciprocal of their afferent density, the cortical "domain" of M cells, declines with eccentricity. This decline is similar to that of point-image area in V1. As a result, the number of M cells per point-image area is nearly constant. This quantity is analogous to the receptive-field coverage factor in the retina, which for M cells is fairly constant and greater than unity at all eccentricities. The results show fundamental differences between the neural maps of these 2 major cell types, differences that are likely to have psychophysical consequences.


Hereditary gingival fibromatosis.
Hereditary gingival fibromatosis (HGF) is a rare condition that can occur as an isolated disease, chromosomal abnormality, or as part of a number of syndromes. The gingival enlargement in HGF can be so severe that it can cover the crowns of teeth completely, causing severe functional derangement and facial disfigurement. Through review of literature revealed that HGF is usually an autosomal dominant condition, however the recessive forms are also reported. The hyperplastic gingiva is firm on palpation and has normal color with abundant stippling on the adjacent gingiva. The buccal and lingual gingiva may be involved in both the mandible and maxilla. The degrees of gingival enlargement show both intra- and interindividual variations. Here, an interesting case report of massive HGF has been presented.


Hydrophobic Domain Structure of Linear-Dendritic Poly(ethylene glycol) Lipids Affects RNA Delivery of Lipid Nanoparticles.
In this work, a series of linear-dendritic poly(ethylene glycol) (PEG) lipids (PEG-GnCm) were synthesized through a strategy using sequential aza- and sulfa-Michael addition reactions. The effect of modulating the hydrophobic domain of linear-dendritic PEG lipids was systematically investigated for in vitro and in vivo small RNA delivery as the surface-stabilizing component of 5A2-SC8 dendrimer lipid-based nanoparticles (DLNPs). The lipid alkyl lengths (C8, C12, and C16) and dendrimer generations (G1, G2, and G3) were altered to create PEG-GnCm with different physical properties and anchoring potential. The tail chemical structure of PEG-GnCm did not affect the formulation of 5A2-SC8 DLNPs, including the nanoparticle size, RNA encapsulation, and stability. However, the tail chemical structure did dramatically affect the RNA delivery efficacy of the formed 5A2-SC8 DLNPs with different PEG-GnCm. First-generation PEG lipids (PEG-G1C8, PEG-G1C12, and PEG-G1C16) and a second-generation PEG lipid (PEG-G2C8) formed 5A2-SC8 DLNPs that could deliver siRNAs effectively in vitro and in vivo. 5A2-SC8 DLNPs formulated with second-generation PEG lipids (PEG-G2C12 and PEG-G2C16) and all three third-generation PEG lipids (PEG-G3C8, PEG-G3C12, and PEG-G3C16) lost the ability to deliver siRNA effectively in vitro and in vivo. Overall, we determined that the hydrophobic domain chemical structure of linear-dendritic poly(ethylene glycol) lipids affected the RNA delivery of DLNPs by impacting the escape of 5A2-SC8 DLNPs from endosomes at early cell incubation times, thereby indicating how PEG lipid anchoring and chemical structure can modulate in vitro and in vivo siRNA delivery efficacies.


Application of digital holographic tomography in antitumor effect of cantharides complex on 4T1 breast cancer cells.
The study focuses on a methodology providing noninvasive monitoring and evaluation of the antitumor effect of traditional Chinese medicine, cantharides complex (canth), on 4T1 breast tumor cells. Digital holographic tomography (DHT) and developed data post-processing algorithms were used for quantitative estimation of changes in optical and morphological parameters of cells. We calculated and compared data on the refractive index, thickness, and projected area of 4T1 breast tumor cells in control untreated specimens and those treated with doxorubicin hydrochloride (DOX), canth, and their combinations. Post-treatment changes in cellular morphology recorded by DHT demonstrated that the two drugs led to noticeably different morphological changes in cells that can be presumably associated with different pathways of their death, apoptosis, or necrosis. The effect of combined treatment with these two drugs strongly depended on their relative concentrations and could lead to changes characteristic either for DOX or for canth; however, being more profound than those obtained when using each drug solely. The results obtained by DHT are in a good correspondence with commonly used cell viability analysis and immunofluorescent analysis of changes in cellular cytoskeleton.


[Treatment of cardiogenic shock due to right ventricular involvement].
The right ventricle is susceptible to changes in preload, afterload, and contractility. The answer is its dilation with dysfunction/acute failure; filling is limited to the left ventricle and cardiac output. Systemic venous congestion is retrograde to the right heart, it is involved in the genesis of cardiogenic shock due to right ventricle involvement. This form of shock is less well known than that which occurs due to left ventricular failure, therefore, treatment may differ. Once the primary treatment has been carried out, since no response is obtained, supportive treatment aimed at ventricular pathophysiology will be the next option. It is suggested to evaluate the preload for the reasoned indication of liquids, diuretics or even ultrafiltration. Restore or maintain heart rate and sinus rhythm, treat symptomatic bradycardia, arrhythmias that make patients unstable, use of temporary pacing or cardioversion procedures. Improving contractility and vasomotility, using vasopressors and inotropes, alone or in combination, the objective will be to improve right coronary perfusion pressure. Balance the effect of drugs and maneuvers on preload and/or afterload, such as mechanical ventilation, atrial septostomy and pulmonary vasodilators. And the increasing utility of mechanical support of the circulation that has become a useful tool to preserve/restore right heart function.


[T-lymphocytes disorders in pulmonary sarcoidosis].
Sarcoidosis is a granulomatous disorder of unknown aetiology accompanied by variable immunological changes which concern both the monocyte and lymphocyte cell line. During the course of this disease anomalies of distribution (with accumulation in the disease tissue contrasting with a peripheral lymphopenia) and also of T cell functions (a predominance of CD4 T lymphocytes within the lesions and spontaneous expression of activation criteria) have been described. Recent works show some disturbances of T cell function and evoke the possibility of the initial pathology being related to this cell. Some current hypotheses place the T cell receptor for the antigen and the interleukin 2 receptor whose dysfunction will lead to an anomaly of the transduction of the activating signal of the T lymphocyte. The intrinsic origin (genetically determined) or extrinsically (retroviral) of these disturbances remains however to be determined.


Dengue Virus Serotypes 1 and 2 Responsible for Major Dengue Outbreaks in Nepal: Clinical, Laboratory, and Epidemiological Features.
Dengue virus (DENV) is expanding toward previously nonendemic areas. DENV has recently been introduced in Nepal with limited information. We report the clinical features and serotype distribution of DENV in Nepal during the 2010 outbreaks. A total of 1,215 clinical dengue cases at two major hospitals of central and western Nepal were investigated. Demographic, clinical, and laboratory parameters were recorded. Serum specimens were tested for DENV by IgM/IgG enzyme-linked immunosorbent assays (ELISAs) and reverse transcription polymerase chain reaction (RT-PCR). We confirmed DENV infection in 403 (33%) patients from 12 districts with an estimated case fatality rate of 1.5%. DENV infection was more common in adults (87%) and urban settings (74%). We detected all four serotypes but DENV-1 and -2 were mainly responsible for major outbreaks (92%). Overall, 60% of all DENV infections were secondary and 17% were severe dengue; both being more frequent among the DENV-2 infections. Rash, bleeding, abdominal pain, hepatomegaly, elevated liver enzymes, and thrombocytopenia were significantly more common in severe dengue compared with nonsevere infections. We also confirmed the expansion of dengue to hill urban areas (DENV-1 and -2), including the capital Kathmandu (altitude, 1,300 m) though > 90% cases were from southern plains. Differential clinical and laboratory features probably help in clinical decisions. Multiple serotypes circulation and elevated secondary infections pose potential risk of severe outbreaks and deaths in the future. Therefore, a country with recent dengue introduction, like Nepal, urgently requires a systematic surveillance and appropriate control measures in place to respond to any disastrous outbreaks.


Training the motor cortex by observing the actions of others during immobilization.
Limb immobilization and nonuse are well-known causes of corticomotor depression. While physical training can drive the recovery from nonuse-dependent corticomotor effects, it remains unclear if it is possible to gain access to motor cortex in alternative ways, such as through motor imagery (MI) or action observation (AO). Transcranial magnetic stimulation was used to study the excitability of the hand left motor cortex in normal subjects immediately before and after 10 h of right arm immobilization. During immobilization, subjects were requested either to imagine to act with their constrained limb or to observe hand actions performed by other individuals. A third group of control subjects watched a nature documentary presented on a computer screen. Hand corticomotor maps and recruitment curves reliably showed that AO, but not MI, prevented the corticomotor depression induced by immobilization. Our results demonstrate the existence of a visuomotor mechanism in humans that links AO and execution which is able to effect cortical plasticity in a beneficial way. This facilitation was not related to the action simulation, because it was not induced by explicit MI.


Monitoring the Heart Rate Variability Responses to Training Loads in Competitive Swimmers Using a Smartphone Application and the Banister Impulse-Response Model.
First, to examine whether heart rate variability (HRV) responses can be modeled effectively via the Banister impulse-response model when the session rating of perceived exertion (sRPE) alone, and in combination with subjective well-being measures, are utilized. Second, to describe seasonal HRV responses and their associations with changes in critical speed (CS) in competitive swimmers. A total of 10 highly trained swimmers collected daily 1-minute HRV recordings, sRPE training load, and subjective well-being scores via a novel smartphone application for 15 weeks. The impulse-response model was used to describe chronic root mean square of the successive differences (rMSSD) responses to training, with sRPE and subjective well-being measures used as systems inputs. Changes in CS were obtained from a 3-minute all-out test completed in weeks 1 and 14. The level of agreement between predicted and actual HRV data was R2 = .66 (.25) when sRPE alone was used. Model fits improved in the range of 4% to 21% when different subjective well-being measures were combined with sRPE, representing trivial-to-moderate improvements. There were no significant differences in weekly group averages of log-transformed (Ln) rMSSD (P = .34) or HRV coefficient of variation of Ln rMSSD (P = .12); however, small-to-large changes (d = 0.21-1.46) were observed in these parameters throughout the season. Large correlations were observed between seasonal changes in HRV measures and CS (changes in averages of Ln rMSSD: r = .51, P = .13; changes in coefficient of variation of Ln rMSSD: r = -.68, P = .03). The impulse-response model and data collected via a novel smartphone application can be used to model HRV responses to swimming training and nontraining-related stressors. Large relationships between seasonal changes in measured HRV parameters and CS provide further evidence for incorporating a HRV-guided training approach.


Differential transcriptional profiles mediated by exposure to the cannabinoids cannabidiol and Δ9-tetrahydrocannabinol in BV-2 microglial cells.
Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. We previously showed that the psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways. To characterize the transcriptional effects of CBD and THC, we treated BV-2 microglial cells with these compounds and performed comparative microarray analysis using the Illumina MouseRef-8 BeadChip platform. Ingenuity Pathway Analysis was performed to identify functional subsets of genes and networks regulated by CBD and/or THC. Overall, CBD altered the expression of many more genes; from the 1298 transcripts found to be differentially regulated by the treatments, 680 gene probe sets were up-regulated by CBD and 58 by THC, and 524 gene products were down-regulated by CBD and only 36 by THC. CBD-specific gene expression profile showed changes associated with oxidative stress and glutathione depletion, normally occurring under nutrient limiting conditions or proteasome inhibition and involving the GCN2/eIF2α/p8/ATF4/CHOP-TRIB3 pathway. Furthermore, CBD-stimulated genes were shown to be controlled by nuclear factors known to be involved in the regulation of stress response and inflammation, mainly via the (EpRE/ARE)-Nrf2/ATF4 system and the Nrf2/Hmox1 axis. These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity. This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.


Insulin therapy for critically ill hospitalized patients: a meta-analysis of randomized controlled trials.
Hyperglycemia is common in critically ill hospitalized patients, and it is associated with adverse outcomes, including increased mortality. The objective of this meta-analysis was to determine the effect of insulin therapy initiated during hospitalization on mortality in adult patients with a critical illness. An electronic search in the English-language articles of MEDLINE and the Cochrane Controlled Clinical Trials Register and a hand search of key journals and relevant review articles were performed. Randomized controlled trials that reported mortality data on critically ill hospitalized adult patients who were treated with insulin were selected. Data on patient demographics, hospital setting, intervention (formulation and dosage of insulin, delivery method, and duration of therapy), mortality outcomes, adverse events, and methodological quality were extracted. Thirty-five trials met the inclusion criteria. Combining data from all trials using a random-effects model showed that insulin therapy decreases short-term mortality by 15% (relative risk [RR], 0.85; 95% confidence interval [CI], 0.75-0.97). In subgroup analyses, insulin therapy decreased mortality in the surgical intensive care unit (RR, 0.58; 95% CI, 0.22-0.62), when the aim of therapy was glucose control (RR, 0.71; 95% CI, 0.54-0.93), and in patients with diabetes mellitus (RR, 0.73; 95% CI, 0.58-0.90). A near-significant trend toward decreasing mortality was seen in patients with acute myocardial infarction who did not receive reperfusion therapy (RR, 0.84; 95% CI, 0.71-1.00). No randomized trials of insulin in the medical intensive care unit were identified. Insulin therapy initiated in the hospital in critically ill patients has a beneficial effect on short-term mortality in different clinical settings.


Analysis of the Clinical Characteristics, Management, and Causes of Death in Patients with ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention from 2005 to 2014.
It is unknown whether there has been any change in the causes of death for acute ST-segment elevation myocardial infarction (STEMI) in the era of aggressive reperfusion. We analyzed the direct causes of in-hospital death in patients with STEMI treated with primary percutaneous coronary intervention (PCI) in a tertiary referral center over the past 10 years.We retrospectively analyzed 878 STEMI patients treated with primary PCI in our hospital between January 2005 and December 2014. There were no significant changes in the age and sex of patients, but the prevalence of hypertension and smoking decreased. STEMI severity increased with more patients in Killip classification > 2. The number of out-ofhospital cardiac arrest events also increased over the 10 years. Symptom onset-to-door time did not change in the 10year study period. The care quality was improved with shorter door-to-balloon time for primary PCI and increased use of dual antiplatelet therapy. The all-cause in-hospital mortality was 9.1%, which did not vary over the 10 years. Multivariable analysis showed that Killip classification > 2 was the most important determinant of death. Cardiogenic shock was the major cause of cardiovascular death. There was an increase in non-cardiovascular causes of death in the most recent 3 years, with infection being a major problem.Despite improvement in care quality for STEMI, the in-hospital mortality did not decrease in this tertiary referral center over these 10 years due to increased disease severity and non-cardiovascular causes of death.


Monitoring of fetuses with retarded BPD growth.
Retarded BPD growth (less than 5th centile) is associated with low birth weight, preterm delivery, and increased perinatal mortality. However, 50% of the fetuses with deviating BPD growth in the 32nd week have normal weight at birth. In this study other biochemical and physical tests were applied to a group of fetuses with deviating BPD growth in order to improve the discriminatory rate between infants subsequently born AGA or SGA. Measurements of the ratio abdomen to head diameter were above the 50th centile in 72% of the infants born AGA and below the 50th centile in 75% of those born SGA. Circumference measurements were less useful in our hands. Urinary oestriol levels were not directly proportional to the intrauterine growth retardation. Recording of fetal breathing movements and nonstressed monitoring of fetal heart rate FHR) had little or no predictive value in the individual case although the incidence of fetal breathing movements was significantly lower in the group with retarded BPD growth.


Azide-alkyne "click" conjugation of 8-aza-7-deazaadenine-DNA: synthesis, duplex stability, and fluorogenic dye labeling.
The internal dye labeling of DNA by the Huisgen-Meldal-Sharpless "click" reaction is described. Fluorogenic 9-azidomethyl anthracene 2 and 3-azido-7-hydroxycoumarin 3 were employed in the postsynthetic functionalization of oligonucleotides incorporating octa-(1,7)-diynyl-8-aza-7-deaza-2'-deoxyadenosine 1. Nucleoside 1 was prepared by Sonogashira cross coupling from the corresponding 7-iodo compound, converted into the corresponding phosphoramidite, and oligonucleotides were synthesized. To evaluate the influence of ligands on the oligonucleotide duplex stability, benzyl azide 4 (nonpolar), and 2',3'-dideoxy azidothymidine 5 (AZT) (polar) were introduced along with the fluorogenic dyes 2 and 3. DNA duplexes with octa-1,7-diynyl side chains (i.e., containing 1) are more stable than oligonucleotides containing 8-aza-7-deaza-2'-deoxyadenosine, unveiling that this side chain has steric freedom. A single conjugation by an anthracene residue led to a 9 °C T(m) increase of duplex melting. Contrary to 7-deazaadenine dye conjugates, the 8-aza-7-deazaadenine conjugates show virtually no fluorescence quenching, thereby developing almost as strong fluorescence as side chain click derivatives (32 and 33) in the absence of 8-aza-7-deazaadenine moiety. Duplexes containing the 8-aza-7-deazaadenine dye conjugate show increased fluorescence over single-stranded DNA. Mismatches with dA, dG, and dC develop reduced fluorescence compared to the fully matched base pair. Molecular dynamics simulations revealed that the bulky dye molecules are accommodated well in duplex DNA.


A Structural Perspective on the Modulation of Protein-Protein Interactions with Small Molecules.
Protein-Protein Interactions (PPIs) are the key components in many cellular processes including signaling pathways, enzymatic reactions and epigenetic regulation. Abnormal interactions of some proteins may be pathogenic and cause various disorders including cancer and neurodegenerative diseases. Although inhibiting PPIs with small molecules is a challenging task, it gained an increasing interest because of its strong potential for drug discovery and design. The knowledge of the interface as well as the structural and chemical characteristics of the PPIs and their roles in the cellular pathways is necessary for a rational design of small molecules to modulate PPIs. In this study, we review the recent progress in the field and detail the physicochemical properties of PPIs including binding hot spots with a focus on structural methods. Then, we review recent approaches for structural prediction of PPIs. Finally, we revisit the concept of targeting PPIs from a systems biology perspective and we refer to approaches that are usually employed when the structural information is not present.


National scale predictions of contemporary and future blue carbon storage.
To help mitigate the impacts of climate change, many nature-based solutions are being explored. These solutions involve protection and restoration of ecosystems that serve as efficient carbon sinks, including vegetated coastal ecosystems (VCEs: tidal marshes, mangrove forests, and seagrass meadows) also known as 'Blue Carbon' ecosystems. In fact, many nations are seeking to manage VCEs to help meet their climate change mitigation targets through Nationally Determined Contributions (NDCs). However, incorporation of VCEs into NDCs requires national-scale estimates of contemporary and future blue carbon storage, which has not yet been achieved. Here we address this challenge using machine learning approaches to reliably map (with 62-72% accuracy) soil carbon stocks in VCEs based on geospatial data (topography, geomorphology, climate, and anthropogenic impacts), using Australia as a case study. The resulting maps of soil carbon stocks showed that there is a total of 951 Tg (±65 Tg) of carbon stock within Australian VCEs. Strong relationships between soil carbon stocks and climatic conditions (temperature, rainfall, solar radiation) allowed us to project future changes in carbon storage across all RCP scenarios for the years 2050 and 2090 to determine changes in environmental suitability for soil carbon stocks. Results show that soil carbon stocks in mangrove/tidal marsh ecosystems are likely to predominantly experience declines in carbon stocks under predicted climate change scenarios (19% of ecosystems area is predicted to have an increase in soil carbon stocks, while 38% of ecosystems area is predicted to have a decrease in soil carbon stocks), but a majority of seagrass area is likely to have increased soil carbon stocks (56% increase, 7% decrease). This approach is effective for developing robust national blue carbon inventories and revealing the capacity for blue carbon to help meet NDCs. The resulting spatially-explicit maps can also be used to pinpoint areas for successful blue carbon projects both now and in the future.


Training and capacity building in obstetric fistula repair: A scoping review.
An ongoing barrier to sustainable obstetric fistula (OF) care is the lack of trained fistula surgeons. Despite a standardized training curriculum, data regarding OF repair training remain limited. To assess the availability of literature on the case numbers or training duration required for OF repair competency and whether these data are stratified by trainee background or repair complexity. A systematic search of MEDLINE, Embase, and OVID Global Health electronic databases and gray literature. All English sources from all years from low- and middle-income and high-income countries were eligible. Identified titles and abstracts were screened and full-text articles were reviewed. Data collection and analysis included a descriptive summary organized by training case numbers, training duration, trainee background, and repair complexity. Of the 405 sources retrieved, 24 were included in the study. The only concrete recommendations were in the International Federation of Gynecology and Obstetrics 2022 Fistula Surgery Training Manual, which proposes 50 to 100 repairs (Level 1), 200 to 300 repairs (Level 2), and trainer discretion for Level 3 competency. More case- or time-based data, particularly if stratified by trainee background and repair complexity, would be useful at the individual, institutional, and policy level for fistula care implementation or expansion.


Person-first and identity-first language: Developing psychologists' cultural competence using disability language.
The American Psychological Association (APA) advocates the use of person-first language (e.g., people with disabilities) to refer to individuals with disabilities in daily discourse and to reduce bias in psychological writing. Disability culture advocates and disability studies scholars have challenged the rationale for and implications of exclusive person-first language use, promoting use of identity-first language (e.g., disabled people). We argue that psychologists should adopt identity-first language alongside person-first constructions to address the concerns of disability groups while promoting human dignity and maintaining scientific and professional rigor. We review the evolution of disability language and then discuss the major models used to characterize disability and people with disabilities. The rationale for person-first language and the emergence of identity-first language, respectively, are linked to particular models. We then discuss some language challenges posed by identity-first language and the current intent of person-first language, suggesting that psychologists make judicious use of the former when it is possible to do so. We conclude by offering five observations of ways that use of both person-first and identity-first language could enhance psychologists' cultural competence regarding disability issues in personal and scientific communications.


[Program offer for the integral development of early childhood in Chile: Scoping review].
To describe the program offering designed to promote comprehensive early childhood de velopment in Chile. A scoping review was carried out following the Joanna Briggs Institute's methodological framework. A researcher conducted the review considering as inclusion criteria go vernment programs aimed at the comprehensive development of children under 5 years of age in Chile. The data were organized and synthesized to describe the characteristics of the program and the service(s) it provides. The search identified 2.060 documents and 72 met the inclusion crite ria. 59 current programs are covering early childhood, which are mainly managed by the Ministries of Justice, Education, Health, and Social Development. Most of the programs are aimed at promotion and intervention, focusing on vulnerable populations, are cross-sectoral, and use different strategies for their implementation. The program offering in Chile for early childhood has charac teristics suggested as effective to promote child development.


[Features of clinical application of eye acupuncture therapy revealed by data mining].
To investigate the features, dominant indications and application regularities of eye acupuncture therapy in clinical practice. We first collected original articles, academic dissertations, conference articles, and case reports from databases of CNKI, Wanfang, and Chinese biomedical literature (CBM) from Jan. 1 of 1980 to Dec. 31 of 2017, and medical records from medical books of Zhonghua Yan Zhen (Chinese Eye Acupuncture Therapy), Yanzhen Shijian Lu (Records of Application of Eye Acupuncture Therapy), and Peng Jing-shan's Yanzhen Liaofa Yanjiu (Peng Jing-shan's Eye Acupuncture Therapy) by using keyword of "eye acupuncture". Then, we established an "Eye-acupuncture Database" after sorting, screening, typing-in, checking, and extraction of the collected data by SQL server 2005 and 2005 Analysis Services (SASS), followed by analysis of the dominant indications, needling methods, needle manipulations, principles for acupoint selection, and clinical effect. Among the 850 articles retrieved, 178 were eligible to be subjected to analysis, including 42 disorders/diseases in 7 categories. The eye acupuncture therapy has the highest application frequency for 19 types of disorders/diseases of the internal medicine, such as sequela of apoplexy, hiccup, insomnia, vertigo, hypertension, etc., followed by head and body pain (7 types: headache, lumbago, sciatica, shoulder pain, etc.), disorders of the ophthalmology and otorhinolaryngology (deafness, squinting eyes, dry eye syndrome, amblyopia, etc.), traumatic injury, gynecopathy, acute pain (biliary colic, renal colic). The effect rate was 95.87% for disorders of the gynecopathy, 95.54% for head and body pain, 94.53% for traumatic skin injury, 92.16% for emergency, 91.98% for disorders of the five sense organs, 91.43% for problems of the internal medicine, etc. Regarding the principle of acupoint selection, acupoints were chosen mainly according to the meridian running (146 articles), local region of the eye (14 articles) and diseased location (153 articles). A total of 157 articles have a marked description about the needling methods, including horizontal needling (81 articles), intra-orbital straight needling (22 articles), extra-orbital oblique needling (13 articles), etc. The duration of needle retaining was mostly from 15 to 30 minutes, and the handle-scraping was frequently adopted (34 articles), and the overall treatment frequency ranged from 11 to 20 times. In regard to the medical records, a total of 53 types of disorders were involved, including 37 types of the internal medicine such as stroke sequelae (34 articles), facial paralysis (11 articles), etc. The acupoints were selected according to the local region of eye (129 articles), the needle insertion involved horizontal needling (102 articles), and cured rate reported was higher than 90%. Eye acupuncture therapy is widely used for a variety of disorders and has a positive effect, particularly for stroke sequelae and various acute and chronic pain problems.


Revision Surgery Following Severe Frostbite Injury Compared to Similar Hand and Foot Burns.
Severe frostbite is associated with loss of digits or limbs and high levels of morbidity. The current practice is to salvage as much of the limb/digit as possible with the use of thrombolytic and adjuvant therapies. Sequelae from amputation can include severe nerve pain and poor wound healing requiring revision surgery. The aim of this study was to examine the rate of revision surgery after primary amputation and compare this to revision surgery in isolated hand/foot burns. Frostbite and burn patients from 2014 to 2019 were identified in the prospectively maintained database at a single urban burn and trauma center. Patients with primary amputations related to isolated hand/foot burns or frostbite were included in the study. Descriptive statistics included Student's t-test and Fisher's exact test. A total of 63 patients, 54 frostbite injuries and 9 isolated hand or foot burns, met inclusion criteria for the study. The rate of revision surgery was similar following frostbite and burn injury (24% vs 33%, P = .681). There were no significant differences in age, sex, or length of stay on the primary hospitalization between those that required revision surgery and those that did not. Neither the impacted limb nor the presence of infection or cellulitis on primary amputation was associated with future need for revision surgery. Of the 16 patients requiring revision surgery, 5 (31%) required additional debridement alone, 6 (38%) required reamputation alone, and 5 required both. A total of 6 patients (38%) had cellulitis or infection at the time of revision surgery. Time from primary surgery to revision ranged from 4 days to 3 years. Planned, delayed primary amputation is a mainstay of frostbite management. To our knowledge, this is the first assessment of revision surgery in the setting of severe frostbite injury. Our observed rate of revision surgery following frostbite injury did not differ significantly from revision surgery in the setting of isolated hand or foot burns. This study brings up important questions of timing and surgical planning in these complex patients that will require a multicenter collaborative study.


Bipolar sealing increases mesenteric reach during bowel transection compared with stapled division: clinical evidence and laboratory support in a porcine model.
The ideal technique for mesenteric division to create tension-free anastomoses has not been defined. For patients undergoing Roux-en-Y gastric bypass (RYGB), the mesenteric division technique was changed from stapler to bipolar sealing using LigaSure for cost reasons. This study aimed objectively to assess the impact of the mesenteric division method on mobilization length of the Roux limb in an animal model. Clinical complications related to Roux limb tension also were analyzed in the authors' population of RYGB patients. Bowel and mesenteric divisions were performed in a porcine model. Four pigs received six to eight mesenteric divisions each. Steady force was applied for 1 min. The distances between the divided limbs of bowel were compared. To assess the clinical impact with RYGB patients, anastomotic complications were analyzed before and after incorporation of bipolar sealing in the authors' practice. In the porcine model, the length of mesenteric stretch averaged 93.7 mm with stapled division and 109 mm with bipolar sealing (p = 0.021). From a laparoscopic RYGB population, 160 patients with stapled division were included, all of whom were at least 1 year beyond their surgery. The study analyzed 792 patients with bipolar sealing for leak or bleeding and included 479 bipolar sealed patients more than 1 year beyond their surgery for analysis of their strictures. No difference in bleeding or leaks was found between these groups. The stricture rate was significantly different, with seven strictures after stapled division (4.37%) compared with one stricture after bipolar sealing (0.2%; p = 0.001). Bipolar sealing for mesenteric division is superior to stapling for optimization of enteric limb length at constant tension in a laboratory model. Clinical evidence supports this hypothesis with patients undergoing RYGB surgery by a decrease in the complications that can arise from Roux limb tension.


Ketoconazole, amphotericin B, and amphotericin B methyl ester: comparative in vitro and in vivo toxicological effects on neutrophil function.
We investigated a number of parameters for host defense after the in vitro addition of the antifungal agents ketoconazole, amphotericin B (AMB), and amphotericin B methyl ester (AME). Similar assays were repeated before and after patients received the former two drugs. Viability by trypan blue exclusion, adherence by nylon wool columns, chemotaxis by the under-agarose technique, phagocytosis and killing by chemiluminescence, colony counts, and acridine orange direct visualization were assayed. In striking contrast to AMB and AME, ketoconazole demonstrated no significant effect on neutrophils. Adherence in the presence of therapeutic plasma levels of AMB and AME was decreased (P less than or equal to 0.005) at low drug concentrations, whereas at higher concentrations, adherence was increased (P less than 0.001). The chemotactic responses of cells incubated with AMB and AME demonstrated marked suppression. Phagocytic capacity and killing were decreased (P less than or equal to 0.005) with AMB as compared with control assays and assays performed in the presence of ketoconazole and AME. However, no difference were observed between two patients who received AMB and two other treated with ketoconazole.


Equity of access to outpatient care and hospitalization among older community residents in Brazil.
To determine whether, as mandated by Brazilian law, health care (outpatient care, hospitalization) among older community residents is based on health-related criteria and not on other characteristics. Cross-sectional, population-representative. Multistage, random sample of 7040 household residents aged >or=60 years in the state of Rio Grande do Sul, Brazil. Structured in-person interviews to determine sociodemographic characteristics, self-reported health conditions, psychiatric status, outpatient service use within the previous 6 months, and number of hospitalizations within the previous 12 months. Seventy two percent reported an outpatient visit, 20% reported hospitalization. In controlled analyses, being female, older, unemployed, having private health insurance, increased the odds of an outpatient visit. Males, older persons, the insured, and more educated were more likely to report hospitalization. Race/ethnicity and religious affiliation were not associated with outpatient or hospital use. Pneumonia, heart disease, and urinary tract infection were particularly associated with both outpatient visits and hospitalization; diabetes, hypertension, and cancer with outpatient visit; stroke, cancer and psychiatric disorder with hospitalization; and heart disease, pneumonia, and psychiatric disorder with multiple hospitalizations. Use of health services did not differ by race/ethnicity or religion, but private health insurance facilitated outpatient access, and increased education facilitated hospitalization. Gender, age, and employment status likely reflected differential health needs. Improved access is needed for older persons lacking private health insurance, and those with little education. Patients with psychiatric problems merit increased attention to reduce excessive hospitalization.


Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis.
Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and the total antioxidant status (TAS) in peripheral lymphocytes of rats during different intraperitoneal gram-negative sepsis stages. Adult male Sprague-Dawley rats were divided randomly into four groups. Control group was intraperitoneally inoculated with 2 mL of pyrogene-free saline (Group I, n = 6), and the other rats received an intraperitoneal inoculum with 2 mL of saline containing 2 x 10(8) CFU of Escherichia coli. The animals were killed at time zero (Group I, n = 6), at 6th (Group II, n = 7), 12th (Group III, n = 7), and 24th (Group IV, n = 7) hour after the E. coli inoculation. Oxidative DNA damage in peripheral lymphocytes of rats was evaluated by modified comet assay (single-cell gel electrophoresis). Formamidopyrimidine DNA glycosylase (Fpg) and Endonuclease III (Endo III) were used to detect oxidized purines and pyrimidines, respectively. Total antioxidant quantification was carried out using ABTS+ (2,2'-Azino-di-[3 ethylbenzthiazoline sulphonate]) radical formation kinetics (Randox kit) in serum samples. Significant elevations of basal levels of strand breaks (SB) in Group IV were observed as compared with Group I, II, and III. There was a significant increase in Fpg sites in Group III as compared with Group I and II. However, there was no significant difference in terms of Endo III sites in any of the groups. Although the TAS was decreased with the stages of sepsis, this moderate decrease was significant in only Group IV as compared with Group I. There was no statistically significant correlation between DNA damage and TAS for any of the groups.


DNA metabarcoding focusing on the plankton community: an effective approach to reconstruct the paleo-environment.
DNA metabarcoding (DNA-MB) targeting the whole plankton community is a promising approach in studies of sediment samples from water bodies, but its effectiveness in ancient material is not well demonstrated. We applied DNA-MB of plankton in a sediment core to reconstruct the paleo-environment of Lake Shinji, Japan, through a marine lagoon/freshwater lake transition during the past 2300 years. We interpreted core-sample plankton taxonomy and habitat by reference to the modern plankton community in water samples. OTUs (operational taxonomic units) belonging to Dictyochophyceae were 81.05% of the total reads in sediments. However, Ciliophora, Copepoda and Labyrinthulea formed the majority of plankton taxa in the water samples, suggesting that they are under-represented in sediment. A drastic change in plankton composition correlated with a large decrease in sediment sulfur concentration, implying the change of aquatic environment from marine lagoon to freshwater lake. This event took place ca. 1200 CE in Lake Shinji. A 250 year-long transitional period followed, during which the total DNA sequence reads were very low. This suggests that salinity fluctuations created a hostile environment for both marine and freshwater plankton species. Our results show that DNA-MB of the whole plankton community is effective in reconstructing paleo-environments.


Monitoring the Effect of Levodopa Using Sustained Phonemes in Parkinson's Disease Patients.
Parkinson's disease (PD) is a neurological disease identified by multiple symptoms, and levodopa is one of the most effective medications for treating the disease. To determine the dosage of levodopa, it is necessary to meet on a regular basis and observe motor function. The early detection and progression of the disease have been proposed using hypokinetic dysarthria. However, previous studies have not examined the effects of levodopa on speech rigorously and have provided inconsistent results. In this study, three sustained phonemes of PD patients were investigated for the effect of medication. A set of features characterizing vocal fold dynamics as well as the vocal tract coordinators were extracted from the sustained phonemes /of 28 PD patients during levodopa medication off and on states. All the features were statistically investigated and classified using a linear discriminant analysis (LDA) classifier. LDA classifier identified medication on from medication off based on the combined features from phoneme /a/, /o/ and /m/ with the accuracy=82.75% and F1-score=82.18%. Voice recording of PD patients during sustained phonemes /a/, /o/ and /m/ has the potential for identifying whether the patients are in On state or Off state of medication.Clinical Relevance- The outcomes of this study have the potential to monitor the effect and progress of levodopa on PD patients.


Minimally Invasive Glaucoma Surgery: Latest Developments and Future Challenges.
The development of minimally invasive glaucoma surgeries (MIGSs) was intended to provide safe and modestly efficacious modalities for early intervention of mild-to-moderate glaucoma, with minimal trauma and rapid recovery. They were mainly ab interno procedures that reduce intraocular pressure by facilitating the aqueous outflow by bypassing the trabecular meshwork resistance, reinforcing the uveoscleral flow via the supraciliary space, and reducing aqueous production by the ciliary body. While the cumulating evidence helps shape the role of the available MIGS, the exponential new development and advancement in this field has expanded the territory of MIGS. Apart from developing subconjunctival MIGS filtration devices (Xen gel stent and PRESERFLO MicroShunt), there is a tendency to revisit the "traditional" MIGS for alternative use and to modify the procedures with consideration of the fundamental aqueous outflow physiology. Combined MIGS has also been suggested, based on the theory that their different mechanisms may provide additive or synergistic effects. The advancement of laser procedures is also promising and could supplement unmet needs along the glaucoma treatment algorithm. This review examines the broad array of MIGS, updates the recent findings, discusses their potential alternative applications, and explores future challenges.


Left Distal Radial Artery Access Site in Primary Percutaneous Coronary Intervention: Is It Safe?
Left distal radial artery access site has emerged as a new technique for coronary angiography procedures. We aimed at assessing its applicability as an alternative way for primary percutaneous coronary interventions in ST-elevation myocardial infarction. Retrospective observational cohort study. Left distal radial artery was used as an access site in 30 consecutive ST-elevation myocardial infarction patients for primary coronary intervention. It was used by experienced operators who were unaware of the study. All patients had a prominent pulse in their left forearm and distal radial artery. Each patient's left arm was gently bent into his/her right groin with comfortable position of the hand. The operator/s stood at the right side of the patient where both could make the arterial puncture. Demographic features and complications were recorded during the hospital stay. Mean age of patients was 58 years with a male gender predominance of 87%. Fifteen patients were diagnosed of Inferior elevation myocardial infarction, 14 patients of Anterior, and one of Lateral elevation myocardial infarction. The most common culprit artery was the left anterior descending coronary artery (14 patients). Six patients were in KILLIP class II on admission and only one with Anterior elevation myocardial infarction was in severe pulmonary edema (KILLIP III) during intervention. All the procedures were successfully contemplated with 6 French Judkins catheters. Brachial spasm occurred in one patient which was resolved with intra-arterial nitrate. Transfemoral approach was changed to left distal radial access in 4 patients due to severe bilateral iliac artery disease. Mean puncture time was 37.36 seconds. There was no radial occlusion, hematoma, hand neurologic deficit or bleeding. Patients were discharged on an average duration of 4.2 days. Left distal radial artery can be used as an alternative safe and feasible access site for successful primary coronary interventions provided that it is performed by experienced operators.


Mobile technology and telemedicine for shoulder range of motion: validation of a motion-based machine-learning software development kit.
Mobile technology offers the prospect of delivering high-value care with increased patient access and reduced costs. Advances in mobile health (mHealth) and telemedicine have been inhibited by the lack of interconnectivity between devices and software and inability to process consumer sensor data. The objective of this study was to preliminarily validate a motion-based machine learning software development kit (SDK) for the shoulder compared with a goniometer for 4 arcs of motion: (1) abduction, (2) forward flexion, (3) internal rotation, and (4) external rotation. A mobile application for the SDK was developed and "taught" 4 arcs of shoulder motion. Ten subjects without shoulder pain or prior shoulder surgery performed the arcs of motion for 5 repetitions. Each motion was measured by the SDK and compared with a physician-measured manual goniometer measurement. Angular differences between SDK and goniometer measurements were compared with univariate and power analyses. The comparison between the SDK and goniometer measurement detected a mean difference of less than 5° for all arcs of motion (P > .05), with a 94% chance of detecting a large effect size from a priori power analysis. Mean differences for the arcs of motion were: abduction, -3.7° ± 3.2°; forward flexion, -4.9° ± 2.5°; internal rotation, -2.4° ± 3.7°; and external rotation -2.6° ± 3.4°. The SDK has the potential to remotely substitute for a shoulder range of motion examination within 5° of goniometer measurements. An open-source motion-based SDK that can learn complex movements, including clinical shoulder range of motion, from consumer sensors offers promise for the future of mHealth, particularly in telemonitoring before and after orthopedic surgery.


Influence of Ankaferd Blood Stopper on shear bond strength of bonding systems.
This study investigated the effect of Ankaferd Blood Stopper (ABS) contamination on bond strength of total- and self-etching systems. Seventy mandibular third molars sectioned in a mesio-distal direction were mounted in acrylic resin, and flat dentin surfaces were exposed. The specimens were randomly assigned to seven groups (n=20), according to the surface treatment: Group I, ABS contamination+37% phosphoric acid+Solobond M; Group II, ABS contamination+Clearfil SE Bond; Group III, ABS contamination+All Bond SE; Group VI, 37% phosphoric acid+ABS contamination+Solobond M; Group V, Solobond M; Group VI, Clearfil SE Bond; and Group VII, All Bond SE. Next, a resin composite (Grandio) was built up using a plastic apparatus and polymerized. The specimens were tested in shear mode at a crosshead speed of 1 mm/min. There were significant differences in bond strengths between the control and ABS-contaminated samples. These findings suggest that ABS contamination reduced bond strength of total- and self-etching adhesives.


Activation of transcription by estrogen receptor alpha and beta is cell type- and promoter-dependent.
Tamoxifen acts as a strong estrogen antagonist in human breast but as an estrogen agonist in the uterus. The action of tamoxifen is mediated through estrogen receptors (ERalpha and ERbeta), which bind to a variety of responsive elements, to activate transcription. To examine the role of these varied elements in the response to antiestrogens, we studied the activation of a panel of differing promoters, by these compounds, in human breast, bone, and endometrial derived cell lines. No agonistic activity was observed in breast cells, whereas all antiestrogens, particularly tamoxifen, exhibited agonistic effects in uterine cell lines. All antiestrogens studied were agonistic in co-transfections of a collagenase reporter gene and ERbeta, but tamoxifen alone was agonistic with ERalpha in (uterine) HEC-1-A cells. The ERalpha mediated, agonism of tamoxifen was not observed in primary cultures of human uterine stromal cells, whereas the ERbeta-mediated agonism of all selective estrogen receptor modulators was present. This suggests that the two receptors operate by distinct pathways and that the response of cells to antiestrogens is dependent on the ER subtypes expressed.


The importance of 'knowing the patient': community nurses' constructions of quality in providing palliative care.
This paper reports findings from a study conducted in one community health care trust where 62 members of the district nursing team (grades B-H) were interviewed. An adaptation of the critical incident technique was used to determine factors which contributed or detracted from high quality care for a number of key areas including palliative care. The centrality of knowing the patient and his/her family emerged as an essential antecedent to the provision of high quality palliative care. Factors enabling the formation of positive relationships were given prominence in descriptions of ideal care. Strategies used to achieve this included establishing early contact with the patient and family, ensuring continuity of care, spending time with the patient and providing more than the physical aspects of care. The characteristics described by the community nurses are similar to those advocated in 'new nursing' which identifies the uniqueness of patient needs, and where the nurse-patient relationship is objectified as the vehicle through which therapeutic nursing can be delivered. The link with 'new nursing' emerges at an interesting time for community nurses. The past decade has seen many changes in the way that community nursing services are configured. The work of the district nursing service has been redefined, making the ideals of new nursing, for example holism, less achievable than they were a decade ago. This study reiterates the view that palliative care is one aspect of district nursing work that is universally valued as it lends itself to being an exemplar of excellence in terms of the potential for realizing the ideals of nursing practice. This is of increasing importance in the context of changes that militate against this ideal.


New perspectives of physiological and pathological functions of nucleolin (NCL).
Nucleolin (NCL) is a multifunctional protein that mainly localized in the nucleolus, it is also found in the nucleoplasm, cytoplasm and cell membrane. The three main structural domains allow the interaction of NCL with different proteins and RNA sequences. Moreover, specific post-translational modifications and its shuttling property also contribute to its multifunctionality. NCL has been demonstrated to be involved in a variety of aspects such as ribosome biogenesis, chromatin organization and stability, DNA and RNA metabolism, cytokinesis, cell proliferation, angiogenesis, apoptosis regulation, stress response and microRNA processing. NCL has been increasingly implicated in several pathological processes, especially in tumorigenesis and viral infection, which makes NCL a potential target for the development of anti-tumor and anti-viral strategies. In this review, we present an overview on the structure, localizations and various functions of NCL, and further describe how the multiple functions of NCL are correlated to its multiple cellular distributions.


The bidirectional longitudinal relationship between insomnia, depression and anxiety in patients with early-stage, medication-naïve Parkinson's disease.
While anxiety, depression and insomnia frequently (co-)occur in Parkinson's disease (PD) patients, little is known about their temporal relationship. In this study, we tested two hypotheses: i) insomnia predicts an increase in symptoms of depression or anxiety and ii) anxiety or depression at baseline predicts insomnia in PD patients six months later. We used longitudinal data from a prospective cohort study of early-stage, medication-naïve PD patients. Primary outcome measures were: anxiety symptoms, measured with the State-Trait Anxiety Inventory (STAI); depressive symptoms, measured with the 15-item Geriatric Depression Scale (GDS-15); and insomnia, defined as a score ≥ 2 on item 1.7 of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale. We performed linear and logistic regression analyses, correcting for baseline value of the respective outcome variable. Baseline insomnia was not associated with GDS-15 or STAI total score at follow-up. In a post hoc analysis, we found that insomnia predicted a higher STAI State score (B(SE) = 2.50 (1.07), p < 0.05), while the association with the STAI Trait score was not significant. Baseline STAI scores (B(SE) = 0.02 (0.01), p = 0.001) and GDS-15 score (B(SE) = 0.15 (0.05), p < 0.001) were significantly associated with insomnia at follow-up. Symptoms of anxiety and depression may constitute a risk factor for insomnia in PD. The relationship between insomnia and anxiety is bidirectional, which suggests that both anxiety and sleep disorders can start a negative spiral in PD patients, where one enhances the other. Independent clinical attention for these symptoms in PD patients is therefore warranted.


The Impact of Glucagon-like peptide-1 (GLP-1) Agonists on Hip and Knee Arthroplasty and Perioperative Considerations.
Glucagon Like Peptide agonists (GLP-1 agonists) have traditionally been used for glycemic control in diabetic patients. However, there has been a dramatic rise in their utilization for weight loss management. As such, arthroplasty surgeons will encounter an increasing number of patients on these medications and therefore it is important to understand the implications of their use in the perioperative period. This review will describe the pharmacological actions of these medications as well as the impact on hip and knee arthroplasty patients and considerations for perioperative management. Because of the rapid adaption and utilization of these drugs, the science is evolving at a fast pace. More and longer-term studies are needed to truly understand the impact of these medications on total joint arthroplasty utilization and in management of these patients in the perioperative period.


Acute Kidney Injury Caused by TAFRO Syndrome in a Chinese Patient: Efficacy of Long-Term Corticosteroids Combined with Bortezomib and Cyclophosphamide.
Thrombocytopenia, ascites, myelofibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome is a newly recognized and rare clinical subtype of Castleman disease. Renal involvement in TAFRO syndrome usually presents with mild proteinuria, microscopic hematuria, and acute renal injury requiring temporary renal replacement. There is no standard therapy available and treatment failures are common, leading to a poor prognosis. We report a case of acute renal failure caused by TAFRO syndrome, successfully managed by long-term corticosteroids combined with bortezomib and cyclophosphamide. The patient was a 52-year-old female who presented with fever, anasarca, oliguria, and abdominal distension at first. She progressed rapidly to anuric renal failure requiring hemodialysis. She also demonstrated thrombocytopenia, anemia, coagulopathy, and a hyperinflammatory status. Her CT scan showed severe polyserositis, splenomegaly, and lymphadenopathy. Her serum vascular epithelial growth factor level was significantly elevated. Axillary lymph node biopsy showed hyaline-vascular type Castleman disease, supporting the diagnosis of TAFRO syndrome. Her renal function recovered after high-dose steroids and supportive treatment. A weekly dosing regimen of bortezomib, cyclophosphamide, and dexamethasone combined with medium dose prednisone in between were deployed. Her blood cell count and renal function remained stable after 6 months. The inflammation was suppressed and the polyserositis resolved completely. TAFRO syndrome is rare and has a poor prognosis due to the lack of standard treatment. Our patient might be the first TAFRO case successfully treated by bortezomib, cyclophosphamide, and corticosteroids.


Effects of transfusing older red blood cells and platelets on obstetric patient outcomes: A retrospective cohort study.
To investigate associations between transfusion of blood products close to the end of shelf-life and clinical outcomes in obstetric inpatients. Mortality and morbidity were compared in patients transfused exclusively with red blood cells (RBC) stored for less than 21 days (fresh) versus RBC stored for 35 days or longer (old), and platelets (PLT) stored for 3 days or fewer (fresh) versus 4 days or longer (old) in Queensland, Australia from 2007 to 2013. Multivariable models were used to examine associations between these groups of blood products and clinical end points. There were 3371 patients who received RBC and 280 patients who received PLT of the eligible storage durations. Patients transfused with old RBC received fewer transfusions (2.7 ± 1.8 vs. 2.3 ± 1.0 units; P < 0.001). However, a higher rate of single-unit transfusions was also seen in those patients who exclusively received old RBC (252 [9.3%] vs. 92 [13.7%]; P = 0.003). Comparison of fresh vs. old blood products revealed no differences in the quantities of transfused RBC (9.5 ± 5.9 vs. 9.1 ± 5.2 units; P = 0.680) or PLT (1.5 ± 0.8 vs. 1.4 ± 1.1 units; P = 0.301) as well as the length of hospital stay for RBC (3 [2-5] vs. 3 [2-5] days; P = 0.124) or PLT (5 [4-8] vs. 6 [4-9] days; P = 0.120). Transfusing exclusively older RBC or PLT was not associated with increased morbidity or mortality.


The Epidemiology of Hip Fracture among Subjects with Pyogenic Liver Abscess (PLA): A Nationwide Population-Based Study.
Pyogenic liver abscess (PLA) is a potentially fatal disease that can stimulate prominent systemic inflammation. Osteoporotic hip fracture is a major complication of systemic inflammation. This study tried to determine the epidemiology of hip fractures among PLA patients. All subjects admitted due to PLA during 1999∼2010 were assessed, excluding the subjects with a history of high energy trauma, malignancy, and previous hip fracture. We matched the control subjects to PLA patients according to age, gender, and the coding of osteoporosis by 1 : 4 ratio. The PLA patients had a 1.17-fold risk of hip fracture than the controls (aHR = 1.17, 95% CI = 1.07-1.29) after adjusting for gender, age, and comorbidities. Considering death as the competing event of suicide, the PLA patients had 1.10-fold suicide risk (aHR = 1.10, 95% CI: 1.00-1.21) than the control subjects under the competing risks regression model. The cumulative incidence of hip fracture was higher in the PLA cohort (log-rank test, p < 0.001). When compared to the controls, the fracture risk was 18.4-fold (aHR = 18.4, 95% CI = 13.0-26.1) for the PLA patients admitted 2-3 times per year and 46.0-fold (aHR = 46.0, 95% CI = 31.2-67.8) for the PLA patients admitted ≧4 times per year. The impact of PLA is more prominent among the subjects aged <45 years (aHR = 2.81, 95% CI = 1.42-5.56). Preventive measures for hip fracture might be warranted for PLA patients.


Coagulopathy in COVID-19 and Its Implication for Safe and Efficacious Thromboprophylaxis.
The novel coronavirus, SARS-CoV-2, is causing a global pandemic of life-threatening multiorgan disease, called COVID-19. Accumulating evidence indicates that patients with COVID-19 are at significant risk of thromboembolic complications, mainly affecting the venous, but also the arterial vascular system. While the risk of venous thromboembolism (VTE) appears to be higher in patients requiring intensive care unit support compared to those admitted to general wards, recent autopsy findings and data on the timing of VTE diagnosis relative to hospitalization clearly suggest that thromboembolic events also contribute to morbidity and mortality in the ambulatory setting. In addition to a severe hypercoagulable state caused by systemic inflammation and viral endotheliitis, some patients with advanced COVID-19 may develop a coagulopathy, which meets established laboratory criteria for disseminated intravascular coagulation, but is not typically associated with relevant bleeding. Similar to other medical societies, the Society of Thrombosis and Haemostasis Research has issued empirical recommendations on initiation, dosing, and duration of pharmacological VTE prophylaxis in COVID-19 patients.


Barriers to telemedicine: survey of current users in acute care units.
The present study of current telemedicine users is a unique attempt to understand the barriers and motivational factors related to the utilization of telemedicine. A survey of emergency and critical care remote presence telemedicine users was conducted to determine the factors that motivate and the barriers that impede the acceptance and maintenance of a robotic telemedicine (RTM) program. The majority of the survey users were in the Emergency Department or in the Intensive Care Unit. E-mail invitations were sent to 483 individuals representing 63 healthcare institutions and groups in North America and Europe. Respondents were directed to a Web-based survey. The survey consisted of 96 separate questions, addressing user familiarity and 5-point Likert scales, addressing issues spanning the conceptual and practical issues surrounding adoption of telemedicine. A total of 106 surveys were completed, representing an individual response rate of 21.9% but an institutional response rate of 60.3%. More than two-thirds of the respondents were physicians who participated in active RTM programs. Across seven different topics related to barriers to implementing RTM, the majority of all respondents indicated that cultural issues did not constitute meaningful hurdles, technological matters were generally favorable, and that most personnel were agreeable to both achieving the buy-in to start an RTM program and to maintaining RTM once started. However, respondents proclaimed that RTM's success was still hampered by licensing, credentialing, and malpractice protection, as well as costs, billing, and reimbursement issues. Achieving immediate patient access, overcoming service gaps, improving quality, providing clinical support, maintaining patient satisfaction, and adhering to practice guidelines were viewed as significant motives for RTM implementation. The leading applications of RTM included emergency response and consultation. The patients, physicians, nurses, nor hospital executives served as barriers to implementation. However, licensing, costs for technology, and reimbursement for RTM continue to impede progress.


Gut microbiota and serum metabolome reveal the mechanism by which TCM polysaccharides alleviate salpingitis in laying hens challenged by bacteria.
This paper aimed to evaluate the effect of 3 kinds of TCM polysaccharides instead of antibiotics in preventing salpingitis in laying hens. After feeding the laying hens with Lotus leaf polysaccharide, Poria polysaccharide, and Epimedium polysaccharide, mixed bacteria (E. coli and Staphylococcus aureus) were used to infect the oviduct to establish an inflammation model. Changes in antioxidant, serum immunity, anti-inflammatory, gut microbiota, and serum metabolites were evaluated. The results showed that the 3 TCM polysaccharides could increase the expression of antioxidant markers SOD, GSH, and CAT, and reduce the accumulation of MDA in the liver; the contents of IgA and IgM in serum were increased. Decreased the mRNA expression of TLR4, NFκB, TNF-α, IFN-γ, IL1β, IL6, and IL8, and increased the mRNA expression of anti-inflammatory factor IL5 in oviduct tissue. 16sRNA high-throughput sequencing revealed that the 3 TCM polysaccharides improved the intestinal flora disturbance caused by bacterial infection, increased the abundance of beneficial bacteria such as Bacteroides and Actinobacillus, and decreased the abundance of harmful bacteria such as Romboutsia, Turicibacter, and Streptococcus. Metabolomics showed that the 3 TCM polysaccharides could increase the content of metabolites such as 3-hydroxybutyric acid and isobutyl-L-carnitine, and these results could alleviate the further development of salpingitis. In conclusion, the present study has found that using TCM polysaccharides instead of antibiotics was a feasible way to prevent bacterial salpingitis in laying hens, which might make preventing this disease no longer an issue for breeding laying hens.


Skeletal muscle: length-dependent effects of potentiating agents.
The ability of vertebrae skeletal muscle to contract more vigorously than normal in the presence of potentiating agents depends on the initial length of a muscle cell. Other factors such as the intracellular calcium ion transient, temperature, chemical nature of the potentiating agent, and the ratio of intrinsic twitch to tetanic force influence the degree of contractile potentiation but cannot account for the length dependence. At least part of a muscle cell seems normally less than fully active during contractions not only at short lengths but also at optimal sarcomere lengths.


Acacia honey and chrysin reduce proliferation of melanoma cells through alterations in cell cycle progression.
Honey has long been used in medicine for different purposes. Only recently, however, its antioxidant property and preventive effects against different diseases, such as cancer, have been highlighted. Chrysin (5,7-dihydroxyflavone) is a natural flavone commonly found in acacia honey. It has previously been shown to be an anti-tumor agent. In this study, we investigated the antiproliferative role of honey or chrysin on human (A375) and murine (B16-F1) melanoma cell lines. The results of the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and the trypan blue exclusion test showed that both the tested compounds were able to induce an antiproliferative effect on melanoma cells in a dose- and time-dependent manner. Flow cytometry analysis indicated that cytotoxicity induced by honey or chrysin was mediated by G(0)/G(1) cell cycle arrest and induction of hyperploid progression. Our results suggest that the anti-proliferative effects of honey are due mainly to the presence of chrysin. Chrysin may therefore be considered a potential candidate for both cancer prevention and treatment. Further investigation is needed to validate the contribution of chrysin in tumor therapy in vivo.


A Turkish case of subcortical/subependymal heterotopia associated with corpus callosum dysgenesis, craniofacial dysmorphism, severe eye abnormalities, and growth-mental retardation.
The patient is a 12-year-old boy with a history of learning disability, growth retardation, and strabismus. Weight, height and head circumference were below the 3rd percentile. A café-au-lait spot, 1x1 cm a diameter, on the back region and pectus excavatum deformity were diagnosed. He had facial asymmetry, a broad nose, sparse eyebrows and eyelashes, a rudimentary frontal sinus, deviation of the nasal septum, and bilateral small maxillary bones. The left orbital fossa was also mildly rudimentary. On eye examination the movements of the left globe to the upward and lateral side were limited and internal strabismus was noted at this side. Visual acuity was 1/10, bilaterally. Bilateral choroid coloboma, glaucoma, vertical and horizontal nystagmus were diagnosed. Fundoscopic examination revealed bilateral optic atrophy and macular and paramacular granulation tissues on the left side. Intelligence quotient was 46. Electroencephalography revealed bilateral frontal slow-wave activity. Visual evoked potential revealed prolonged p100 wave latencies bilaterally. Magnetic resonance imaging of the brain demonstrated corpus callosum dysgenesis, bilateral subcortical heterotopia in the frontal lobes and subependymal heterotopia in the posterior horn of the left ventricle. Chromosomal analysis revealed a normal male karyotype, 46, XY. Although several cases of heterotopia in association with mental retardation, craniofacial dysmorphism, cerebral, and eye abnormalities have been described the combination of abnormalities diagnosed in our case has not previously been reported. We hypothesize that the combination of subcortical/subependymal heterotopia, corpus callosum dysgenesis, craniofacial dysmorphism, severe eye abnormalities, and growth-mental retardation may be a new syndrome.


Do clinicians follow a risk-sensitive model of capacity-determination? An experimental video survey.
The authors asked whether clinicians use a risk-sensitive model for decisional-capacity determinations; that is, whether a higher degree of capacity was required in higher-risk situations. The respondents were randomly assigned to view a videotaped "capacity" interview of a medication-randomized clinical trial scenario (N=52) or a neurosurgical clinical trial scenario (N=47). A significant scenario effect was mediated by the respondents' perception of scenario-specific risk. Respondents showed considerable disagreement within each scenario that was not explained by clinician-specific factors. Thus, clinicians, in fact, use the normative risk-sensitive model for capacity, but there remains considerable unexplained variability in their judgments.


Filamin A in somatostatin and dopamine receptor regulation in pituitary and the role of cAMP/PKA dependent phosphorylation.
Molecular mechanisms underlying resistance of pituitary tumors to somatostatin (SS) and dopamine (DA) analogues treatment are not completely understood. Resistance has been associated with defective expression of functional somatostatin and dopamine receptors SSTR2, SSTR5, and DRD2, respectively. Recently, a role of cytoskeleton protein filamin A (FLNA) in DRD2 and SSTR receptors expression and signaling in PRL- and GH-secreting tumors, respectively, has been demonstrated, first revealing a link between FLNA expression and responsiveness of pituitary tumors to pharmacological therapy. No molecular events underlying the reduction of FLNA levels in resistant tumors have been so far identified. FLNA can be phosphorylated by PKA on Ser2152, with increased FLNA resistance to cleavage by calpain and conformational changes affecting FLNA regions involved in SSTR2 and DRD2 binding and signal transduction. In this respect, the effect of cAMP/PKA pathway in the regulation of FLNA stability and/or function by modulating its phosphorylation status could assume particular importance in pituitary, where cAMP cascade plays a crucial role in pituitary cell functions and tumorigenesis. This review will discuss the role of FLNA in the regulation of the main GPCRs target of pharmacological treatment of pituitary tumors, that is, SSTR2 and DRD2, focusing on the effects of cAMP/PKA-mediated FLNA phosphorylation on FLNA biological functions.


Bacillus loiseleuriae sp. nov., isolated from rhizosphere soil from a loiseleuria plant.
A Gram-stain-positive, rod-shaped, endospore-forming, aerobic bacterium, designated strain FJAT-27997T, was isolated from the rhizosphere soil of a Loiseleuria plant collected from Sichuan province in China. Growth was observed aerobically between 20 and 35 °C (optimum 30 °C), between 0 and 3.0 % (w/v) NaCl (optimum at 0 %) concentration and pH in the range 6.0-9.0 (optimum at pH 7.0). The cell-wall peptidoglycan contained meso-diaminopimelic acid and the major isoprenoid quinone was menaquinone MK-7. The main fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C14 : 0, C16 : 0 and C14 : 0. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Phylogenetic analyses based on 16S rRNA gene sequences showed that isolate FJAT-27997T was a member of the genus Bacillus and was related most closely to Bacillus simplex DSM 1321T (97.95 % similarity), followed by Bacillushuizhouensis GSS03T (97.9 %). The average nucleotide identity value between strain FJAT-27997T and the most closely related species, B. simplex DSM 1321T, was 71.60 % (JSpecies), less than the previously proposed cut-off value of 96 % for differentiating species within the genus. The in silico DNA-DNA hybridization values between strain FJAT-27997T and its most closely related species were <70 %, again indicating they belong to different taxa. The main fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The novel strain could be differentiated from other known Bacillus species on the basis of several phenotypic characters and fatty acid profiles. This taxononomic/genomic study revealed that strain FJAT-27997T represents a novel Bacillus species, for which the name Bacillus loiseleuriae sp. nov. (type strain FJAT-27997T =CCTCC AB 2015285T=DSM 101776T) is proposed.


Mode and speed specificity of eccentric and concentric exercise training.
This research was supported by a Duke University Research Council Grant. The purpose of this study was to examine mode and speed specificity of strength training by comparing concentric and eccentric isokinetic exercise of the quadriceps. Forty-eight healthy men (mean age = 23.9 years) were randomly assigned to one of three groups: concentric training (C), eccentric training (E), or control (K). Average force (in Newtons) of 3 concentric and of 3 eccentric quadriceps contractions on the KIN-COM(R) dynamometer at 60, 120, and 180 degrees /sec was evaluated prior to and following a 6 week period during which only the C and E groups trained. Training sessions (3/week) included 4 submaximal and 1 maximal warm-up followed by 10 maximal effort isokinetic contractions of the quadriceps at 120 degrees /sec for each leg. Group C subjects trained concentrically only while Group E subjects trained eccentrically only. A t-test for independent means showed no significant right/left differences. ANOVA and Scheffe's F-tests were then used to assess the differences in training effects among the 3 groups for the left leg only. Results showed that although Group C increased slightly in both concentric and eccentric force at all speeds, the gains were significant only for concentric force at 180 degrees /sec. Group E showed significant gains (p < 0.05) in eccentric force at all speeds but not in concentric force. The K group had no significant change in concentric or eccentric force at any speed. We conclude that the eccentric mode of isokinetic exercise has highly specific strength training effects while the concentric mode has less specific training effects. In addition, speed of exercise does not appear to have specific training effects. J Orthop Sports Phys Ther 1989;11(2):70-75.


Humidity-Responsive Single-Nanoparticle-Layer Plasmonic Films.
2D materials possess many interesting properties, and have shown great application potentials. In this work, the development of humidity-responsive, 2D plasmonic nanostructures with switchable chromogenic properties upon wetting-dewetting transitions is reported. By exploiting DNA hybridization-directed anchoring of gold nanoparticles (AuNPs) on substrates, a series of single-nanoparticle-layer (SNL) plasmonic films is fabricated. Due to the collective plasmonic responses in SNL, these ultrathin 2D films display rapid and reversible red-blue color change upon the wetting-dewetting transition, suggesting that hydration-induced microscopic plasmonic coupling between AuNPs is replicated in the macroscopic, centimeter-scale films. It is also found that hydration finely tunes the electric field distribution between AuNPs in the SNL film, based on which responsive surface-enhanced Raman scattering substrates with spatially homogeneous hot spots are developed. Thus it is expected that DNA-mediated 2D SNL structures open new avenues for designing miniaturized plasmonic nanodevices with various applications.


Anxiolytic Effects of Royal Sun Medicinal Mushroom, Agaricus brasiliensis (Higher Basidiomycetes) on Ischemia-Induced Anxiety in Rats.
We investigated the anxiolytic effects Agaricus brasiliensis extract (AbSE) on ischemia-induced anxiety using the plus-maze test and the social interaction test. The animals were treated orally with AbSE (4, 8, and 10 mg/kg/d, respectively) for 30 d, followed by middle cerebral artery occlusion-induced cerebral ischemia. Levels of noradrenaline, dopamine, and serotonin in the cerebral cortex of rats, as well as oxidative stress and plasma corticosterone levels were analyzed, respectively. The rota-rod test was carried out to exclude any false positive results in experimental procedures related to anxiety disorders, and the catalepsy test was carried out to investigate whether AbSE induces catalepsy. Our results demonstrate that oral administration of AbSE presented anxiolytic-like effects in the elevated plus-maze test and the social interaction test. Furthermore, AbSE did not induce extrapyramidal symptoms in the catalepsy test. The mechanism underlying the anxiolytic effect of AbSE might be increased brain monoamine levels and plasma corticosterone levels and decreased oxidative stress in cerebral ischemia/reperfusion rats.


Associations between food groups, dietary patterns, and cardiorespiratory fitness in the Coronary Artery Risk Development in Young Adults study.
Few studies have investigated the association between overall diet and cardiorespiratory fitness (CRF). We aimed to investigate associations of food groups, a diet-quality score, and dietary patterns with CRF in black and white adults. We included 2632 participants aged 38-50 y who attended the year 20 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study and Coronary Artery Risk Development in Young Adults Fitness Study (CFS) conducted in 2005-2006. Diet was assessed by using a validated diet history. A dietary score and 2 types of patterns were included as follows: the a priori diet-quality score and meat and fruit-vegetable dietary patterns derived from principal components analysis. CRF was assessed by using a graded exercise treadmill test. Linear regression models regressed the treadmill duration on food groups and dietary scores and patterns overall and in race-sex subgroups. Grains (whole and refined), processed meats, and beverages (coffee, meal-replacement drinks, beer, and wine) were positively associated with the treadmill duration overall; whole fruit (not juices), organ meats, fried meats and fish, and soy and nondairy products were negatively associated. The a priori diet-quality score was positively associated with the duration overall and in all race-sex subgroups (P <0.05) except black men. The meat pattern was negatively associated with the duration in white men and white women only. The fruit-vegetable pattern was positively associated with duration in white women only. Overall, the a priori diet-quality score was positively associated with CRF in this cohort of black and white adults, whereas the meat dietary pattern was negatively associated only in whites. The CARDIA study and CFS were registered at clinicaltrials.gov as NCT00005130 and NCT00106457, respectively.