ELABELA/APJ Axis Prevents Diabetic Glomerular Endothelial Injury by Regulating AMPK/NLRP3 Pathway.
ELABELA (ELA), a recently discovered peptide, is highly expressed in adult kidneys and the endothelium system. It has been identified as a novel endogenous ligand for the apelin receptor (APJ). This study aims to investigate the role of ELA in diabetic glomerular endothelial pyroptosis and its underlying mechanism. Initially, a significant decrease in ELA mRNA levels was observed in the renal cortex of db/db mice and high glucose-treated glomerular endothelial cells (GECs). It was also found that ELA deficiency in ELA+/- mice significantly accelerated diabetic glomerular injury, as shown by exacerbated glomerular morphological damage, increased serum creatine and blood urea nitrogen, and elevated 24-h urinary albumin excretion. In addition, in vivo overexpression of ELA prevented diabetic glomerular injury, reduced von Willebrand factor expression, restored endothelial marker CD31 expression, and attenuated the production of adhesive molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1. Furthermore, in vitro studies confirmed that treatment with ELA inhibited GEC injury by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome, as indicated by blocking NLRP3 inflammasome formation, decreasing cleaved Caspase-1 production, and inhibiting interleukin-1β and interleukin-18 production. Moreover, in vitro experiments demonstrated that the protective effects of ELA in GECs during hyperglycemia were diminished by inhibiting adenosine monophosphate-activated protein kinase (AMPK) using Compound C or by APJ deficiency. Taken together, this study provides the first evidence that ELA treatment could prevent diabetic glomerular endothelial injury, which is partly mediated by the regulation of the AMPK/NLRP3 signaling pathway. Therefore, pharmacologically targeting ELA may serve as a novel therapeutic strategy for diabetic kidney disease.


Long-term unemployment among women in Sweden.
Vulnerability at long-term unemployment is discussed and the results of a study of the effects of job loss and long-term unemployment among Swedish women are presented. Psychological and physiological data for the unemployed were sampled repeatedly over a two year period. Some of the unemployed were subject to an intervention programme aiming at buffering for the possibly negative effects of unemployment. Health data from matched control groups of employed were gathered over the same period. The results indicate a strong negative stress reaction at the job loss period, followed by a gradual adaptation to the conditions of unemployment as measured by biochemical and physiological health indicators. However, a substantial proportion of the unemployed compared to the employed showed a lower degree of psychological well-being and more severe depressive reactions. Recommendations are given concerning further research approaches on long-term unemployment. Policy implications to reduce vulnerability at long-term unemployment are discussed.


The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes.
We report here that the bacterial lipopolysaccharide endotoxin induces human blood monocytes in a time- and dose-dependent manner to release prodigious amounts of prostaglandins with thromboxane A2, the major metabolite formed. Cells responded to as little as 1 ng/ml lipopolysaccharide to release prostaglandin E2 and thromboxane A2 with maximal stimulation at 10 micrograms/ml. Lipopolysaccharide was found to induce increased activity of cyclooxygenase enzyme without affecting the activities of phospholipase and thromboxane synthase or the formation of 5-lipoxygenase products (e.g. leukotriene B4). The glucocorticoid dexamethasone completely blocked the lipopolysaccharide-induced prostanoid release by inhibiting the activity of monocyte cyclooxygenase. Dexamethasone did not affect phospholipase and thromboxane synthase activities or leukotriene formation. Immunoprecipitation of [35S]methionine-labeled cyclooxygenase confirmed that the effect of lipopolysaccharide and dexamethasone on the monocyte prostanoid production could be attributed to an increase or decrease, respectively, in cellular cyclooxygenase de novo synthesis.


Bird diversity and density in south african forests.
Afromontane woodlands are fairly continuous in eastern Cape Province of southern Africa, but occur as increasingly smaller and more isolated patches towards Cape Town in the southwest. These habitat patches are similar in both vegetation structure and floristic composition. Although bird species numbers in the patches decline three-fold from east to west to 15 species at Table Mountain, total bird density remains roughly constant, and bird density per species increases threefold as species diversity declines by the same factor.A few species, especially frugivores, seedeators and nectarivores, may be restricted to the larger more easterly woodlands because their food resources are so restricted. Some species, perhaps the sallying flycatchers, may be more abundant in the western species-poor habitat patches because of the higher productivity in their food supplies, but evidence for this view is scant. Some guilds, most notably foliage insectivores and slow-searching omnivores, exhibit good density compensation, such that the elevated densities of species in impoversished woodlands are predictable from densities and overlaps in foraging ecology at the species-rich sites. The guild of foliage insectivores "warbler-types," declines in size serially from east to west at five sites: 5 spp-4-3-2-1; in this guild food resources are best matched amongst sites, and the predictions allowed, of the structure and composition of the increasingly smaller species subsets, are most detailed.


[Comparative histological and histochemical studies on the "spleen-ovary" in the rat (Lipschütz) following administration of FSH and spleen extract].
On the basis of the "Lipschuetz-ovary" model the rat ovary is cystically altered. -- In such an ovary the effect of a spleen extract (Solcosplen) and FSH (Anternon) were compared with histological and histochemical methods. -- With bothe the substances could be observed a diminution of the cystic degeneration.


Tumor-targeted delivery of siRNA to silence Sox2 gene expression enhances therapeutic response in hepatocellular carcinoma.
RNA interference (RNAi) is one of the most promising methods for the treatment of malignant tumors. However, developing an efficient biocompatible delivery vector for small interfering RNA (siRNA) remains a challenging issue. This study aimed to prepare a non-viral tumor-targeted carrier, named RGDfC-modified functionalized selenium nanoparticles (RGDfC-SeNPs). RGDfC-SeNPs were used to selectively deliver siSox2 to HepG2 liver cancer cells and tissues for the treatment of hepatocellular carcinoma (HCC). In the current study, RGDfC-SeNPs were successfully synthesized and characterized. It was shown that RGDfC-SeNPs could effectively load siSox2 to prepare an antitumor prodrug RGDfC-Se@siSox2. RGDfC-Se@siSox2 exhibited selective uptake in HepG2 liver cancer cells and LO2 normal liver cells, indicating RGDfC-SeNPs could effectively deliver siSox2 to HepG2 liver cancer cells. RGDfC-Se@siSox2 entered HepG2 cells via clathrin-mediated endocytosis by firstly encircling the cytoplasm and then releasing siSox2 in the lysosomes. RGDfC-Se@siSox2 could effectively silence Sox2 and inhibit the proliferation, migration and invasion of HepG2 cells. RGDfC-Se@siSox2 induced HepG2 cells apoptosis most likely via overproduction of reactive oxygen species and disruption of the mitochondrial membrane potentials. Most importantly, RGDfC-Se@siSox2 significantly inhibited the tumor growth in HepG2 tumor-bearing mice without obvious toxic side effects. These studies indicated that RGDfC-SeNPs may be an ideal gene carrier for delivering siSox2 to HepG2 cells and that RGDfC-Se@siSox2 may be a novel and highly specific gene-targeted prodrug therapy for HCC.


Mitigating hook effect in one-step quantitative sandwich lateral flow assay by timed conjugate release.
Sandwich lateral flow assay (LFA) is one of the most successfully commercialized paper-based biosensors, which offers a rapid, low-cost, one-step assay. Despite its advantages, conventional sandwich LFA is fundamentally limited by the high-dose "hook" effect-a phenomenon that occurs at very high analyte concentrations and results in false-negative results. In this paper, we present a novel strategy of automatic timed detection antibody release to mitigate the hook effect in sandwich LFA without additional manual steps. We introduced an intermediate pad treated with saturated sucrose solution to regulate the flow between the nitrocellulose membrane and the conjugate pad in order to delay the reaction between detection antibodies and analytes. Using C-reactive protein (CRP) as a representative analyte, we demonstrated that our strategy exhibited a range of detection 10 times wider than that of our conventional LFA, without sacrificing the limit of detection. Comparing to other published strategies, our work could offer a one-step, cost-effective approach that is closely unified with the benefits of the LFA.


HF progression among outpatients with HF in a community setting.
Incidence and prognostic impact of heart failure (HF) progression has been not well addressed. From 2009 until 2015, consecutive ambulatory HF patients were recruited. HF progression was defined by the presence of at least two of the following criteria: step up of ≥1 New York Heart Association (NYHA) class; decrease LVEF ≥ 10 points; association of diuretics or increase ≥ 50% of furosemide dosage, or HF hospitalization. 2528 met study criteria (mean age 76; 42% women). Of these, 48% had ischemic heart disease, 18% patients with LVEF ≤ 35%. During a median follow-up of 2.4 years, overall mortality was 31% (95% CI: 29%-33%), whereas rate of HF progression or death was 57% (95% CI: 55%-59%). The 4-year incidence of HF progression was 39% (95% CI: 37%-41%) whereas the competing mortality rate was 18% (95% CI: 16%-19%). Rates of HF progression and death were higher in HF patients with LVEF ≤ 35% vs >35% (HF progression: 42% vs 38%, p = 0.012; death as a competing risk: 22% vs 17%, p = 0.002). HF progression identified HF patients with a worse survival (HR = 3.16, 95% CI: 2.75-3.72). In cause-specific Cox models, age, previous HF hospitalization, chronic obstructive pulmonary disease, chronic kidney disease, anemia, sex, LVEF ≤ 35% emerged as prognostic factors of HF progression. Among outpatients with HF, at 4 years 39% presented a HF progression, while 18% died before any sign of HF progression. This trend was higher in patients with LVEF ≤ 35%. These findings may have implications for healthcare planning and resource allocation.


Schiff base crosslinked graphene/oxidized nanofibrillated cellulose/chitosan foam: An efficient strategy for selective removal of anionic dyes.
A versatile foam based on Schiff base crosslinking of oxidized nanofibrillated cellulose (ONFC) with amino modified graphene oxide (NGO) and chitosan (CS) was prepared for the efficacious selective removal of anionic dyes. (3-aminopropyl) triethoxysilane (APTES) was employed as a surface modifier to yield an amino modified graphene oxide (NGO). Meanwhile, ONFC was obtained via a periodate oxidation process to produce dialdehyde groups. Thus, the Schiff base crosslinking of ONFC with NGO and CS enabled to be readily accomplished, producing a versatile NGO/ONFC/CS foam. Systematical characterizations confirmed the successful covalent crosslinking and formation of NGO/ONFC/CS foams. Selective adsorption of Allura Red (AR) and orange G (OG) over cationic dye methylene blue (MB) by NGO/ONFC/CS was confirmed. It was found the maximum adsorption capacities of AR and OG at 303 K were 416.7 and 300.5 mg g-1, while it was 14.60 mg g-1 for MB. Thus, the new Schiff base crosslinked NGO/ONFC/CS paves the way for developing versatile graphene based foams in the applications of water treatment.


Alternatives to the grandmother hypothesis: a meta-analysis of the association between grandparental and grandchild survival in patrilineal populations.
We conducted a meta-analysis of 17 studies that tested for an association between grandparental survival and grandchild survival in patrilineal populations. Using two different methodologies, we found that the survival of the maternal grandmother and grandfather, but not the paternal grandmother and grandfather, was associated with decreased grandoffspring mortality. These results are consistent with the findings of psychological studies in developed countries (Coall and Hertwig Behavioral and Brain Sciences 33:1-59, 2010). When tested against the predictions of five hypotheses (confidence of paternity; grandmothering, kin proximity, grandparental senescence, and local resource competition), our meta-analysis results are most in line with the local resource competition hypothesis. In patrilineal and predominantly patrilocal societies, the grandparents who are most likely to live with the grandchildren have a less beneficial association than those who do not. We consider the extent to which these results may be influenced by the methodological limitations of the source studies, including the use of retrospective designs and inadequate controls for confounding variables such as wealth.


The nucleoside phosphatase method as a marker for the recognition of the autochthonous plexuses in blood vessel walls and the possible connection of the latter with acupuncture mechanisms.
The innervation of the blood vessels of the palatal mucosa of the frog is investigated histochemically. Besides vaso-motor nerves, fibers from the autochthonous plexuses also invest the vessels. Electron microscope studies of the latter show them to be non-nervous in structure contrary to previous belief. It is suggested they may influence vessels in a humoral manner and possibly play a part in acupuncture effector mechanisms. The electron micrographs are considered to reveal structure previously designated "terminal reticulum".


Utilization of seafood processing by-products: medicinal applications.
Large amount of underutilized by-products are generated from the seafood processing plants annually. Consequently, researches have been initiated to investigate those discarded materials and have identified a number of bioactive compounds including bioactive peptides, collagen and gelatin, oligosaccharides, fatty acids, enzymes, calcium, water-soluble minerals, and biopolymers. Bioactive peptides derived from fish by-products have shown various biological activities including antihypertensive and antioxidant activities and hence may be a potential material for biomedical and food industries. Collagen and gelatin are currently used in diverse fields including food, cosmetic, and biomedical industries. Other than that, they are promising drug carriers for the treatment of cancer. Many studies have reported that chitin, chitosan, and their derivatives possess biologically active polysaccharides and hence they are potential agents for many applications. Further, those compounds have also showed potential activities such as antioxidant, antibacterial, antiviral, antihypertensive, anticancer, etc. Hence, seafood by-products are valuable natural resources that show range of functionalities and hence potential materials for biomedical and nutraceutical industries.


Leveraging deep learning to identify calcification and colloid in thyroid nodules.
Both calcification and colloid in thyroid nodules are reflected as echogenic foci in ultrasound images. However, calcification and colloid have significantly different probabilities of malignancy. We explored the performance of a deep learning (DL) model in distinguishing the echogenic foci of thyroid nodules as calcification or colloid. We conducted a retrospective study using ultrasound image sets. The DL model was trained and tested on 30,388 images of 1127 nodules. All nodules were pathologically confirmed. The area under the receiver-operator characteristic curve (AUC) was employed as the primary evaluation index. The YoloV5 (You Only Look Once Version 5) transfer learning model for thyroid nodules based on DL detection showed that the average sensitivity, specificity, and accuracy of distinguishing echogenic foci in the test 1 group (n = 192) was 78.41%, 91.36%, and 77.81%, respectively. The average sensitivity, specificity, and accuracy of the three radiologists were 51.14%, 82.58%, and 61.29%, respectively. The average sensitivity, specificity, and accuracy of distinguishing small echogenic foci in the test 2 group (n = 58) was 70.17%, 77.14%, and 73.33%, respectively. Correspondingly, the average sensitivity, specificity, and accuracy of the radiologists were 57.69%, 63.29%, and 59.38%. The study demonstrated that DL performed far better than radiologists in distinguishing echogenic foci of thyroid nodules as calcifications or colloid.


Results of long segmental reconstruction of left anterior descending artery using left internal thoracic artery.
We performed long segmental reconstruction of the left anterior descending coronary artery (LAD) using the left internal thoracic artery (LITA) in patients with diffusely diseased coronary arteries. Our study investigated short- and long-term outcomes and angiographic results after complete revascularization using this technique. Between March 1995 and March 2001, 112 patients (mean age 63 years) underwent long segmental LAD reconstruction (≥2 cm) with or without endarterectomy using the LITA. Of these, 68 patients (61%) had a history of old myocardial infarction, 44 (39%) had undergone prior percutaneous coronary intervention, 39 (35%) had unstable angina, and 11 (10%) required preoperative intraaortic balloon pumping. The majority of patients (96%) underwent operation under cardiac arrest. All patients underwent a complete revascularization with long segmental LAD reconstruction using the LITA. The average length of arteriotomy was 3.7 cm, and 43 patients (38%) underwent extensive (≥4 cm) LAD reconstruction. Endarterectomy was performed in 37 patients (33%). The early mortality rate was 1.8% (2 of 112). Perioperative myocardial infarction in the LAD territory was 5.4%. The 5- and 10-year survival rates were 91% and 74%, respectively. Freedom from major adverse cardiac events at 10 years was 77%. Early angiography (n = 99) showed a 99% excellent patency rate of the LITA. Midterm (n = 61) and long-term (n = 23) follow-up angiography both showed 100% excellent patency rate of the LITA. Long segmental LAD reconstruction with or without endarterectomy using the LITA provided excellent long-term outcomes and acceptable early operative results, even in patients with diffusely diseased coronary arteries.


Effectiveness of simulation-based education on nursing students' professional knowledge, attitude and self-confidence in handling child abuse cases.
This study aimed to enhance nursing students' professional knowledge, attitudes and self-confidence in handling child abuse cases through a Child Abuse Simulation-Based Education (CASE). Given that nursing students seldom learn about child abuse case management in textbooks, simulation-based education could assist them in appropriately handling child abuse cases when they become nurses. Using a quasi-experimental design. 190 nurses enrolled in a night school in-service program at a Taiwanese university were recruited for this study. Ninety-four nurses in the experimental group took a simulation-based education on child abuse while 96 nurses in the contrast group took a general nursing course. The pretest and posttest professional knowledge, attitudes and self-confidence of both groups were analyzed using generalized estimating equations in SPSS V22 software. Following the introduction of the CASE course, the experimental group's posttest professional knowledge, attitudes and self-confidence in handling child abuse cases were higher than those of the contrast group (p < .001). Further analysis showed that professional knowledge increased with tenure, positivity in attitude increased with clinical ladder rating and male nurses were more confident than female nurses when handling child abuse cases. Based on the results, this study proposes recommendations for implementing child abuse simulation-based education for new nurses and those undergoing continuing education.


Microglial responses to dopamine in a cell culture model of Parkinson's disease.
Activated microglia appear to selectively attack dopamine (DA) neurons in the Parkinson's disease (PD) substantia nigra. We investigated potential mechanisms using culture models. As targets, human SH-SY5Y cells were left undifferentiated (UNDIFF) or were differentiated with retinoic acid (RA) or RA plus brain-derived neurotrophic factor (RA/BDNF). RA/BDNF-treated cells were immunoreactive for tyrosine hydroxylase and the DA transporter, took up exogenous DA, and released DA after K(+) stimulation. Undifferentiated and RA-treated cells lacked these characteristics of a DA phenotype. Co-culture of target cells with human elderly microglia resulted in elevated toxicity in DA phenotype (RA/BDNF) cells. Lipopolysaccharide (LPS) plus K(+)-stimulated DA release enhanced toxicity by 500-fold. DA induced microglial chemotaxis in Boyden chambers. Spiperone inhibited this effect. Cultured human elderly microglia expressed mRNAs for D1-D4 but not D5 DA receptors. The microglia, as well as PD microglia in situ, were also immunoreactive for D1-D4 but not D5 DA receptors. These findings demonstrate that activated microglia express DA receptors, and suggest that this mechanism may play a role in the selective vulnerability of DA neurons in PD.


Interval between simulated deep inspirations on the dynamics of airway smooth muscle contraction in guinea pig bronchi.
A certain amount of time is required to achieve a maximal contraction from airway smooth muscle (ASM) and stretches of substantial magnitude, such as the ones imparted by deep inspirations (DIs), interfere with contraction. The duration of ASM contraction without interference may thus affect its shortening, its mechanical response to DIs and the overall toll it exerts on the respiratory system. In this study, the effect of changing the interval between DIs on the dynamics of ASM was examined in vitro. Isolated bronchi derived from guinea pigs were held isotonically and stimulated to both contract and relax, in a randomized order, in response to 10-5 M of methacholine and 10-6 M of isoproterenol, respectively. Interference to ASM was inflicted after 2, 5, 10 and 30 min in a randomized order, by imposing a stretch that simulated a DI. The shortening before the stretch, the stiffness before and during the stretch, the post-stretch elongation of ASM and the ensuing re-shortening were measured. These experiments were also performed in the presence of simulated tidal breathing achieved through force fluctuations. The results demonstrate that, with or without force fluctuations, increasing the interval between simulated DIs increased shortening and post-stretch elongation, but not stiffness and re-shortening. These time-dependent effects were not observed when ASM was held in the relaxed state. These findings may help understand to which extent ASM shortening and the regulatory effect of DI are affected by changing the interval between DIs. The potential consequences of these findings on airway narrowing are also discussed.


Effect of direct infusion of antifungal agent on invasive pulmonary aspergillosis in a patient with acute leukemia.
Invasive pulmonary aspergillosis is a serious problem in the treatment of patients with acute leukemia. A 52-year-old woman with acute myeloid leukemia developed invasive pulmonary aspergillosis during remission induction chemotherapy. Initially, we treated her with a continuous intravenous drip infusion of amphotericin B, together with itraconazole, given orally. A peripheral crescentic cavity formed in the fungal lesion after the number of neutrophils recovered, and we therefore performed a direct infusion of miconazole into the cavity transbronchially. The lung lesion resolved dramatically shortly after this treatment. In this patient, the transbronchial infusion of an antifungal agent seemed to have been very useful for bringing about prompt resolution of the fungal lesion.


Melatonin reduces inflammatory injury through inhibiting NF-kappaB activation in rats with colitis.
Proinflammatory mediators are important in the pathogenesis of IBD, which are regulated by activation of NF-kappaB. The aim of this study was to investigate whether melatonin reduces inflammatory injury and inhibits proinflammatory molecule and NF-kappaB in rats with colitis. Rat colitis model was established by TNBS enema. NF-kappaB p65, TNF-alpha, ICAM-1, and IkappaBalpha in colon tissue were examined by immunohistochemistry, EMSA, RT-PCR, and Western blot analysis. Expression of proinflammatory molecule and activation of NF-kappaB were upregulated and IkappaB level decreased in rats with colitis. Melatonin reduces colonic inflammatory injury through downregulating proinflammatory molecule mediated by NF-kappaB inhibition and blockade of IkappaBalpha degradation.


Comparative effects of verapamil and nitroprusside on left ventricular function in patients with hypertension.
The effects of verapamil were compared with those of nitroprusside at matched mean arterial pressures and heart rates in 10 symptomatic hypertensive patients during cardiac catheterization. Simultaneous radionuclide angiography and micromanometer pressure measurements were obtained to assess left ventricular pressure-volume relations. Compared with control conditions, verapamil increased left ventricular end-diastolic volume index from 57 +/- 16 to 70 +/- 28 ml/m2 (p = 0.05) without a significant increase in left ventricular end-diastolic pressure (from 10 +/- 4 to 13 +/- 6 mm Hg). Despite a downward and rightward shift in the end-systolic pressure-volume relation indicating negative inotropic effects, ejection fraction did not decrease significantly (from 52 +/- 9% to 46 +/- 9%); cardiac index and stroke volume index remained unchanged. The change in stroke volume index with verapamil was directly related to the magnitude of change in end-diastolic volume index (r = 0.82, p less than 0.005), suggesting that the increase in end-diastolic volume did not arise purely from negative inotropic effects. Systemic vascular resistance index decreased from 42 +/- 8 to 34 +/- 7 mm Hg.min.m2/liter (p less than 0.05). In contrast, nitroprusside decreased left ventricular end-diastolic volume index from 57 +/- 16 to 41 +/- 10 ml/m2 (p less than 0.05), cardiac index from 3.2 +/- 0.7 to 2.8 +/- 0.6 liters/min per m2 (p less than 0.05) and stroke volume index from 28 +/- 6 to 24 +/- 5 ml/m2 (p less than 0.01), with no change in systemic vascular resistance index (40 +/- 10 mm Hg.min.m2).(ABSTRACT TRUNCATED AT 250 WORDS)


Leptomeningeal infiltration in rat models for human acute myelocytic and lymphocytic leukemia.
With respect to human leukemia, scarce data exist suggesting a difference in the leptomeningeal infiltration pattern between acute myelocytic leukemia (AML) and acute lymphocytic leukemia (ALL). In the present paper, the growth pattern of intrathecally inoculated AML and ALL in rat models is studied. It was observed that the leptomeningeal infiltration in ALL is more pronounced than in AML. In AML, no infiltration of the pia mater, ventricles or Virchow-Robin spaces were seen, in contrast to ALL, where these structures were infiltrated frequently. Both models were mimicking the pattern of leptomeningeal infiltration observed in the respective human leukemias. These animal models provide reproducible systems in which the determinants of metastatic capacity and their therapeutic implications for ALL and AML can be studied.


Serotonin and the neuropeptide PDF initiate and extend opposing behavioral states in C. elegans.
Foraging animals have distinct exploration and exploitation behaviors that are organized into discrete behavioral states. Here, we characterize a neuromodulatory circuit that generates long-lasting roaming and dwelling states in Caenorhabditis elegans. We find that two opposing neuromodulators, serotonin and the neuropeptide pigment dispersing factor (PDF), each initiate and extend one behavioral state. Serotonin promotes dwelling states through the MOD-1 serotonin-gated chloride channel. The spontaneous activity of serotonergic neurons correlates with dwelling behavior, and optogenetic modulation of the critical MOD-1-expressing targets induces prolonged dwelling states. PDF promotes roaming states through a Gαs-coupled PDF receptor; optogenetic activation of cAMP production in PDF receptor-expressing cells induces prolonged roaming states. The neurons that produce and respond to each neuromodulator form a distributed circuit orthogonal to the classical wiring diagram, with several essential neurons that express each molecule. The slow temporal dynamics of this neuromodulatory circuit supplement fast motor circuits to organize long-lasting behavioral states.


Prediction of lattice energy of benzene crystals: A robust theoretical approach.
We present an inexpensive and robust theoretical approach based on the fragment molecular orbital methodology and the spin-ratio scaled second-order Møller-Plesset perturbation theory to predict the lattice energy of benzene crystals within 2 kJ⋅mol-1 . Inspired by the Harrison method to estimate the Madelung constant, the proposed approach calculates the lattice energy as a sum of two- and three-body interaction energies between a reference molecule and the surrounding molecules arranged in a sphere. The lattice energy converges rapidly at a radius of 13 Å. Adding the corrections to account for a higher correlated level of theory and basis set superposition for the Hartree Fock (HF) level produced a lattice energy of -57.5 kJ⋅mol-1 for the benzene crystal structure at 138 K. This estimate is within 1.6 kJ⋅mol-1 off the best theoretical prediction of -55.9 kJ⋅mol-1 . We applied this approach to calculate lattice energies of the crystal structures of phase I and phase II-polymorphs of benzene-observed at a higher temperature of 295 K. The stability of these polymorphs was correctly predicted, with phase II being energetically preferred by 3.7 kJ⋅mol-1 over phase I. The proposed approach gives a tremendous potential to predict stability of other molecular crystal polymorphs.


Genetic and morphological evidence for substantial hidden biodiversity in a freshwater crayfish species complex.
North America is a center of biodiversity for freshwater crayfish, with >300 described species, mostly in the family Cambaridae. However, the phylogenetic and phylogeographic relationships among these taxa are poorly understood, despite their ubiquitous occurrence in North American freshwater habitats. Here, we target the geographically widespread Orconectesvirilis and its sister taxa for genetic and morphological investigation. We used sequence data from two mitochondrial genes (16S rRNA and cytochrome oxidase I) and from one nuclear gene (glyceraldehyde-3-phosphate dehydrogenase), as well as morphological data from the male gonopod, to gain insights into phylogenetic relationships among individuals collected in the northeastern United States, where this taxon is considered to be invasive, and from Kansas. Our data reveal evidence for three cryptic species in our collections, in addition to O.virilis sensu stricto; all four clades are separated by both mitochondrial and nuclear sequence data. In addition, two of the newly discovered species, O.sp. nov. A and O.sp. nov. B, are distinguishable from O.virilis by significant differences in gonopod morphology (no data on gonopod morphology were available for O.sp. nov. C). O.sp. nov. A was collected at numerous sites in Massachusetts; additional sampling is required to determine if this species is native to New England. Two other taxa, O.sp. nov. B and O.sp. nov. C, were both collected from sites in eastern Kansas, and historically have probably been considered to be O.nais. In summary, this investigation indicates that this species complex may harbor a great deal of unknown biodiversity over the rest of its described range, and suggests that further attention to the phylogenetics and phylogeography of North American crayfishes may yield interesting insights into the evolution of biodiversity.


Peripheral blood lymphocyte subpopulations in multiple myeloma.
Antisera raised against idiotypic determinants of myeloma proteins and macroglobulins have been used to differentiate peripheral blood lymphocytes populations from individual patients. I.D.-positive lymphocytes not resembling plasma cells have been regularly found in peripheral blood in these diseases. This lymphocyte population is heterogeneous with respect to non-tumor-specific surface markers, such as SRBC-, Fc- and C-receptors. Tumor specific idiotypic determinants will thus allow a more correct recognition of the total tumor cell compartment in these diseases.


[Transcatheter arterial embolization of renal carcinoma with absolute ethanol].
To study transcatheter arterial embolization (TAE) of renal carcinoma using absolute ethanol so as to reduce bleeding for a higher resection rate, as a palliative treatment for advanced renal carcinoma. Using Seldinger method, we treated 25 cases of renal carcinoma with transcatheter arterial embolization. The average bleeding of 25 cases during nephrectomy was 210ml after TAE. There was no mortality and serious complication. But there was pain and fever in most cases. TAE with absolute ethanol is an effective, safe and easy procedure. It could be used as an adjuvant therapy for renal carcinoma.


Mechanism of the depressor response to dopamine in the rat treated with phenoxybenzamine.
Alterations of hypotensive responses to dopamine by antagonists were characterized in alpha-blocked, anaesthetized rats. Responses were not affected by d-propranolol (0.1 mg/kg) whereas d,1-propranolol (0.1 mg/kg) or haloperidol (1.0 mg/kg) attenuated them; higher doses of inhibitors (1.0 mg/kg; 5.0 mg/kg, respectively) failed to produce a higher inhibition, but combinations of low doses abolished the depressor responses. In adrenalectomized rats, hypotensive responses decreased; haloperidol always attenuated the responses while d,1-propranolol became ineffective. Dopamine produced an enhancement of plasma adrenaline and noradrenaline levels, which was decreased by d,1-propranolol and increased by haloperidol. The data suggest that in rats the depressor component of dopamine is due to activation of both dopaminergic and beta-adrenoceptors. The beta component appears to be due to the release of adrenaline. The results also support the concept of the existence in sympathetic nerve endings and adrenal glands of stimulatory beta-adrenergic and inhibitory dopaminergic prejunctional receptors.


Cross-national comparative study of orphan drug policies in Saudi Arabia, the United States, and the European Union.
Rare diseases are chronic, serious, and life-threatening conditions that have not received sufficient attention from drug developers due to their rarity. Policies have been implemented to encourage research and incentivize the development of orphan drugs. However, the implementation of these policies has been inconsistent worldwide. The primary aim of this study was to compare orphan drug policies in the United States, Europe, and Saudi Arabia (SA) and assess their impact on the number of approved indications. Lists of all drugs granted orphan designations and authorized for marketing in the United States, European Union, and SA were extracted using orphan drug lists available in regulatory body databases. The availability of these drugs, regarding their approval for orphan indication and designation, was assessed and classified using Anatomical Therapeutic Chemical codes. A total of 792 orphan drug designations with at least one authorized indication were identified in this study. Of these, 92% were designated by the Food and Drug Administration (FDA), and 27% were designated by the European Medicine Agency (EMA). The FDA, EMA, and Saudi Food and Drug Authority approved 753, 435, and 253 orphan drugs, respectively. Fewer orphan drug approvals were found in SA than in the United States and Europe. This highlights the need to focus on rare diseases and orphan drugs and for policies to be created in SA to attract pharmaceutical markets and fulfill unmet orphan drug approval needs.


Optimal foraging: food patch depletion by ruddy ducks.
I studied the foraging behavior of ruddy ducks (Oxyura jamaicensis) feeding on patchily distributed prey in a large (5-m long, 2-m wide, and up to 2-m deep) aquarium. The substrate consisted of a 4x4 array of wooden trays (1.0-m long, 0.5-m wide, and 0.1-m deep) which contained 6 cm of sand. Any tray could be removed from the aquarium and "loaded" with a known number of prey. One bird foraged in the aquarium at a time; thus, by removing a food tray after a trial ended and counting the remaining prey, I calculated the number of prey consumed by the bird. I designed several experiments to determine if ruddy ducks abandoned a food patch in a manner consistent with the predictions of a simple, deterministic, patch depletion model. This model is based on the premise that a predator should maximize its rate of net energy intake while foraging. To accomplish this, a predator should only remain in a food patch as long as its rate of energy intake from that patch exceeds the average rate of intake from the environment. In the majority of comparisons, the number of food items consumed by the ruddy ducks in these experiments was consistent with the predictions of the foraging model. When the birds did not forage as predicted by the model, they stayed in the patch longer and consumed more prey than predicted by the model. An examination of the relation between rate of net energy intake and time spent foraging in the food patch indicated that by staying in a patch longer than predicted, the ruddy ducks experienced only a small deviation from maximum rate of net energy intake. These results provided quantitative support for the prediction that ruddy ducks maximize their rate of net energy intake while foraging.


Chemically-induced unscheduled DNA synthesis in cultures of adult human epidermal keratinocytes.
Skin is a major target organ for many experimental carcinogens that exist in our environment and the majority of previous carcinogenicity studies have utilised animal derived models. In view of the fact, that many of these environmental chemicals exhibit species- and tissue-specific metabolism, a human skin tissue derived model would be a distinct advantage. Squamous epithelial carcinoma is a predominant form of skin cancer in man and, in theory, human epidermal keratinocytes present an appropriate target cell to employ as an in vitro system to study epidermal carcinogenesis. This report demonstrates the valuable potential of human keratinocyte cultures as a suitable model for mechanistic studies on factors which may influence DNA damage and, hence, the subsequent development of cancer in human epidermis. Keratinocytes were serially cultivated from adult human skin samples and maintained in culture for at least 3 passages. Tertiary cultures, isolated from 3 separate individuals, were exposed to the direct-acting experimental carcinogen, methyl methanesulphonate (CAS No. 66-27-3), and benzo[a]pyrene (CAS No. 50-32-8), which requires metabolic activation. DNA repair was assessed by a quantitative autoradiographic technique. Methyl methanesulphonate and benzo[a]pyrene both elicited a dose-related increase in unscheduled DNA synthesis in cultures prepared from each individual. Inter-individual variation in the response was observed for each chemical, but this was greater in the case of benzo[a]pyrene, which indicates inter-individual variation in both xenobiotic metabolism activity and DNA repair capacity.


Actin in the inner ear: the remarkable structure of the stereocilium.
The actin filament bundle in the stereocilium of the cochlear hair cell has liquid transverse order, but paracrystalline axial order. A single bonding rule, which determines how a cross bridging protein links neighbouring filaments, accounts for this unusual structure. Such liquid order is possible for bundles of other filamentous proteins.


The effect of various adjuvants on the humoral immune response of sheep and cattle to soluble and membrane midgut antigens of Boophilus microplus.
Sheep and cattle were immunized with soluble and membrane midgut antigens of the cattle tick, Boophilus microplus in association with various adjuvants, and antibody levels to soluble and membrane midgut extracts were measured by enzyme-linked immunosorbent assay (ELISA). The adjuvants used were Quil A, Freund's incomplete adjuvant (FIA) and aluminium hydroxide (A1(OH)3). Significant antibody levels to midgut membrane antigen (GM) were not detected in the sera of sheep immunized with GM plus A1(OH)3. However, membrane and soluble midgut antigens combined with Quil A generated significantly higher levels of antibodies in sheep than these antigens emulsified in FIA (P < 0.05). In cattle, although soluble midgut antigen (GS) plus Quil A induced significantly higher levels of antibodies compared with GS in FIA (P < 0.05), neither preparation provided significant protective immunity against challenge with B. microplus (46% and 22%, respectively). A soluble form of membrane midgut antigen extracted by low ionic strength buffer (LI-GM) when combined with Quil A provided 83% and 87% protection against challenge with B. microplus in two separate experiments. Quil A was clearly superior to FIA and A1(OH)3 as an adjuvant for these tick antigens.


The effectiveness of the national hepatitis B vaccination program 25 years after its introduction in Iran: a historical cohort study.
Hepatitis B virus (HBV) is responsible for one of the most common human viral infections. An estimated 257 million people are living with chronic HBV infection worldwide, and mortality has reached 900,000 deaths in recent years. In 2001, the World Health Organization reported a prevalence of chronic hepatitis B infection in Iran between 2-7%. To assess the effect of the national HBV mass vaccination program after 25 years. A retrospective cohort study was conducted in vaccinated and unvaccinated people according to the year of birth. Blood samples were obtained from each enrolled person and data about demographic variables, and medical and vaccination history were collected using a standardized questionnaire. Persons were considered uninfected if they were negative for both HBsAg and anti-HBc. Also, Vaccine effectiveness was measured by calculating the risk of disease among vaccinated and unvaccinated persons and defining the percentage risk reduction of infection in the vaccinated group. A total of 2720 persons were interviewed. The rate of HBV breakthrough infection among the vaccinated group was significantly lower than in unvaccinated group. One hundred ninety-four cases with positive HBV markers of infection were identified. The risk ratio of HBV infection was 0.71, 95% CI: 0.54-0.94 (vaccinated/unvaccinated). The estimated vaccination effectiveness against Hepatitis B infection was 29% (95% CI: 6%-46%). Iran has successfully combined hepatitis B vaccination into regular immunization programs. The WHO goal of reducing HBsAg prevalence to an equivalent of 1% by 2020 has been reached. With respect to vaccination effectiveness and low prevalence of the disease in the country, catch-up hepatitis B vaccination programs for adolescents can guarantee the immunity of the population.


[Nasopharyngeal angiofibroma with intracranial extension: situating the chemotherapy-radiotherapy association].
Nasopharyngeal angiofibroma is a locally aggressive, although histologically benign, vascular neoplasm. This neoplasm accounts for 0.05% of head and neck tumours and affects almost exclusively male adolescents. Surgery is considered as the primary treatment of nasopharyngeal angiofibroma. Other treatment modalities such as radiotherapy and chemotherapy are still recommended for intracranial extension involving the cavernous sinus or the internal carotid artery. We report a rare case of nasopharyngeal angiofibroma, further complicated with a Kennedy syndrome in a 34 year-old women. The treatment consisted in a chemotherapy (adriamycine, decarbazine) followed by radiotherapy. We discuss the relevance and outcome of the association chemotherapy-radiotherapy in the treatment of nasopharyngeal angiofibromas with a consistent intracranial extension (stage III B of Arch Otolaryngol Head Neck Surg 122 (2003) 122-129).


Breast Cancer in Women Aged 80 Years or Older: An Analysis of Treatment Patterns and Disease Outcomes.
No clear standard treatment guidelines exist for older women with breast cancer. In this study we aimed to examine the practice patterns and treatment outcomes of women ≥80 years old with invasive breast cancer. A retrospective chart review at a single academic institution was performed of 124 women diagnosed with stage I to III invasive breast cancer aged ≥80 years between 2005 and 2014. Median age of diagnosis was 84 years. Fifty-nine of the cancers (48%) were detected using mammography. One hundred twelve patients (90%) underwent surgery. There was no difference in comorbidities between the surgical and nonsurgical group (P = .800). In multivariate analysis, age was predictive of receiving surgery (P < .001). Overall survival probability was higher for those who received hormonal therapy (P = .002), radiation therapy (P = .041), and those with lower-stage tumors (P = .018). Surgery was not predictive of survival. It is important to consider comorbidities, complications and, longevity when determining whether elderly women diagnosed with breast cancer benefit from surgery.


Radiological evidence of subcutaneous emphysema leading to a diagnosis of retroperitoneal perforated diverticulum.
This case report outlines the investigation and management of a young patient presenting with left iliac fossa pain and sepsis. A CT was performed which was initially reported as not showing a perforation, however closer analysis provided evidence of subcutaneous emphysema in the anterior abdominal wall. This evidence justified urgent operative intervention. We review the evidence with regard to this presentation. A previously fit 24-year-old male presented with left iliac fossa pain and features of sepsis. A CT provided subtle but distinctive evidence of retroperitoneal perforation secondary to diverticulitis, in the form of surgical emphysema in the anterior abdominal wall. In view of this, urgent operation was considered justified on suspicion of visceral perforation. A diverticular perforation was confirmed intra-operatively, and a sigmoid colectomy with primary anastomosis was performed, together with a covering ileostomy. The patient made a good post-operative recovery. Diverticular disease and its complications are becoming more common in a younger age group, in whom perforation may present late or may not be suspected. In this context special attention must be paid to any radiological evidence of perforation. Surgical emphysema in the abdominal wall is an indicator of retroperitoneal perforation, and its presence should be excluded before the possibility of perforation is dismissed. This may be of especial value in younger age groups amongst whom perforation may be less clinically obvious.


Supramolecular Assemblies of Glycopeptides Enhance Gap Junction Maturation of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes via Inducing Spheroids Formation to Optimize Cardiac Repair.
Stem cell-based therapies have demonstrated significant potential for use in heart regeneration. An effective paradigm for heart repair in rodent and large animal models is the transplantation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Despite this, the functional and phenotypical immaturity of 2D-cultured hiPSC-CMs, particularly their low electrical integration, poses a caveat for clinical translation. In this study, a supramolecular assembly of a glycopeptide containing a cell adhesion motif-RGD, and saccharide-glucose (Bio-Gluc-RGD) is designed to enable the 3D spheroid formation of hiPSC-CMs, promoting cell-cell and cell-matrix interactions that occur during spontaneous morphogenesis. HiPSC-CMs in spheroids are prone to be phenotypically mature and developed robust gap junctions via activation of the integrin/ILK/p-AKT/Gata4 pathway. Monodispersed hiPSC-CMs encapsulated in the Bio-Gluc-RGD hydrogel are more likely to form aggregates and, therefore, survive in the infarcted myocardium of mice, accompanied by more robust gap junction formation in the transplanted cells, and hiPSC-CMs delivered with the hydrogels also displayed angiogenic effect and anti-apoptosis capacity in the peri-infarct area, enhancing their overall therapeutic efficacy in myocardial infarction. Collectively, the findings illustrate a novel concept for modulating hiPSC-CM maturation by spheroid induction, which has the potential for post-MI heart regeneration.


Combined effect of acute salt and nitrogen stress on the physiology of lichen symbiotic partners.
Nitrogen pollution and excessive salinity are commonly regarded as one of the major environmental concerns in recent decades in many urban environments. Although in urban areas lichens are exposed to both salt and nitrogen stress, no studies have been conducted to date on the simultaneous impact and interaction of these factors on lichen physiology. The aim was to determine the effect of various combinations of NaCl and NH4NO3 doses on the physiology of epigeic lichen Cladonia rei. We also aimed to compare the response of lichens collected from polluted and unpolluted sites to verify whether lichens exposed to different levels of environmental stress in their native environment will react differently. The combined salt-nitrogen treatment caused significant disturbances in the integrity of cell membranes and chlorophyll fluorescence parameters. The most detrimental effect concerned the loss of cell membrane integrity, which suggests that this parameter can serve as a relevant indicator of acute salt-nitrogen stress incidents. Salt stress decreased the photosynthetic efficiency 1 h after exposure, but after 72 h, the FV/FM returned to the level characteristic of healthy lichens in experimental groups without and with small doses of ammonium nitrate. In contrast, recovery was not possible in combination with high nitrogen doses. This indicates that exposure to short-term salt stress in a nitrogen-poor environment only causes a temporary reduction in photosynthetic efficiency, but in urban eutrophic environments may have more serious consequences. The weakened physiological condition of the mycobiont manifested by an increased level of cell membrane damage and a persistent decrease in the photosynthetic efficiency of the photobiont in lichens growing along the roads may indicate an excess of nitrogen in the environment, enhanced by the effect of salt. Lichens collected from a heavy-metal-polluted habitat responded more strongly than those from an unpolluted habitat suggesting that in lichens previously affected by certain harmful factors, exposure to another stress factor may lead to greater disturbances. This is of particular importance for lichens inhabiting the vicinity of roads, since they are also under the influence of other pollutants emitted by road traffic.


Effects of dietary Scutellaria baicalensis extract on growth performance, immune-related genes expression, and resistance against Vibrio parahaemolyticus in white shrimp (Litopenaeus vannamei).
In this study dietary Scutellaria baicalensis extract (SBE) was used to improve the shrimps' immune response and its resistance to Vibrio parahaemolyticus. SBE obtained by solid-liquid extraction (SLE) has shown stronger antibacterial activity against V. parahaemolyticus compared to extracts obtained through the pressurized liquid extraction (PLE) method. A stronger immune response, such as the production of reactive oxygen species and the induction of expression of immune genes in hemocytes was seen in the SBE (SLE) treated group in vitro. SBE (SLE) had better immune stimulation effects and bactericidal activity than SBE (PLE) and therefore was chosen for in vivo feeding trial. The group fed with 1% SBE showed a better growth performance after 2 weeks of the feeding trial, but the growth-promoting effects did not last until the end of the trial at week four. Higher SBE intake reduced shrimp resistance to V. parahaemolyticus on week two but showed better resistance than the control group on the fourth week. Gene expression assays were used to investigate contradictory responses of the SBE-fed groups to V. parahaemolyticus at different times. Most of the genes examined in the selected tissues were not significantly changed, suggesting that the higher mortality of shrimp fed with high dose of SBE was not due to suppression of immune-related genes at earlier time point. Collectively, the bioactivity of SBE is influenced by the extraction conditions. Higher dietary doses of SBE (1% and 5%) improved the resistance of the white shrimp to V. parahaemolyticus after a longer feeding period (week four), but caution should be taken when applying SBE in the feed since a vulnerable status (week two) was seen during the feeding trial.


Association among peripatellar fat pad edema and related patellofemoral maltracking parameters: a case-control magnetic resonance imaging study.
The peripatellar fat pads are critical for protective cushioning during movement, and their endocrine function has been shown to affect osteoarthritis. Magnetic resonance imaging (MRI) is frequently used to visualize edema of the peripatellar fat pads due to injury. In this study, we aimed to assess the relationship between peripatellar fat pad edema and patellofemoral maltracking MRI parameters and investigate the association among cases of peripatellar fat pad edema. Age- and sex-matched peripatellar fat pad edema cases were identified and divided into superolateral Hoffa, quadriceps, and prefemoral groups. Images were assessed according to tibial tuberosity lateralization, trochlear dysplasia, patellar alta, patellar tilt, and bisect offset. McNemar's test or paired t-tests and Spearman's correlation were used for statistical analysis. Interobserver agreement was assessed with the intraclass correlation coefficient. Of 1210 MRI scans, 50, 68, and 42 cases were in the superolateral Hoffa, quadriceps, and prefemoral groups, respectively. Subjects with superolateral Hoffa fat pad edema had a lower lateral trochlear inclination (p = 0.028), higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.021) ratios, and lower patellotrochlear index (p < 0.001) than controls. The prefemoral group had a lower lateral trochlear inclination (p = 0.014) and higher Insall-Salvati (p < 0.001) and modified Insall-Salvati (p = 0.004) ratios compared with the control group. In contrast, the patellotrochlear index (p = 0.001) was lower. Mean patellar tilt angle (p = 0.019) and mean bisect offset (p = 0.005) were significantly different between cases and controls. The quadriceps group showed no association. Superolateral Hoffa was positively correlated with prefemoral (p < 0.001, r = 0.408) and negatively correlated with quadriceps (p < 0.001, r = -0.500) fat pad edema. Superolateral Hoffa and prefemoral fat pad edemas were associated with patellar maltracking parameters. Quadriceps fat pad edema and maltracking parameters were not associated. Superolateral Hoffa fat pad edema was positively correlated with prefemoral and negatively correlated with quadriceps fat pad edema.


Risks of surgery for upper gastrointestinal hemorrhage: 1972 versus 1982.
A retrospective comparison was undertaken to determine if the risks of undergoing surgery for nonvariceal upper gastrointestinal hemorrhage had changed between 1972 and 1982. In 1982, patients were on the average 9 years older, there was a significant decrease in bleeding from duodenal ulcers compared with 1972 data, gastric ulcer rates remained unchanged, and diffuse gastritis occurred more frequently in 1982. Mortality and morbidity rates showed no significant differences; however, the patient population did change with the emergence of older patients, in whom bleeding developed after hospitalization for other reasons. These patients comprised 30 percent of the 1982 study population. If further improvements in surgical treatment of upper gastrointestinal hemorrhage are to occur, these patients must be identified and aggressively managed.


Matrine promotes liver cancer cell apoptosis by inhibiting mitophagy and PINK1/Parkin pathways.
Matrine is a natural alkaloid isolated from the root and stem of the legume plant Sophora. Its anti-proliferative and pro-apoptotic effects on several types of cancer have been well-documented. However, the role of matrine in regulating mitochondrial homeostasis, particularly mitophagy in liver cancer apoptosis, remains uncertain. The aim of our study was to explore whether matrine promotes liver cancer cell apoptosis by modifying mitophagy. HepG2 cells were used in the study and treated with different doses of matrine. Cell viability and apoptosis were determined by MTT assay, TUNEL staining, western blotting, and LDH release assay. Mitophagy was monitored by immunofluorescence assay and western blotting. Mitochondrial function was assessed by immunofluorescence assay, ELISA, and western blotting. The results of our study indicated that matrine treatment dose-dependently reduced cell viability and increased the apoptotic rate of HepG2 cells. Functional studies demonstrated that matrine treatment induced mitochondrial dysfunction and activated mitochondrial apoptosis by inhibiting protective mitophagy. Re-activation of mitophagy abolished the pro-apoptotic effects of matrine on HepG2 cells. Molecular investigations further confirmed that matrine regulated mitophagy via the PINK1/Parkin pathways. Matrine blocked the PINK1/Parkin pathways and repressed mitophagy, whereas activation of the PINK1/Parkin pathways increased mitophagy activity and promoted HepG2 cell survival in the presence of matrine. Together, our data indicated that matrine promoted HepG2 cell apoptosis through a novel mechanism that acted via inhibiting mitophagy and the PINK1/Parkin pathways. This finding provides new insight into the molecular mechanism of matrine for treating liver cancer and offers a potential target to repress liver cancer progression by modulating mitophagy and the PINK1/Parkin pathways.


Two-year impact of personality-targeted, teacher-delivered interventions on youth internalizing and externalizing problems: a cluster-randomized trial.
To assess the 2-year impact of teacher-delivered, brief, personality-targeted interventions on internalizing and externalizing symptoms in an adolescent U.K. sample. This cluster-randomized trial was run in 19 London schools (N = 1,024 adolescents). Trained school-based professionals delivered two 90-minute, CBT-based group interventions targeting 1 of 4 personality-risk profiles: anxiety sensitivity, hopelessness, impulsivity, or sensation seeking. Self-report depression, anxiety, and conduct disorder symptoms were assessed at 6-month intervals. Interventions were associated with significantly reduced depressive, anxiety, and conduct symptoms (p < .05) over 2 years in the full sample, reduced odds of severe depressive symptoms (odds ratio [OR] = 0.74, CI = 0.58-0.96), and conduct problems (OR = 0.79, CI = 0.65-0.96), and a nonsignificant reduction in severe anxiety symptoms (OR = 0.79, CI = 0.59-1.05). Evaluating a priori personality-specific hypotheses revealed strong evidence for impulsivity-specific effects on severe conduct problems, modest evidence of anxiety sensitivity-specific effects on severe anxiety, and no evidence for hopelessness-specific effects on severe depressive symptoms. Brief, personality-targeted interventions delivered by educational professionals can have a clinically significant impact on mental health outcomes in high-risk youth over 2 years, as well as personality-specific intervention effects in youth most at risk for a particular problem, particularly for youth with high levels of impulsivity. Clinical trial registration information-Adventure: The Efficacy of Personality-Targeted Interventions for Substance Misuse and Other Risky Behaviors as Delivered by Educational Professionals.


Severe tumor lysis syndrome following splenic irradiation.
A 72-year-old man suffering from non-Hodgkin's lymphoma is described. After failing to respond to chlorambucil-prednisone regimen for three months, he was treated by splenic irradiation (total dose 500 cGY) in 10 consecutive daily doses. Two days after the last irradiation, the patient developed acute tumor lysis syndrome (TLS) with extreme blood levels of uric acid (33.7 mg/dl), phosphorus (13.7 mg/dl), potassium (6.08 mEq/l), and calcium (6.8 mg/dl). It should be remembered that the acute TLS, which usually occurs following chemotherapy, can also be radiation-induced.


Human DNA helicase B interacts with the replication initiation protein Cdc45 and facilitates Cdc45 binding onto chromatin.
The chromosomal DNA replication in eukaryotic cells begins at replication initation sites, which are marked by the assembly of the pre-replication complexes in early G1. At the G1/S transition, recruitment of additional replication initiation proteins enables origin DNA unwinding and loading of DNA polymerases. We found that depletion of the human DNA helicase B (HDHB) inhibits the initiation of DNA replication, suggesting a role of HDHB in the beginning of the DNA synthesis. To gain insight into the function of HDHB during replication initiation, we examined the physical interactions of purified recombinant HDHB with key initiation proteins. HDHB interacts directly with two initiation factors TopBP1 and Cdc45. In addition we found that both, the N-terminus and helicase domain of HDHB bind to the N-terminus of Cdc45. Furthermore depletion of HDHB from human cells diminishes Cdc45 association with chromatin, suggesting that HDHB may facilitate Cdc45 recruitment at G1/S in human cells.


Uric acid and urea in relation to protein catabolism in long-term fasting geese.
Five ganders were subjected to an experimental fast comparable to that which spontaneously occurs during breeding in domestic geese, and during migration and breeding in various wild birds. Plasma uric acid and urea concentrations, and their excretion as a proportion of total nitrogen excretion, were studied in relation to daily change in body mass per unit body mass, mg/mdt. This variable has previously been found to reflect changes in protein catabolism over the three phases of fast: I, dm/mdt and protein utilization both decrease; II, they are maintained at a low value; and III, they increase. In the fed state, daily total nitrogen excretion was 5 gN X 24 h-1; uric acid, ammonia and urea accounted for 51, 15 and 5% respectively. The high remaining proportion of excreted nitrogen (29%), after subtraction of uric acid-N, ammonia-N and urea-N to total nitrogen, accords with the literature. During fasting, the changes in daily excretion of uric acid, urea, ammonia and total nitrogen followed a pattern essentially similar to that for dm/mdt. Uric acid accounted for a progressively increasing fraction of total nitrogen, up to 76% at the end of phase III, while urea remained at a constant 5%. Plasma concentrations of both uric acid and urea followed similar trends during the fast, in particular both increasing during phase III, i.e. when there was a rise in nitrogen excretion. This suggests they could be used as an index in field investigations, to determine whether birds which naturally fast in connection with specific activities have entered into the situation where proteins are no longer spared.


Antireflux ureteral stent proof of concept assessment after minimally invasive treatment of obstructive uropathy in animal model.
To assess the efficacy of a new anti-reflux intraureteral stent design in a swine model after minimally invasive treatment of ureteral stricture to reduce ureteral stent morbidity, previous to manufacture this design in a biodegradable fashion. Twenty-eight female pigs were included. The study began with a cystoscopic, nephrosonographic and contrast fluoroscopic assessment. Afterwards, obstructive uropathy model in right ureter was created. Obstruction was confirmed 6 weeks later and animals were randomly distributed into 2 groups. Group I underwent laser endopyelotomy and Group-II laparoscopic pyeloplasty A 3Fr anti-reflux intraureteral stent was placed 6 weeks. Follow-up evaluations were performed at 3-6 weeks. The final follow-up was completed at 5 months and included the aforementioned diagnostic methods and pathological study. None of the study animals showed any vesicoureteral reflux signs or ureteral orifice injury. There were no urinomas or ureteric fistulas. The dislodgement rate was 10.7%. After 6 weeks of stenting, 71.4% of ureters showed ureteral peristalsis below the stent, and 100% at the final follow-up. After pathological assessment, no differences were shown at UPJ and healing in the incised area was correct in both groups. The new stent design avoids vesicoureteral reflux and bladder trigone irritation, consequently might reduce morbidity associated with double pigtail ureteral stents. This study also shows that it is only necessary temporary scaffolding the incised ureteral segment and not the entire length of the ureter after minimally invasive surgery. It is also necessary to manufacture this design in a biodegradable material, thus avoiding its removal.


Cardiac arrest secondary to subclavian artery injury in blunt chest trauma: A lifesaving emergency surgery in COVID crises.
A 25-year-old male vehicle driver had a road traffic accident and sustained a blunt chest injury. His chest x-ray in the emergency department showed left hemithorax opacification. A chest drain Fr32 was inserted, and 1300ml of Blood drained out. While having a computed tomographic scan of the thorax scan, he had a cardiac arrest and after Cardiopulmonary Resuscitation (CPR) he was transferred to our tertiary care hospital on a mechanical ventilator and massive ionotropic support (adrenaline and noradrenaline) with a blood pressure of 50/24 mmHg. We performed a lifesaving emergency thoracotomy in a supine position with all COVID precautions, as COVID status was not available before hospitalization. After the repair of the Subclavian artery patient recovered completely and was discharged for follow-up in outpatient.


A novel lncRNA SNHG29 regulates EP300- related histone acetylation modification and inhibits FLT3-ITD AML development.
Internal tandem duplication (ITD) mutations within the FMS-like tyrosine kinase-3 (FLT3) occur in up to 25% of acute myeloid leukemia (AML) patients and indicate a very poor prognosis. The role of long noncoding RNAs (lncRNAs) in FLT3-ITD AML progression remains unexplored. We identified a novel lncRNA, SNHG29, whose expression is specifically regulated by the FLT3-STAT5 signaling pathway and is abnormally down-regulated in FLT3-ITD AML cell lines. SNHG29 functions as a tumor suppressor, significantly inhibiting FLT3-ITD AML cell proliferation and decreasing sensitivity to cytarabine in vitro and in vivo models. Mechanistically, we demonstrated that SNHG29's molecular mechanism is EP300-binding dependent and identified the EP300-interacting region of SNHG29. SNHG29 modulates genome-wide EP300 genomic binding, affecting EP300-mediated histone modification and consequently influencing the expression of varies downstream AML-associated genes. Our study uncovers a novel molecular mechanism for SNHG29 in mediating FLT3-ITD AML biological behaviors through epigenetic modification, suggesting that SNHG29 could be a potential therapeutic target for FLT3-ITD AML.


Proton-Reservoir Hydrogel Electrolyte for Long-Term Cycling Zn/PANI Batteries in Wide Temperature Range.
Advanced aqueous batteries are promising for next generation flexible devices owing to the high safety, yet still requiring better cycling stability and high capacities in wide temperature range. Herein, a polymeric acid hydrogel electrolyte (PAGE) with 3 M Zn(ClO4 )2 was fabricated for high performance Zn/polyaniline (PANI) batteries. With PAGE, even at -35 °C the Zn/Zn symmetrical battery can keep stable for more than 1 500 h under 2 mA cm-2 , and the Zn/PANI battery can provide ultra-high stable specific capacity of 79.6 mAh g-1 for more than 70 000 cycles at 15 A g-1 . This can be mainly ascribed to the -SO3 - H+ function group in PAGE. It can generate constant protons and guide the (002) plane formation to accelerate the PANI redox reaction kinetics, increase the specific capacity, and suppress the side reaction and dendrites. This proton-supplying strategy by polymeric acid hydrogel may further propel the development of high performance aqueous batteries.


Interaction of proteins with immobilized Cu2+. Quantitation of adsorption capacity, adsorption isotherms and equilibrium constants by frontal analysis.
The interaction of lysozyme, ovalbumin, bovine and pig serum albumins with Cu2+ immobilized on Chelating Sepharose Fast Flow or TSK gel chelate-5PW was studied by frontal analysis at various initial concentrations of these solutes. The chromatographic data so obtained served as a basis for evaluating some relevant affinity chromatography parameters by adapting previously reported equations to this system. The TSK-based adsorbent had lower adsorption capacity for all the model proteins compared to the agarose-based adsorbent, due primarily to its lower porosity which has a marked influence on the accessibility of the immobilized ligand to the proteins. On the other hand, the TSK-based adsorbent offers almost ideal conditions for studying adsorption equilibria under column chromatographic conditions. The adsorption capacity of these adsorbents for the model proteins ranges from about 0.6 to 7 mumol/ml, equivalent to 40-100 mg/ml, of adsorbent. The following equilibrium constants for the interaction of the proteins with immobilized Cu2+ were obtained: lysozyme, 1.8.10(4); ovalbumin, 1.5.0(5); BSA, 1.7.10(5); PSA, 3.7.10(5) and imidazole, 8.10(3) M-1. Despite the comparatively low affinity of imidazole for the adsorbent, it is an effective competing ligand, at comparatively high concentrations, for adsorbed proteins primarily because all adsorption sites are available to it. The results obtained suggest that about 1/3 to 1/2 of the potential adsorption sites on the model proteins are involved in forming coordination complexes with Cu2+ immobilized to covalently bound iminodiacetate groups on insoluble gel matrices.


The range of antiferromagnetic coupling governs the conductivity: semiconducting behavior and ammonia gas sensing property of diamagnetic hexaradical-containing tetranuclear CoIII4 cluster and its nonradical congener.
Long-range antiferromagnetic coupling impeded electron flow through the hexaradical-containing tetranuclear CoIII4 complex (1), while the nonradical-containing tetranuclear CoIII4 complex (2), with no paramagnetic centres, was a semiconductor and sensed NH3 efficiently at room temperature (25 °C).


Breast-feeding of allergic infants.
Infants may have allergic disease even during exclusive breast-feeding. The aim of this study was to evaluate whether allergic infants should continue breast-feeding. We studied 100 infants who had atopic eczema during exclusive breast-feeding. The extent and severity of the eczema, allergic sensitization, and the patients' growth and nutrition were assessed during and after cessation of breast-feeding. The mean body length SD score decreased at the onset of allergic disease, and an association was seen between the duration of symptoms and poor growth (r = -.23, P =.04). Some improvement could be achieved by strict elimination diet by the mothers. The atopic eczema improved significantly after breast-feeding was stopped: SCORAD score 20 (range 15 to 27) during and 7 (range 4 to 11) after breast-feeding; t = 5.38, P <.0001, and the relative length of patients increased, in parallel with improved nutritional parameters. Breast-feeding should be promoted for primary prevention of allergy, but breast-fed infants with allergy should be treated by allergen avoidance, and in some cases breast-feeding should also be stopped. This particularly applies to infants with atopic eczema who also have impaired growth.


Temperature-field phase diagram of extreme magnetoresistance.
The recent discovery of extreme magnetoresistance (XMR) in LaSb introduced lanthanum monopnictides as a new platform to study this effect in the absence of broken inversion symmetry or protected linear band crossing. In this work, we report XMR in LaBi. Through a comparative study of magnetotransport effects in LaBi and LaSb, we construct a temperature-field phase diagram with triangular shape that illustrates how a magnetic field tunes the electronic behavior in these materials. We show that the triangular phase diagram can be generalized to other topological semimetals with different crystal structures and different chemical compositions. By comparing our experimental results to band structure calculations, we suggest that XMR in LaBi and LaSb originates from a combination of compensated electron-hole pockets and a particular orbital texture on the electron pocket. Such orbital texture is likely to be a generic feature of various topological semimetals, giving rise to their small residual resistivity at zero field and subject to strong scattering induced by a magnetic field.


Abatacept in the long-term treatment of rheumatoid arthritis.
The last decade has been an era of exciting and innovative therapeutic targets in the treatment of moderate-to-severe rheumatoid arthritis. One such treatment that acts by disrupting T-cell activation is abatacept, which is currently used in patients who have had an inadequate clinical response to traditional disease-modifying drugs or anti-TNF therapies. As newer therapies emerge, issues that need addressing include: long-term drug tolerance, adverse events, sustained clinical response, prevention of progression in structural damage and retention rates. In this article we discuss a recently published paper by Kremer et al. that reported 3-year data on safety, efficacy and radiographic progression in patients enrolled in a clinical trial of abatacept, as well as the advantages and limitations of long-term extension studies.


Characterization of a murine model of endothelial dysfunction induced by chronic intraperitoneal administration of angiotensin II.
Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1β, IL17A, IL4, TGFβ, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.


Retracted: Data Sharing Method of College Dance Teaching Resource Database Based on PSO Algorithm.
[This retracts the article DOI: 10.1155/2022/2162981.].


Implantable cardioverter-defibrillator therapy: influence of left ventricular function on long-term results.
The degree of left ventricular impairment in an acknowledged important prognostic marker of long-term outcome for patients being evaluated for implantation of cardioverter-defibrillators. Just how left ventricular function impacts freedom from all-cause mortality, as well as from sudden death and cardiac death, is a subject of current major debate, and is analyzed hereunder from a large, recent multicenter ICD patient cohort. The multicenter database consists of data from 361 patients receiving implantable cardioverter-defibrillators for standard indications, that is, documented episodes of ventricular fibrillation or sustained ventricular tachycardias with poor hemodynamic toleration. Data were collected from 1988 to 1995 at three centers in Germany. Two-hundred and three patients (56%) had a left ventricular ejection fraction (LVEF) > 0.30 (group I), and 158 patients (44%) had a LVEF < or = 0.30 respectively (group II). The mean follow-up was 23.9 months (range 3-98 months). Overall survival at 5 years for group II patients was lower, as expected, at 74.1% versus 94.2%, respectively (P < 0.0001). Mortality was higher for each different cause of death in group II patients than in Group I: sudden arrhythmic deaths, 5 versus 1 (P < 0.048); nonsudden cardiac deaths, 16 versus 5 (P < 0.002); noncardiac deaths, 7 versus 2 (P < 0.03). Group II patients received a higher rate of at least one presumably appropriate shock at 86 (54.4%) versus 89 (43.8%) in group I (P < 0.05). However (and somewhat surprisingly), neither the time from ICD implantation to death, comparing only the patients who died, nor the event-free probability of appropriate shocks due to very rapid, sustained ventricular arrhythmias (> 230 beats/min), including a presumed risk of sudden arrhythmogenic death, differed between groups I and II. Sudden cardiac death was only marginally affected by LVEF (group I, 1.5% actuarial, 5-year survival 99.5%; group II, 3.1% and 95.8%, respectively). Therefore, the lower overall survival in ICD patients with LVEF < or = 0.30 resulted mainly from causes of death that cannot be directly influenced by cardioverter-defibrillator therapy. However, because group II patients had a far higher incidence of at least one ventricular tachyarrhythmia terminated by ICD shocks than group I patients, they also probably derived benefit from ICD therapy.


The effects of maternal dietary treatments with natural PPAR ligands on lipid metabolism in fetuses from control and diabetic rats.
Maternal diabetes impairs fetal development and growth. We studied the effects of maternal diets enriched in unsaturated fatty acids capable of activating peroxisome proliferator-activated receptors (PPARs) on the concentrations of 15deoxyDelta12,14PGJ2 (15dPGJ2), lipid mass, and the de novo lipid synthesis in 13.5-day fetuses from control and diabetic rats. Diabetes was induced by neonatal streptozotocin administration (90 mg/kg). Rats were treated with a standard diet supplemented or not with 6% olive oil or 6% safflower oil from days 0.5 to 13.5 of gestation. Fetuses from diabetic rats fed with the standard diet showed reduced 15dPGJ2 concentrations, whereas maternal treatments with olive and safflower oils increased 15dPGJ2 concentrations. Fetuses from diabetic rats showed increased concentrations of phospholipids and increased synthesis of triglycerides, phospholipids, cholesterol and free fatty acids. Diabetic rat treatments with olive and safflower oils reduced phospholipids, cholesterol, and free fatty acid concentrations and the de novo lipid synthesis in the fetuses. These effects were different from those observed in fetuses from control rats, and seem not to involve PPARgamma activation. In conclusion, olive oil- and safflower oil-supplemented diets provide beneficial effects in maternal diabetes, as they prevent fetal impairments in 15dPGJ2 concentrations, lipid synthesis and lipid accumulation.


Importance of local proliferation in the expanding Kupffer cell population of rat liver after zymosan stimulation and partial hepatectomy.
Partial hepatectomy and a single intravenous injection of zymosan were used to provoke expansion of the Kupffer cell population in rat liver. The number of Kupffer cells per microscopic field increased exponentially for 4 to 5 days after either stimulation. During this exponential growth phase, high mitotic activity of Kupffer cells was observed. The rate of mitosis, based on counts of cells arrested in metaphase by vinblastin, was compared with the increase in total cell population. During the first 3 days after partial hepatectomy, local proliferation was sufficient to explain the increase in population since the mean potential doubling time was 1.3 days compared to an observed doubling time of 3.7 days. During the first 3 days after zymosan stimulation, observed doubling time was 4.3 days compared with the mean potential doubling time of 5.2 days which led to the conclusion that growth is largely due to local proliferation of Kupffer cells. In both experimental situations, extrahepatic recruitment of "resident-type" macrophages was required during the last 2 days of the growth phase, since mitotic activity became too low to explain the observed growth. Proliferating Kupffer cells had characteristics of mature resident macrophages and were, therefore, considered to be different from elicited "exudate-type" cells, such as monocytes.


NMR backbone assignments of the tyrosine kinase domain of human fibroblast growth factor receptor 1.
Members of the fibroblast growth factor receptor tyrosine kinase family (FGFR1-4) play an important role in many signalling cascades. Although tightly regulated, aberrant activity of these enzymes may lead to, or become features of, disease pathologies including cancer. FGFR isoforms have been the subject of drug discovery programmes, with a number of kinase-domain inhibitors in pre-clinical and clinical development. Here, we present the first (83% complete) backbone resonance assignments of apo-FGFR1 kinase.


Artemisinin-derived artemisitene blocks ROS-mediated NLRP3 inflammasome and alleviates ulcerative colitis.
Artemisinins are well-known antimalarial drugs with clinical safety. In addition to antimalarial effects, their anti-inflammatory and immunoregulatory properties have recently attracted much attention in the treatment of inflammatory diseases. However, these artemisinins only have sub-millimolar anti-inflammatory activity in vitro, which may pose a high risk of toxicity in vivo with high doses of artemisinins. Here, we identified another derivative, artemisitene, which can increase the activity of inhibiting the NLRP3 pathway by more than 200-fold through introducing a covalent binding group while retaining the peroxide bridge structure. Mechanistically, artemisitene inhibits the production of ROS (especially mtROS) and prevents the assembly and activation of NLRP3 inflammasome, thereby inhibiting IL-1β production. In addition, it can also block IL-1β secretion mediated by NLRC4 and AIM2 inflammasome and IL-6 production. Furthermore, treatment with artemisitene significantly attenuated inflammatory response in DSS-induced ulcerative colitis. Our work provides a potential artemisinin derivative, which is worthy of further structural optimization based on pharmacokinetic properties as a drug candidate for inflammatory disorders.


Continuous glucose monitoring in older people with diabetes and memory problems: a mixed-methods feasibility study in the UK.
Older people with diabetes are at increased risk of harm from hypoglycaemia, particularly where there are coexisting memory problems. Continuous glucose monitoring (CGM) offers important benefits in terms of detecting hypoglycaemia, but the feasibility of use and extent of data capture has not been tested in this patient group. Our objective was to investigate the feasibility of trialling a CGM intervention in the community setting in older people with diabetes and memory problems. Mixed-methods feasibility study. Community dwellings in the UK. Patients aged ≥65 with diabetes and abbreviated mental test score ≤8 or known dementia. FreeStyle Libre CGM. Feasibility criteria were numbers of eligible patients, recruitment, attrition, extent of capture of glucose readings and adverse events. Qualitative interview. We identified 49 eligible participants; 17 consented, but 5 withdrew before recording of data because they or their carers felt unable to manage study procedures. 12 participants (mean age 85 years) completed the study without adverse events. Data capture across 14 days ranged between 3% and 92% (mean 55%); 6 participants had <60% capture. Hypoglycaemic events were recorded in six out of nine insulin users. Qualitative interviews found: the device does not interfere with daily activities, usability and comfort was positive, and it was helpful for carers in monitoring participants' glucose concentrations. The device was acceptable to participants, and carers reported greater ease in monitoring the participant's glucose concentrations. However, completeness of data capture varied considerably with this device due to the need for users to conduct ≥3 scans per day. Real-time devices with automated data transfer may be more suitable in older people with memory problems.


[Effect of an imidazobenzodiazepine (RO 15-1788) on aggressive behavior in mice].
Imidazobenzodiazepine (Ro 15-1788, 5 mg/kg) similarly to a lose dose of apomorphine (0.1 mg/kg) decreased the intensity of footshock aggression in male rats. Ro 15-1788 significantly potentiated the antiaggressive action of apomorphine. Pirenperone (0.01 mg/kg) potentiated the effect of both drugs, whereas haloperidol (0.01 mg/kg) had an opposite action. After long-term treatment with apomorphine and Ro 15-1788 the tolerance to their antiaggressive action developed. This change was in agreement with increased serotonin metabolism in the forebrain. Unlike the action on aggressive behavior, Ro 15-1788 similarly to haloperidol (0.05 mg/kg) decreased the motor depressant effect of apomorphine (0.01 mg/kg) in mice. This effect correlated with the lowered serotonin metabolism after Ro 15-1788 administration. Unlike apomorphine, Ro 15-1788 reversed catalepsy induced by haloperidol (0.25 mg/kg). Administration of pirenperone (0.03 mg/kg) and destruction of serotoninergic terminals by p-chloroamphetamine (2 X 15 mg/kg) significantly potentiated the sedative action of apomorphine. It appears that different action of Ro 15-1788 on behavioral effects of apomorphine is related to different influence of Ro-1788 on serotoninergic processes in the striatum and limbic structures.


Hyperpyrexia of uncertain origin.
Hyperpyrexia occurring in a 27-year-old woman undergoing eye surgery is described. The cause, although open to doubt, appeared to be a thyroid storm.


A randomised controlled trial to evaluate a medication monitoring system for TB treatment.
BACKGROUND: Adherence to TB treatment and therefore treatment success could be improved using digital adherence technology.OBJECTIVE: To evaluate the effectiveness of a medication event reminder monitor system (MERM) on treatment success and treatment adherence in patients with drug-susceptible pulmonary TB in Perú.METHODS: This was an experimental, randomised, open-label, controlled study conducted among patients in the second phase of TB treatment. The intervention group received their medications through MERM with the support of a treatment monitor, whereas the control group used the usual strategy. Participants were followed until they completed the 54 doses of the second phase of treatment.RESULTS: The study included 53 patients in each group; four in the intervention group withdrew from the study. Treatment success was significantly more frequent in the MERM group (RR 1.15, 95% CI 1.02-1.30; P = 0.0322). There was no significant difference in the adherence outcomes; however, the percentage of patients who missed at least one dose and patients with more than 10% of total doses missed were lower in the intervention group.CONCLUSION: The use of MERM in the second phase of treatment showed a significant improvement in the treatment success rate in patients with drug-susceptible pulmonary TB.


Virtual reality in the rehabilitation process for individuals with cerebral palsy and Down syndrome: A systematic review.
Childhood neurological diseases result in neuromotor impairment, which affects selective motor control, compromising the acquisition of motor skills and functional independence. The positive results achieved with virtual reality are believed to be related to training in an interactive environment that provides a broad range of activities and scenarios with multiple sensory channels, enabling the creation of exercises at an intensity based on individual need. Therefore, a review was conducted to answer the following question: What are the possible effects of virtual reality for the pediatric population, specifically children with cerebral palsy and Down syndrome? The objective of the present study was to conduct a systematic review of the literature to determine the possible effects of virtual reality therapy in children with cerebral palsy and Down's syndrome. The PubMed, Bireme, Scielo and PEDro electronic databases were searched in the period from January to March 2016 using the following keywords: Down syndrome and virtual reality, virtual reality and cerebral palsy, virtual reality and neuropediatrics, and Down's syndrome and virtual reality. Only randomized controlled trials published in English in the previous 10 years (2007-2016) that addressed the specific purpose of this review and achieved a score of at least 4 points on the PEDro methodological quality scale were eligible for inclusion. The initial research led to the retrieval of 214 articles, which were analyzed considering the inclusion criteria. Eighteen articles were submitted to an appraisal of methodological quality using the PEDro scale, only five of which received a score of four or more points and were described in the present review. Three of the studies selected analyzed children with cerebral palsy and two analyzed children with Down syndrome. Despite the different physiopathological characteristics of the two conditions, the authors employed similar therapeutic methods and evaluations. The results of the studies demonstrated that virtual reality training either alone or combined with motor training leads to improvements in sensory-motor functions and can be used as a complement to other successful rehabilitation interventions in the two populations. Based on the results of the studies included in the present systematic review, despite differences in the characteristics of each population, the objectives and methods proposed by the authors were similar and virtual reality demonstrated promising effects for individuals with cerebral palsy and Down syndrome.


The Tudor domain of the PHD finger protein 1 is a dual reader of lysine trimethylation at lysine 36 of histone H3 and lysine 27 of histone variant H3t.
PHF1 associates with the Polycomb repressive complex 2 and it was demonstrated to stimulate its H3K27-trimethylation activity. We studied the interaction of the PHF1 Tudor domain with modified histone peptides and found that it recognizes H3K36me3 and H3tK27me3 (on the histone variant H3t) and that it uses the same trimethyllysine binding pocket for the interaction with both peptides. Since both peptide sequences are very different, this result indicates that reading domains can have dual specificities. Sub-nuclear localization studies of full-length PHF1 in human HEK293 cells revealed that it co-localizes with K27me3, but not with K36me3, and that this co-localization depends on the trimethyllysine binding pocket indicating that K27me3 is an in vivo target for the PHF1 Tudor domain. Our data suggest that PHF1 binds to H3tK27me3 in human chromatin, and H3t has a more general role in Polycomb regulation.


Surfactant-assisted UV-photolysis of nitroarenes.
Photochemical transformations (lambda-254 nm) of 2,4-dinitrotoluene (2,4-DNT) in aqueous solutions containing the cationic surfactant cetyltrimethylammonium (CTA) and the anionic nucleophile borohydride (BH4-) were investigated. The overall decay rate was enhanced at CTA concentrations above the critical micelle concentration (cmc) when stoichiometric excess BH4- was present in solution. A kinetic model that separates the overall reaction rate into micellar and aqueous pseudo-phase components indicates transformation in micelles is 17 times faster that in the homogeneous water phase under those conditions investigated. Intermediate products were identified by comparing the HPLC retention times and ultraviolet-visible absorption spectra of product peaks to those of analytical standards. 2-Methyl-5-nitroaniline, 4-nitrotoluene, 2-nitrotoluene, 4-methyl-3-nitroaniline, 2,4-diaminotoluene, o-toluidine, 1,3-dinitrobenzene, 3-nitroaniline, p-cresol, and 2,4-diaminophenol were identified as photo-transformation intermediates or products.


Serotype identification of Australian bluetongue viruses using a rapid fluorescence inhibition test.
Rapid serotyping of bluetongue virus (BTV) isolates is required to facilitate the choice of an appropriate serotype-specific vaccine in a disease situation or to improve surveillance of BTV serotype prevalence. This communication describes the development and validation of a bluetongue virus fluorescent inhibition test (BTV FIT) as a rapid method to serotype Australian BTV isolates. The BTV FIT uses virus neutralisation principles similar to those used in the rabies rapid fluorescent focus inhibition test. The BTV FIT has the ability to provide an accurate serotype identification within 24 h thereby abbreviating the serotyping process by 3-4 days relative to conventional virus neutralisation assays and making the BTV FIT comparable time-wise with the polymerase chain reaction technique. The development of the BTV FIT is described using BTV reference viruses which have been isolated in Australia, and validation of the assay by assessment of five Australian BTV isolates of unknown serotype by comparison with the plaque inhibition method. The use of the BTV FIT readily facilitated rapid and accurate serotype identification of Australian BTV reference viruses and five unknown BTV isolates with results indicating full agreement with the plaque inhibition method.


Competition between herbivourous fishes and urchins on Caribbean reefs.
When the common sea urchin Diadema antillarum was removed from a 50 m strip of reef in St. Thomas, US Virgin Islands, cover of upright algae and the grazing rates and densities of herbivorous parrotfish and surgeonfish increased significantly within 11-16 weeks when compared to immediately adjacent control areas. Sixteen months after removal, Diadema had recovered to 70% of original density, abundance of upright algae no longer differed between removal and control areas, and the abundance and grazing activity of herbivorous fish in the removal was approaching equivalence with control areas. On a patch reef in St. Croix that had been cleared of Diadema 10-11 years earlier (Ogden et al. 1973b), urchins had recovered to only 50-60% of original density. This reef still showed significantly higher rates of grazing by fish and a significantly greater density of parrotfish and surgeonfish than a nearby control reef where Diadema densities had not been altered. These results indicate that high Diadema densities (7-12/m2 for this study) may suppress the densities of herbivorous fish on Caribbean reefs.


Can a modified anterior external fixator provide posterior compression of AP compression type III pelvic injuries?
Current anterior fixators can close a disrupted anterior pelvic ring. However, these anterior constructs cannot create posterior compressive forces across the sacroiliac joint. We explored whether a modified fixator could create such forces. We determined whether (1) an anterior external fixator with a second anterior articulation (X-frame) would provide posterior pelvic compression and (2) full pin insertion would deliver higher posterior compressive forces than half pin insertion. We simulated AP compression Type III instability with plastic pelvis models and tested the following conditions: (1) single-pin supraacetabular external fixator (SAEF) using half pin insertion (60 mm); (2) SAEF using full pin insertion (120 mm); (3) modified fixator with X-frame using half pin insertion; (4) modified fixator using full pin insertion; and (5) C-clamp. Standardized fracture compression in the anterior and posterior compartment was performed as in previous studies by Gardner. A force-sensitive sensor was placed in the symphysis and posterior pelvic ring before fracture reduction and the fractures were reduced. The symphyseal and sacroiliac compression loads of each application were measured. The SAEF exerted mean compressions of 13 N and 14 N to the posterior pelvic ring using half and full pin insertions, respectively. The modified fixator had mean posterior compressions of 174 N and 222 N with half and full pin insertions, respectively. C-clamp application exerted a mean posterior load of 407 N. Posterior compression on the pelvis was improved using an X-frame as an anterior fixation device in a synthetic pelvic fracture model. This additive device may improve the initial anterior and posterior stability in the acute management of unstable and life-threatening pelvic ring injuries.