Lifetime incidence risk for gastric cancer in the Helicobacter pylori-infected and uninfected population in Japan: A Monte Carlo simulation study.
Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long-term cumulative risks between H. pylori-infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori-infected and uninfected populations by using population-based cancer registry data and birth year-specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population-based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori-infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan.


The controlled generation of functional basal forebrain cholinergic neurons from human embryonic stem cells.
An early substantial loss of basal forebrain cholinergic neurons (BFCN) is a constant feature of Alzheimer's disease and is associated with deficits in spatial learning and memory. The ability to selectively control the differentiation of human embryonic stem cells (hESCs) into BFCN would be a significant step toward a cell replacement therapy. We demonstrate here a method for the derivation of a predominantly pure population of BFCN from hESC cells using diffusible ligands present in the forebrain at developmentally relevant time periods. Overexpression of two relevant human transcription factors in hESC-derived neural progenitors also generates BFCN. These neurons express only those markers characteristic of BFCN, generate action potentials, and form functional cholinergic synapses in murine hippocampal slice cultures. siRNA-mediated knockdown of the transcription factors blocks BFCN generation by the diffusible ligands, clearly demonstrating the factors both necessary and sufficient for the controlled derivation of this neuronal population. The ability to selectively control the differentiation of hESCs into BFCN is a significant step both for understanding mechanisms regulating BFCN lineage commitment and for the development of both cell transplant-mediated therapeutic interventions for Alzheimer's disease and high-throughput screening for agents that promote BFCN survival.


A Bone Health Intervention for Chinese Immigrants in Santa Clara County.
Among Chinese immigrants, osteoporosis is undertreated, misdiagnosed, and a leading cause of fragility fractures. In orthopaedic surgery departments, prevention education and health behavior change programs are necessary to improve their bone health. The purpose of this study was to examine the effectiveness of an osteoporosis prevention education program on participants' self-efficacy with regard to exercise and nutrition when provided by an orthopaedic surgery team during an annual Chinese Health Fair in Santa Clara County, CA. This pilot study used a single-group pretest and posttest design. Chinese immigrants at risk of osteoporosis were recruited during a 1-day health fair. The Bone Health Intervention (BHI) included orthopaedic surgeon consultation, visual aids including osteoporosis images and bone models, a video that included a discussion on calcium and vitamin D in the Chinese diet and culturally-acceptable exercise, and osteoporosis educational handouts. The Osteoporosis Self-Efficacy Scale (OSES) was utilized to measure participants' confidence in the ability to participate in self-care behaviors related to physical activity and calcium intake before and after the intervention. Paired t tests were used to compare participants' OSES scores pre- and postintervention. There was a significant increase in mean OSES scores postintervention, indicating that the intervention could be an effective method of increasing participants' self-efficacy regarding calcium intake and time spent in exercising. These results indicate that a culturally meaningful education program can potentially reduce fragility fracture risk. Orthopaedic health providers are ideal candidates to deliver preventive care education to improve outcomes for Chinese immigrants.


Reperfusion injury pathophysiology in sickle transgenic mice.
Reperfusion of tissues after interruption of their vascular supply causes free-radical generation that leads to tissue damage, a scenario referred to as "reperfusion injury." Because sickle disease involves repeated transient ischemic episodes, we sought evidence for excessive free-radical generation in sickle transgenic mice. Compared with normal mice, sickle mice at ambient air had a higher ethane excretion (marker of lipid peroxidation) and greater conversion of salicylic acid to 2,3-dihydroxybenzoic acid (marker of hydroxyl radical generation). During hypoxia (11% O(2)), only sickle mice converted tissue xanthine dehydrogenase to oxidase. Only the sickle mice exhibited a further increase in ethane excretion during restitution of normal oxygen tension after 2 hours of hypoxia. Only the sickle mice showed abnormal activation of nuclear factor-kappaB after exposure to hypoxia-reoxygenation. Allopurinol, a potential therapeutic agent, decreased ethane excretion in the sickle mice. Thus, sickle transgenic mice exhibit biochemical footprints consistent with excessive free-radical generation even at ambient air and following a transient induction of enhanced sickling. We suggest that reperfusion injury physiology may contribute to the evolution of the chronic organ damage characteristic of sickle cell disease. If so, novel therapeutic approaches might be of value.


Differential expression patterns of the tight junction-associated proteins occludin and claudins in secretory and mature ameloblasts in mouse incisor.
Tight junctions (TJs) function primarily as a barrier against paracellular transport between epithelial cells and are composed mainly of occludin (OLD) and claudins (CLDs). The CLD family consists of 24 members that show tissue- or cell-specific expression. Ameloblasts, which originate from the oral epithelium, form enamel, and enamel proteins and minerals are transported across the ameloblastic layer during amelogenesis. We immunohistochemically examined the distribution patterns of TJs in ameloblasts by observing the expression patterns of OLD and CLDs (CLD-1 to CLD-10). Secretory ameloblasts contained OLD and CLD-1, -8, and -9 at the distal end of the cell. In mature ameloblasts, OLD and CLD-1, -6, -7, -8, -9, and -10 were present mainly at both the distal and proximal ends of the cell, regardless of whether the ameloblasts were ruffle-ended or smooth-ended. Mature ameloblasts in which only the proximal ends were stained for OLD and CLDs were also found. These results indicate that the expression patterns of CLDs and the distribution patterns of TJs change drastically between the secretory and mature ameloblast stages, suggesting that these patterns reflect the different functions of these cells, specifically in the transport of proteins and ions for enamel formation.


The Pathway Tools cellular overview diagram and Omics Viewer.
The Pathway Tools cellular overview diagram is a visual representation of the biochemical network of an organism. The overview is automatically created from a Pathway/Genome Database describing that organism. The cellular overview includes metabolic, transport and signaling pathways, and other membrane and periplasmic proteins. Pathway Tools supports interrogation and exploration of cellular biochemical networks through the overview diagram. Furthermore, a software component called the Omics Viewer provides visual analysis of whole-organism datasets using the overview diagram as an organizing framework. For example, gene expression and metabolomics measurements, alone or in combination, can be painted onto the overview, as can computed whole-organism datasets, such as predicted reaction-flux values. The cellular overview and Omics Viewer provide a mechanism whereby biologists can apply the pattern-recognition capabilities of the human visual system to analyze large-scale datasets in a biologically meaningful context. SRI's BioCyc.org website provides overview diagrams for more than 200 organisms. This article describes enhancements to the overview made since a 1999 publication, including the automatic layout capability, expansion of the cellular machinery that it includes, new semantic zooming and poster-generating capabilities, and extension of the Omics Viewer to support painting of metabolites, animations and zooming to individual pathway diagrams.


Cognitive reserve in multiple sclerosis.
Cognitive impairment is common among persons with multiple sclerosis (MS), but some patients are able to withstand considerable disease burden (e.g. white matter lesions, cerebral atrophy) without cognitive impairment (cognitive inefficiency, memory decline). What protects these patients from cognitive impairment? We review the literature on cognitive reserve in MS, which shows that heritable (larger maximal lifetime brain growth) and environmental (greater intellectual enrichment) factors attenuate the negative effect of disease burden on cognitive status. That is, persons with larger maximal lifetime brain growth, greater vocabulary knowledge, and/or greater early life participation in cognitive leisure activities (e.g. reading, hobbies) are better able to cope with MS disease without cognitive impairment. We review evidence that benefits of intellectual enrichment on cognitive status may stem from more efficient patterns of brain function. We discuss clinical implications and highlight important unanswered questions for future research on reserve against cognitive impairment in MS.


An Overview of Nicotinic Cholinergic System Signaling in Neurogenesis.
The production of new neurons continues in the adult mammalian brain because of the sustained proliferation and differentiation of neural stem cells (NSCs) in neurogenic regions. The subventricular zone (SVZ), lining the lateral ventricle, and the subgranular zone (SGZ), which is in the dentate gyrus (DG) of the hippocampus, are the central regions of neurogenesis in the brain. Neurogenesis brings great hope for repairing a damaged brain and motivates researchers to detect the controlling signals of this process. Neurogenesis is regulated by intracellular and extracellular mechanisms that are influenced by neurogenic microenvironments. Recent experimental evidence suggests that the cholinergic system and nicotinic acetylcholine receptors (nAChRs) can directly regulate postnatal neurogenesis via specific mechanisms in these regions. In this review, we outline the cholinergic projections to the neurogenic niches and explain how the cholinergic system may regulate the formation of new neurons. We also discuss the intrinsic signaling pathways by which this system affects neurogenesis.


Intestinal Parasites of Pets and Other House-kept Animals in Moscow.
A study screening pet animals (dogs, cats, chinchillas, ferrets, guinea pigs, rabbits, primates, reptiles, and hedgehogs) within Moscow city limits for intestinal parasitic diseases has been conducted over a period of 6 years. According to the study, parasitic infections caused by intestinal protozoa are found in pet animals more frequently than by intestinal helminths. Although dogs and cats exhibit the highest level of diversity of intestinal parasite species, in the group of exotic animals, helminth infection are found much less frequently and parasitic fauna is represented mostly by intestinal protozoa with a high percentage of mixed infection. The most widespread helminth infeсtion of dogs and cats is toxocarosis (respectively 2.5 and 5.7 %) and the most widespread protozoan infection is Giardia sp. (9.8 and 4.6 %). Giardia sp. was found in 47.4 % of chinchillas, Cryptosporidium sp. was more frequently found in ferrets (6.55 %), protozoa from the family Trichomonadida was found in guinea pigs (9 %), Eimeria sp. in rabbits (13.9 %), Acanthocephala in primates (15.7 %), and eggs from the generaOxyurida (59 %), along with protozoa from the family Trichomonadida, in reptiles. Capillaria sp. was most prevalent in hedgehogs (33.4 %). Acanthocephala eggs, as well as protozoa from the Giardia and Entamoeba genera, were more frequently found in primates. Parasites common to animals and humans, which may become a source of infection for the latter under certain conditions, have been identified in pet animals.


Winter associations predict social and extra-pair mating patterns in a wild songbird.
Despite decades of research, our understanding of the underlying causes of within-population variation in patterns of extra-pair paternity (EPP) remains limited. Previous studies have shown that extra-pair mating decisions are linked to both individual traits and ecological factors. Here, we examine whether social associations among individuals prior to breeding also shape mating patterns, specifically the occurrence of EPP, in a small songbird, the blue tit. We test whether associations during the non-breeding period predict (1) future social pairs, (2) breeding proximity (i.e. the distance between breeding individuals) and (3) the likelihood that individuals have extra-pair young together. Individuals that were more strongly associated (those that foraged more often together) during winter tended to nest closer together. This, by itself, predicts EPP patterns, because most extra-pair sires are close neighbours. However, even after controlling for spatial effects, female-male dyads with stronger social associations prior to breeding were more likely to have extra-pair young. Our findings reveal a carry-over from social associations into future mating decisions. Quantifying the long-term social environment of individuals and studying its dynamics is a promising approach to enhance our understanding of the process of (extra-)pair formation.


On the crumpling of polycrystalline graphene by molecular dynamics simulation.
Crumpled graphene has been emerging as a valuable component for a variety of devices such as supercapacitors or hydrophobic surface coatings due to its geometric change from a 2D to a 3D structure accompanied by changes in its material behavior. As polycrystalline graphene is easier to produce than pristine graphene, certain applications of crumpled graphene may be better suited to polycrystalline graphene. However, the crumpling process of polycrystalline graphene and its relevant mechanical properties remain poorly understood. Here we employ molecular dynamics simulation to model the behavior of polycrystalline graphene under geometric confinement and elucidate the effect of grain size, with a focus on the mechanical stabilizing mechanisms and properties of the crumpled structures in comparison to pristine graphene. Simulation results show that crumpled polycrystalline graphene exhibits a slight negative correlation between average grain size and measured hardness, bulk modulus, and crumpled size. As the size of the grains decreases, the crumpled structures formed are harder and smaller, with sharp edges caused by the grain boundaries. These findings provide evidence towards the feasibility of using polycrystalline graphene in place of pristine graphene in applications involving crumpled carbon structures.


Advanced glycation end products facilitate the proliferation and reduce early apoptosis of cardiac microvascular endothelial cells via PKCβ signaling pathway: Insight from diabetic cardiomyopathy.
To investigate the effects of advanced glycation end products (AGEs) on the proliferation and apoptosis of cardiac microvascular endothelial cells (CMECs) in rats and their underlying signaling pathway. CMECs were isolated from Sprague-Dawley rats. We first examined the effects of AGEs on the proliferation and apoptosis of CMECs and then tested whether protein kinase C (PKC) β blockers could counteract the effects of AGEs. The PKC agonists phorbol 12-myristate 13-acetate (PMA) and PKCβ blockers were also used to verify whether PKC could act independently on CMECs. The receptor for AGEs (RAGE)-small interfering RNA (siRNA) transfection was used to verify the effect of AGEs on PKC. Following the above steps, we explained whether AGEs regulated the CMEC proliferation and early apoptosis through the PKCβ signaling pathway. Proliferation of CMECs was detected using the Cell Counting Kit-8 (CCK-8) assay, and early apoptosis was determined using the Annexin V- Fluorescein Isothiocyanate (FITC)/propidium iodide (PI) double staining. Expression of proliferation and apoptosis-related proteins and PKC phosphorylation were determined by western blotting analysis. Cell cycle distributions were assayed using a BD FACSCalibur cell-sorting system. AGEs facilitated the proliferation of CMECs, upregulated phosphorylated extracellular signal regulated kinase (p-ERK), and accelerated the entry of cells from G1 phase to the S+G2/M phase, which was consistent with the upregulated cyclin D1 by AGEs. AGEs inhibited early apoptosis of CMECs by increasing the expression of survivin and decreasing the expression of cleaved-caspase3. All these effects can be reversed by PKCβ1/2inhibitors. In addition, AGE upregulated the RAGE expression and phosphorylation of PKCβ1/2 in CMECs, while the inhibition of RAGE reversed the phosphorylation, as well as the effects of AGEs on proliferation and apoptosis in CMECs. The study indicated that AGEs facilitated the proliferation and reduced early apoptosis of CMECs via the PKCβ signaling pathway.


Impact of gas(less) laparoscopy and laparotomy on peritoneal tumor growth and abdominal wall metastases.
A tumor model in the rat was used to study peritoneal tumor growth and abdominal wall metastases after carbon dioxide (CO2) pneumoperitoneum, gasless laparoscopy, and laparotomy. The role of laparoscopic resection of cancer is under debate. Insufflation of the peritoneal cavity with CO2 is believed to be a causative factor in the development of abdominal wall metastases after laparoscopic resection of malignant tumors. In the solid tumor model, a lump of 350-mg CC-531 tumor cells was placed intraperitoneally in rats having CO2 pneumoperitoneum (n = 8), gasless laparoscopy (n = 8), or conventional laparotomy (n = 8). After 20 minutes, the solid tumor was removed through a laparoscopic port or through the laparotomy. In the cell seeding model, 5 x 10(5) CC-531 cells were injected intraperitoneally before CO2 pneumoperitoneum (n = 12), gasless laparoscopy (n = 12), or laparotomy (n = 12). All operative procedures lasted 20 minutes. After 6 weeks, in the solid tumor model and after 4 weeks in the cell seeding model, tumor growth was scored semiquantitatively. All results were analyzed using the analysis of variance. In the solid tumor model, peritoneal tumor growth in the laparotomy group was greater than in the CO2 pneumoperitoneum group (p < 0.01). Peritoneal tumor growth in the CO2 group was greater than in the gasless group (p < 0.01). The size of abdominal wall metastases was greater at the port site of extraction of the tumor than at the other port sites (p < 0.001). In the cell seeding model, peritoneal tumor growth was greater after laparotomy in comparison to CO2 pneumoperitoneum (p < 0.02). Peritoneal tumor growth in the CO2 group was greater than in the gasless group (p < 0.01). The port site metastases in the CO2 group were greater than in the gasless group (p < 0.01). The following conclusions can be made: 1) that direct contact between solid tumor and the port site enhances local tumor growth, 2) that laparoscopy is associated with less intraperitoneal tumor growth than laparotomy, and 3) that insufflation of CO2 promotes tumor growth at the peritoneum and is associated with greater abdominal wall metastases than gasless laparoscopy.


The state of prostate MRI in 2013.
Compared with earlier prostate MRI techniques that suffered from relatively poor sensitivity and specificity for detecting prostate cancer because of their reliance predominantly on morphology, multiparametric prostate MRI (mpMRI) in 2013 provides a wealth of functional information that has made possible vastly improved detection and characterization of prostate cancer. Our aims in this article are to describe the various imaging sequences that comprise the mpMRI exam, as well as to review current literature on the strengths/weaknesses of these sequences; to delineate strategies for standardizing interpretation and reporting of MRI results; and finally, to expound on the role that prostate MRI currently does and potentially can play in clinical practice.


[A rare salivary gland neoplasm: cystadenolymphoma].
The authors, after having examined three recent cases, explain some basic concepts about diagnostics and therapy in cystadenolymphoma of salivary glands. As a matter of fact this neoplasia, in spite of its low frequency, is very important because of its still controversial etiopathology and recent tendency in increasing its incidence in females. Today the diagnostic protocol, undertaken after clinical examination, which is necessary, consists of ultrasonography or computerized tomography. But only postoperative histological examination gives a sure diagnosis and can point out main histomorphological characteristics of tumour. Therapeutic approach can be limited to conservative treatment, which is able to respect the parotid gland, its vascularization and innervation.


Specific and non-specific immunity in experimental cryptococcosis in mice.
The course of lethal cryptococcosis in mice was modified by immunization with the same strain or different strains of Cryptococcus neoformans. Protection was associated with a definite decrease in tissue fungus multiplication over the initial 7 days of infection. Such immunity was species-specific and did not protect against heterologous challenge with Staphylococcus aureus, Klebsiella pneumoniae, or Mycobacterium tuberculosis. Similar modification of lethal cryptococcosis was produced by intraperitoneal inoculation of 100 to 200 microg. of Salmonella endotoxin 7 days prior to challenge. In non-specifically (endotoxin) immunized mice there was only a minimal reduction in tissue cryptococcus census during the 1st week of infection. When small numbers of virulent cryptococci were injected intravenously into normal mice, tissue populations rose markedly in all organs studies during the first 7 days. A progressive fall in tissue fungus census was then observed in most mice during the next 6 months. The increase in resistance to cryptococcal challenge following specific immunization, the non-specific protection conferred by injection of bacterial endotoxin and the ability to control and eventually reduce infections with small inocula may well be dependent in each case on the development of specific antibody.


A novel role for 3, 4-dichloropropionanilide (DCPA) in the inhibition of prostate cancer cell migration, proliferation, and hypoxia-inducible factor 1alpha expression.
The amide class compound, 3, 4-dichloropropionanilide (DCPA) is known to affect multiple signaling pathways in lymphocyte and macrophage including the inhibition of NF-kappaB ability. However, little is known about the effect of DCPA in cancer cells. Hypoxia-inducible factor 1 (HIF-1) regulates the expression of many genes including vascular endothelial growth factor (VEGF), heme oxygenase 1, inducible nitric oxide synthase, aldolase, enolase, and lactate dehydrogenase A. HIF-1 expression is associated with tumorigenesis and angiogenesis. We used Transwell assay to study cell migration, and used immunoblotting to study specific protein expression in the cells. In this report, we demonstrate that DCPA inhibited the migration and proliferation of DU145 and PC-3 prostate cancer cells induced by serum, insulin, and insulin-like growth factor I (IGF-I). We found that DCPA inhibited HIF-1 expression in a subunit-specific manner in these cancer cell lines induced by serum and growth factors, and decreased HIF-1alpha expression by affecting its protein stability. DCPA can inhibit prostate cancer cell migration, proliferation, and HIF-1alpha expression, suggesting that DCPA could be potentially used for therapeutic purpose for prostate cancer in the future.


Multiple levels of linguistic and paralinguistic features contribute to voice recognition.
Voice or speaker recognition is critical in a wide variety of social contexts. In this study, we investigated the contributions of acoustic, phonological, lexical, and semantic information toward voice recognition. Native English speaking participants were trained to recognize five speakers in five conditions: non-speech, Mandarin, German, pseudo-English, and English. We showed that voice recognition significantly improved as more information became available, from purely acoustic features in non-speech to additional phonological information varying in familiarity. Moreover, we found that the recognition performance is transferable between training and testing in phonologically familiar conditions (German, pseudo-English, and English), but not in unfamiliar (Mandarin) or non-speech conditions. These results provide evidence suggesting that bottom-up acoustic analysis and top-down influence from phonological processing collaboratively govern voice recognition.


Treating hypertension to prevent coronary disease.
Because most patients with mild to moderate hypertension will not suffer a cardiovascular event due to elevated blood pressure, the presence of other risk factors must be assessed. Many of these are alterable with nondrug therapies, which cost little and carry no risks if applied sensibly. Drug therapies have costs, discomforts, and risks and should be used only for those at high risk or those who fail to respond adequately to nondrug therapies. When drug therapy is necessary, start with low doses and aim for a slow reduction of blood pressure, avoiding hypoperfusion and reducing as many risk factors as possible. Alpha blockers, angiotensin-converting enzyme inhibitors, and calcium-channel blockers may avoid metabolic risks associated with high-dose diuretic and beta-blocker therapy. The establishment of therapeutic goals, individualized assessment of status, and a conservative approach to treatment are the basis for optimal management of patients with hypertension.


Assessment of patient simulation use in selected baccalaureate nursing programs in the United States.
Newly graduated nurses are expected to possess clinical skills and the ability to critically judge quality in patient care. There are an increasing number of baccalaureate nursing (BSN) schools that are integrating the use of patient simulation (PS) in the educational experience of their students. This descriptive study examines the use of PS technology in selected BSN programs in the United States. This study targeted National League for Nursing-accredited BSN schools with an online survey related to the current use of PS in course curriculum and how it is being used. Two hundred nine BSN schools were identified and 78 schools responded (37.3% response rate). Sixty (78.9%) BSN schools responded to the survey reported using patient simulators in core clinical nursing courses: health assessment, nursing fundamentals, medical/surgical nursing I and II, pediatrics, and obstetrics courses. Approximately 31% of schools reported using high-fidelity scenarios in more than 51% of their clinical courses. The responding schools indicate that they are using PS in the usual undergraduate nursing courses that coincide with clinical settings. The replacement of actual clinical hours with PS remains controversial and unresolved. Responses to an open-ended question indicated interest in using PS but that many schools are limited by not having a dedicated faculty to champion the way and resources to purchase the technology. Although there were limitations to this study, it is one of the first to describe the patterns of using PS in nursing schools for clinical education. As the use of this technology grows in BSN programs, addressing the issues resulting from this study are essential to understanding the use of this technology in nursing education.


What does a trainee see?
The experience of a trainee was documented in detail for a complete training year and the data were stored and analysed using a suite of purpose-written computer programs. The results indicate that the experience of the trainee was extremely similar to that of the trainer and that continuity of care must be considered in planning a training programme. The findings also emphasize that general practice deals with a wide range of problems many of which occur infrequently and therefore may not be adequately covered during the training year.


[Clinical justification of medico-psychological care to the victims of technogenic accidents and catastrophes with prevalence of anxious and depressive symptoms of non-psychotic register].
In the article the clinical justification of medico-psychological care to the victims of technogenic accidents and catastrophes with prevalence of anxious and depressive symptoms of non-psychotic register is described. The necessity of differentiated approach is analyzed in accomplishing of psychotherapy of this contingent of patients taking into account the high level of anxiety, emotional stress, decreased mood, low levels of the quality of life in the remote period of strong stressful factor's action.


Ophthalmology consultation in the diagnosis and treatment of sarcoidosis.
We reviewed 204 cases of biopsy-proved sarcoidosis at our institution from 1967 through 1983 to determine the extent of this disease in our catchment area and the degree of awareness by the various medical specialties of sarcoid manifestations. The ophthalmology service was used as an example. Our results showed that there were familial clusters of sarcoid; that one half of the patients born in the United States were from the southeast; that the mode of initial presentation varied considerably; and that only 44% of patients were referred to an ophthalmologist even though more than one half of those examined by an eye doctor manifested signs and symptoms of ocular sarcoidosis. We advocate a more cooperative interdisciplinary approach to the diagnosis and treatment of sarcoidosis because of its broad spectrum of clinical manifestations.


Radar walk detection in the apartments of elderly.
Seniors want to live more independent lifestyles. This comes with some risks including dwindling health and major injuries due to falling. A factor that has been studied and seen to have a correlation to fall risk is change in gait speed. Our goal is to create a passive system that monitors the gait of elderly so that assessments can be given by caregivers if gait changes do occur. This paper will cover a method of using pulse-Doppler radar to detect when walks occur. In unscripted living environments, we are able to detect valid walks. The system does miss walks during the day, but when walks are detected, they are actually valid walks 91.8% of the time using a large data base of radar signals captured in living environments.


Coexistence of primary adenocarcinoma of the lung and Tsukamurella infection: a case report and review of the literature.
A major diagnostic challenge in the evaluation of a cavitary lung lesion is to distinguish between infectious and malignant etiologies. We present the case of an elderly man presenting with fever, hemoptysis and a left upper lobe cavitary lesion. Serial sputum cultures grew Tsukamurella pulmonis, a rare pathogen associated with cavitary pneumonia in immunocompromised patients. However, despite clinical improvement with antibiotic therapy targeted to the organism, concomitant discovery of a papillary thyroid carcinoma led to a needle biopsy of the cavitary lesion, which showed evidence of primary lung adenocarcinoma. This is the first description of Tsukamurella infection in the setting of primary lung carcinoma. The report also illustrates the potential complex nature of cavitary lesions and emphasizes the need to consider the coexistence of malignant and infectious processes in all patients, especially those with risk factors for malignancy that fail to improve on antibiotic therapy.


Brain distribution and fate of tris(2-chloroethyl) phosphate in Fischer 344 rats.
Tris(2-chloroethyl) phosphate (TRCP) is a flame retardant that has a wide variety of industrial applications. In subchronic studies, oral administration of TRCP to rats and mice has been reported to produce dose-, sex-, and species-dependent lesions in the hippocampal brain region. The present investigation has examined the metabolism, elimination, and regional brain distribution of [14C]TRCP in male and female rats. [14C]TRCP was administered by gavage (0, 175, 350, or 700 mg/kg) and urine, feces, exhaled volatiles, CO2, and selected tissues were collected. Regional brain distribution of 14C was determined 2 hr following single doses of TRCP to male and female rats, and 24 hr after a single dose and the last of 14 daily doses of TRCP to female rats. Results of these studies indicate that TRCP is readily absorbed from the gastrointestinal tract, distributed to all brain regions, and that metabolism and excretion are nearly complete in 72 hr. Most of the TRCP-derived radioactivity was excreted in urine (up to 85%), with feces, volatiles, and CO2 combined accounting for less than 10% of the dose. Predominant signs of toxicity associated with TRCP administration (350 and 700 mg/kg) were seizures within 2 hr of treatment, when most of the TRCP-derived radioactivity present in brain tissue was in the form of the parent compound. Traces of inextractable 14C were detected at later times, but this material was not concentrated in brain relative to other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)


Serum inducible protein 10 kDa/C-X-C motif chemokine 10 levels predict regression of M2BPGi-based liver fibrosis after hepatitis C virus eradication by direct-acting antiviral agents.
It is desirable to identify predictors of regression of liver fibrosis after achieving sustained virological response by anti-hepatitis C virus (anti-HCV) therapy. We retrospectively investigated the serum interferon-γ inducible protein 10 kDa (IP-10) level as a predictive indicator of regression of liver fibrosis after successful hepatitis C virus eradication by direct-acting antiviral agents (DAAs) therapy. The study participants were recruited from a historical cohort of 116 chronically hepatitis C virus-infected patients who had achieved sustained virological response by DAAs therapy and whose serum Mac-2 binding protein glycosylation isomer (M2BPGi) levels at baseline (before DAAs therapy) were ≥2.0 cut-off index. We defined patients with M2BPGi levels <1.76 and ≥1.76 cut-off index at 2 years after the end of treatment (EOT) as the regression (n = 71) and non-regression (n = 45) groups, respectively. Multivariate analyses revealed that the albumin-bilirubin score at baseline, and albumin-bilirubin score, Fibrosis-4 index at 24 weeks after the EOT, and serum IP-10 change from baseline to 24 weeks after the EOT (IP-10 change) were significantly associated with regression of M2BPGi-based liver fibrosis. In addition, IP-10 change was significantly associated with regression of M2BPGi-based liver fibrosis by a multivariate analysis, even when the serum M2BPGi levels were aligned by propensity score matching and in patients with advanced M2BPGi-based liver fibrosis: M2BPGi levels ≥3.3 cut-off index at baseline. Serum IP-10 change from baseline to 24 weeks after the EOT is a feasible predictor of regression of M2BPGi-based liver fibrosis after achieving sustained virological response with DAA therapy.


Early presentation of buried bumper syndrome.
Percutaneous endoscopic gastrostomy (PEG) is a relatively safe and effective method of providing nutrition to patients with neurologic deficits or proximal gastrointestinal pathology. Complications that follow this common procedure include dislodgement, dysfunction, infection and aspiration. The "Buried Bumper Syndrome" (BBS) is an infrequent and late complication of PEG tubes that can result in tube dysfunction, gastric perforation, bleeding, peritonitis or death. The emergency physician should be aware of historical and exam features that suggest BBS and distinguish it from other, more benign, PEG-tube related complaints. We report a case of a woman presenting with BBS 3 weeks after having a PEG tube placed.


Neutrophil-targeted combinatorial nanosystems for suppressing bacteremia-associated hyperinflammation and MRSA infection to improve survival rates.
There is currently no specific and effective treatment for bacteremia-mediated sepsis. Hence, this study engineered a combinatorial nanosystem containing neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles to enable the dual mitigation of bacteremia-associated inflammation and methicillin-resistant Staphylococcus aureus (MRSA) infection. The targeted nanoparticles were developed by conjugating anti-lymphocyte antigen 6 complex locus G6D (Ly6G) antibody fragment on the nanoparticulate surface. The particle size and zeta potential of the as-prepared nanosystem were about 200 nm and -25 mV, respectively. The antibody-conjugated nanoparticles showed a three-fold increase in neutrophil internalization compared to the unfunctionalized nanoparticles. As a selective phosphodiesterase (PDE) 4 inhibitor, the roflumilast in the nanocarriers largely inhibited cytokine/chemokine release from the activated neutrophils. The fusidic acid-loaded nanocarriers were vital to eliminate biofilm MRSA colony by 3 log units. The nanoparticles drastically decreased the intracellular bacterial count compared to the free antibiotic. The in vivo mouse bioimaging demonstrated prolonged retention of the nanosystem in the circulation with limited organ distribution and liver metabolism. In the mouse bacteremia model, the multifunctional nanosystem produced a 1‒2 log reduction of MRSA burden in peripheral organs and blood. The functionalized nanosystem arrested the cytokine/chemokine overexpression greater than the unfunctionalized nanocarriers and free drugs. The combinatory nanosystem also extended the median survival time from 50 to 103 h. No toxicity from the nanoformulation was found based on histology and serum biochemistry. Furthermore, our data proved that the active neutrophil targeting by the versatile nanosystem efficiently alleviated MRSA infection and organ dysfunction caused by bacteremia. STATEMENT OF SIGNIFICANCE: Bacteremia-mediated sepsis poses a significant challenge in clinical practice, as there is currently no specific and effective treatment available. In our study, we have developed a novel combinatorial nanosystem to address this issue. Our nanosystem consists of neutrophil-targeted roflumilast-loaded nanocarriers and non-targeted fusidic acid-loaded nanoparticles, enabling the simultaneous mitigation of bacteremia-associated inflammation and MRSA infection. Our nanosystem demonstrated the decreased neutrophil activation, effective inhibition of cytokine release, elimination of MRSA biofilm colonies, and reduced intracellular bacterial counts. In vivo experiments showed prolonged circulation, limited organ distribution, and increased survival rates in a mouse bacteremia model. Importantly, our nanosystem exhibited no toxicity based on comprehensive assessments.


Estrogen and progestin receptors appear in transplanted fetal hypothalamus-preoptic area independently of the steroid environment.
Sexual maturation and differentiation of the rat brain are believed to result from the interaction of gonadal steroids with specific neural receptors during late fetal and early postnatal life. A variety of evidence indicates that the first appearance of estrogen receptors in the hypothalamus-preoptic area (HPOA) during the perinatal period is a crucial evident underlying these processes. However, it is unknown to what extent the ontogeny of estrogen receptors is itself influenced by gonadal steroids present in the fetal environment. In order to address this question, estrogen receptors were assayed in HPOA 8 weeks after transplantation of the tissue from embryonic day 15 to 18 fetuses to either the choroidal pia overlying the superior colliculus or to the anterior chamber of the eye of adult female hosts. Host animals were either intact or ovariectomized and adrenalectomized, with or without estrogen replacement. The saturable binding of estradiol to cytosol of HPOA transplants exhibited the steroid specificity and high affinity characteristic of authentic estrogen receptors. No differences in the level of cytosol estrogen receptors in transplanted HPOA grown in the presence or absence of gonadal steroids were found. Receptor concentrations were also similar in HPOA taken from male or female fetuses. Autoradiography with [3H]estradiol revealed clusters of estrophilic cells in the transplants similar to those of the adult host hypothalamus, again regardless of whether the transplant developed in the presence of gonadal steroids. Estrogen receptors from both groups were also found to be biochemically functional as indicated by the ability of acute estrogen treatment to induce progestin receptors in the transplants.(ABSTRACT TRUNCATED AT 250 WORDS)


Helping individuals in the sex trade during COVID-19: The perspectives of Israeli aid organizations.
The coronavirus disease (COVID-19) pandemic has had a collateral effect on marginalized populations, including individuals in the sex trade (IST). In addition, the literature of the past year has documented a significant impact of the pandemic on healthcare providers. However, there is a lack of research on the new challenges and existing hardships facing aid organizations working with IST populations. This naturalistic qualitative study used semi-structured interviews with 33 IST aid organization workers in Israel between May and July 2020 to capture their perceptions and experiences within broader social-relational contexts. Data analysis revealed that the pandemic impacted three different arenas: The assistance systems and the quality of care; The relationship between aid organizations and state authorities; and The intraorganizational and interorganizational relationship. These findings add to the knowledge about the impacts of the COVID-19 pandemic on aid organizations, particularly the need for greater collaboration between aid organizations during health crises and governmental support for these organizations. In addition, the study highlights the opportunities that a global and local health crisis can create advancing new knowledge and practices used by aid organizations in their work to assist IST populations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Technology of vitamins containing double layer suppositories].
At present ascorbic acid and cyanocobalamin are widely used in medical practice. Often they are administered simultaneously; chemically they are incompatible, as ascorbic acid (redox compound) inactivates cyanocobalamin. The combination of ascorbic acid and cyanocobalamin is the problem of pharmacy. To solve the problem double-layer suppositories containing two incompatible vitamins: ascorbic acid and cyanocobalamin were developed. Pharmaceutical bioavailability of ascorbic acid and cyanocobalamin has been studied using in-vitro methods to develop optimal base for suppositories. As a result of investigations optimal composition and technology of the double-layer suppositories containing ascorbic acid and cyanocobalamin which met requirements has been developed. Sequential release of active compounds and as a result - sequential pharmacologic action is achieved.


Capillary Wicking in Hierarchically Textured Copper Nanowire Arrays.
Capillary wicking through homogeneous porous media remains challenging to simultaneously optimize due to the unique transport phenomena that occur at different length scales. This challenge may be overcome by introducing hierarchical porous media, which combine tailored morphologies across multiple length scales to design for the individual transport mechanisms. Here, we fabricate hierarchical nanowire arrays consisting of vertically aligned copper nanowires (∼100 to 1000 nm length scale) decorated with dense copper oxide nanostructures (∼10 to 100 nm length scale) to create unique property sets that include a large specific surface area, high rates of fluid delivery, and the structural flexibility of vertical arrays. These hierarchical nanowire arrays possess enhanced capillary wicking ( K/ Reff = 0.004-0.023 μm) by utilizing hemispreading and are advantageous as evaporation surfaces. With the advent and acceleration of flexible electronics technologies, we measure the capillary properties of our freestanding hierarchical nanowire arrays installed on curved surfaces and observe comparable fluid delivery to flat arrays, showing the difference of 10-20%. The degree of effective inter-nanowire pore and porosity is shown to govern the capillary performance parameters, thereby this study provides the design strategy for capillary wicking materials with unique and tailored combinations of thermofluidic properties.


Complications of systemic corticosteroid therapy for problematic hemangioma.
Systemic corticosteroid therapy has been used to treat hemangiomas for 30 years; yet, there are no studies of possible complications. We reviewed the database of the Vascular Anomalies Center at the Boston Children's Hospital and gathered information on short- and long-term side effects in children who were given systemic corticosteroids for problematic hemangiomas. In addition, a questionnaire regarding early and late consequences was sent to the families of children who were treated with corticosteroids from 1983 to 1997. Of 300 patients with hemangiomas, 80 children were identified as having received a full course of systemic corticosteroids for problematic tumors. Complete data were collected on 62 of these children. The response rate to the questionnaire was 78 percent (n = 62 of 80). The initial dose of corticosteroid varied from 2 to 3 mg/kg/ day. Duration of therapy ranged from 2 to 21 months (mean, 7.9 months; median, 6.5 months). The follow-up interval from the cessation of therapy ranged from 6 months to 15 years (mean, 4 years; median, 3 years). Short-term complications included cushingoid facies (n = 44; 71 percent), personality changes (n = 18; 29 percent), gastric irritation (n = 13; 21 percent), fungal (oral or perineal) infection (n = 4; 6 percent), and diminished gain of height (n = 22; 35 percent) and weight (n = 26; 42 percent). A total of 91 percent of children who had diminished gain of height (n = 20) returned to their pretreatment growth curve for height by 24 months of age. One child, who was treated at another institution with a dose of 20 mg/kg/day for 6.5 months that was slowly tapered over 18 months, was petite 6 years after ending therapy. Another child treated with an initial dose of 2 mg/kg/day for 5 months was smaller than predicted at the age of 6 years, but she was born prematurely and was on ventilatory support for respiratory distress. Three children treated with the standard dose and duration were at a low percentile for weight 4, 5, and 10 years after the cessation of therapy. Statistical analysis showed a correlation between diminished gain of height with duration of therapy and age at initiation of treatment. One child had corticosteroid myopathy that resolved with cessation of therapy. We found no evidence for immunologic suppression, i.e., there was no increase in the number of bacterial infections during corticosteroid administration. In conclusion, systemic corticosteroids can be safely given to treat endangering hemangiomas in infants at doses of 2 to 3 mg/kg/day, which are slowly tapered and stopped before the age of 1 year. Short-term side effects were minor and transient, and no serious long-term complications occurred.


PTPN11 induces endoplasmic stress and apoptosis in SH-SY5Y cells.
PTPN11 is associated with regulation of growth factor signaling pathways in neuronal cells. Using SH-SY5Y neuroblastoma cells, we showed that adeno-associated virus (AAV)-mediated PTPN11 upregulation was associated with TrkB antagonism, reduced neuritogenesis and enhanced endoplasmic reticulum (ER) stress response leading to apoptotic changes. Genetic knock-down of PTPN11 on the other hand leads to increased TrkB phosphorylation in SH-SY5Y cells. ER stress response induced by PTPN11 upregulation was alleviated pharmacologically by a TrkB agonist. Conversely the enhanced ER stress response induced by TrkB receptor antagonism was ameliorated by PTPN11 suppression, providing evidence of cross-talk of PTPN11 effects with TrkB actions. BDNF treatment of neuronal cells with PTPN11 upregulation also resulted in reduced expression of ER stress protein markers. This study provides evidence of molecular interactions between PTPN11 and the TrkB receptor in SH-SY5Y cells. The results reinforce the role played by PTPN11 in regulating neurotrophin protective signaling in neuronal cells and highlight that PTPN11 dysregulation promotes apoptotic activation. Based on these findings we suggest that blocking PTPN11 could have potential beneficial effects to limit the progression of neuronal loss in neurodegenerative disorders.


Paramedic Intubation Experience Is Associated With Successful Tube Placement but Not Cardiac Arrest Survival.
Paramedic experience with intubation may be an important factor in skill performance and patient outcomes. Our objective is to examine the association between previous intubation experience and successful intubation. In a subcohort of out-of-hospital cardiac arrest cases, we also measure the association between patient survival and previous paramedic intubation experience. We analyzed data from Ambulance Victoria electronic patient care records and the Victorian Ambulance Cardiac Arrest Registry for January 1, 2008, to September 26, 2014. For each patient case, we defined intubation experience as the number of intubations attempted by each paramedic in the previous 3 years. Using logistic regression, we estimated the association between intubation experience and (1) successful intubation and (2) first-pass success. In the out-of-hospital cardiac arrest cohort, we determined the association between previous intubation experience and patient survival. During the 6.7-year study period, 769 paramedics attempted intubation in 14,857 patients. Paramedics typically performed 3 intubations per year (interquartile range 1 to 6). Most intubations were successful (95%), including 80% on the first attempt. Previous intubation experience was associated with intubation success (odds ratio 1.04; 95% confidence interval 1.03 to 1.05) and intubation first-pass success (odds ratio 1.02; 95% confidence interval 1.01 to 1.03). In the out-of-hospital cardiac arrest subcohort (n=9,751), paramedic intubation experience was not associated with patient survival. Paramedics in this Australian cohort performed few intubations. Previous experience was associated with successful intubation. Among out-of-hospital cardiac arrest patients for whom intubation was attempted, previous paramedic intubation experience was not associated with patient survival.


Gonadotropin-releasing hormone gene expression during the rat estrous cycle: effects of pentobarbital and ovarian steroids.
Although hypothalamic GnRH release is known to be modulated by neural and hormonal factors, the relationship between altered GnRH secretion and GnRH synthesis remains unclear. In an attempt to address this question, we examined GnRH gene expression in the rat hypothalamus using in situ hybridization histochemistry. An 25S-labeled antisense RNA probe was used to identify neurons expressing GnRH mRNA in an area that included the diagonal band of Broca, the organum vasculosum of the lamina terminalis, and the preoptic area. The number of GnRH mRNA-expressing cells was determined at various times during the rat estrous cycle. During proestrus, the number of GnRH mRNA-expressing cells decreased somewhat at 1400-1600 h, increased significantly at 1800 h (the time of the LH surge), then gradually returned to basal levels at 2200 h. Expression did not change substantially at other times during the estrous cycle. To understand this close temporal relationship between the LH surge and increased GnRH mRNA levels, we examined GnRH gene expression in proestrous animals in which the LH surge was blocked with pentobarbital. Pentobarbital treatment blocked the increase in the number of GnRH mRNA-expressing cells normally observed at 1800 h in saline-treated controls, suggesting that the increase in GnRH gene expression is closely coupled to secretion of GnRH from the hypothalamus. Finally, we addressed the question of whether ovarian steroids have direct effects on GnRH gene expression by examining GnRH mRNA levels in ovariectomized steroid-treated rats at a time before (1100 h) and a time after (1800 h) hypothalamic GnRH hypersecretion. At 1100 h, no significant changes were observed, but at 1800 h, estrogen-treated rats showed a significant increase in both the number of GnRH mRNA-expressing cells and serum LH levels. This suggests that estrogen influences GnRH gene expression indirectly, perhaps by altering hypothalamic GnRH release. Our results in each of these models suggest that GnRH mRNA levels increase in response to GnRH hypersecretion at the time of the LH surge.


Detection of somatic DNA recombination in the transgenic mouse brain.
A DNA construct containing the bacterial beta-galactosidase gene (lacZ) was used to study somatic DNA recombination in the transgenic mouse brain. Recombination-positive areas of the adult brain were stained blue with X-gal, a substrate of beta-galactosidase. Blue-colored cells appeared soon after birth, and continued to emerge in postnatal tissue. Staining was prominent in sensory as opposed to motor regions of the brain, and was present in more than 70 discrete areas of the nervous system. The possibility of DNA rearrangement is discussed with respect to the development of the central nervous system.


[Diagnosis, epidemiology and comorbidity of anxiety disorders].
Fears and apprehensions which significantly impair a person's everyday life and which cannot be attributed to an organic brain disturbance or to other mental disorders or physical problems are grouped together in the class of "anxiety disorders". Three types of anxiety disorders can be distinguished on the basis of clinical picture and the course of development of symptoms: phobias, panic disorder and generalized anxiety disorder. Recent epidemiological studies indicate that anxiety disorders are one of the most common kinds of mental disorder. More than a fourth of the persons surveyed in a general population have suffered from an anxiety disorder at some point in their lives. Phobias occur most frequently, with social phobias being the most common according to the latest studies (lifetime prevalence of 13.3% to 16%). The lifetime prevalence of panic disorder is estimated at 1.2% to 3.5%, depending on the diagnostic system (DSM-III-R, ICD-10) and survey instruments used. Generalized anxiety disorder is estimated to have a lifetime prevalence of between 1.9% and 6.6%. Overall, anxiety disorders tend to occur more often in women than in men. Onset is usually in childhood or adolescence. All anxiety disorders have a high lifetime comorbidity with other mental disorders. The frequency of anxiety disorders occurring in combination with affective disorders and substance abuse and dependence over the span of a lifetime is significantly high. Increased risk of suicide is an important factor to consider when assessing these patients, especially in the case of panic disorder or social phobias.


Role of SCCmec type in resistance to the synergistic activity of oxacillin and cefoxitin in MRSA.
β-lactam antibiotics target penicillin-binding proteins (PBPs) preventing peptidoglycan synthesis and this inhibition is circumvented in methicillin resistant Staphylococcus aureus (MRSA) strains through the expression of an additional PBP, named PBP2A. This enzyme is encoded by the mecA gene located within the Staphylococcal Chromosome Cassette mec (SCCmec) mobile genetic element, of which there are 12 types described to date. Previous investigations aimed at analysing the synergistic activity of two β-lactams, oxacillin and cefoxitin, found that SCCmec type IV community-acquired MRSA strains exhibited increased susceptibility to oxacillin in the presence of cefoxitin, while hospital-acquired MRSA strains were unaffected. However, it is not clear if these differences in β-lactam resistance are indeed a consequence of the presence of the different SCCmec types. To address this question, we have exchanged the SCCmec type I in COL (HA-MRSA) for the SCCmec type IV from MW2 (CA-MRSA). This exchange did not decrease the resistance of COL against oxacillin and cefoxitin, as observed in MW2, indicating that genetic features residing outside of the SCCmec element are likely to be responsible for the discrepancy in oxacillin and cefoxitin synergy against these MRSA strains.


Exercise-Induced Reductive Stress Is a Protective Mechanism against Oxidative Stress in Peripheral Blood Mononuclear Cells.
Eccentric exercise is a well-studied modality that induces oxidative stress and muscle damage. Furthermore, it promotes inflammatory response in which peripheral blood mononuclear cells (PBMCs) are the major mediators. Although free radicals are necessary in a specific range of concentrations, yet unknown, it remains unclear whether reductive redox status (i.e., increased antioxidant defenses and impaired free radical generation) is beneficial or not. Thus, the aim of the present investigation was to examine the effects of reductive stress and the impact of reduced glutathione (GSH) baseline values on the ability of PBMCs to counteract oxidative stress induced by a potent oxidative agent. PBMCs were isolated from the blood of subjects who performed eccentric exercise and treated with t-BOOH for 24 h. The subjects were clustered in the reductive and the oxidative group on the basis of increased or decreased GSH concentration postexercise compared to preexercise values, respectively. According to our results in PBMCs, lipid peroxidation levels as depicted by thiobarbituric acid reactive substances (TBARS) remained unchanged in the reductive group contrary to the observed enhancement in the oxidative group. In addition, GSH concentration and catalase activity increased in the reductive group, whereas they were not affected in the oxidative group. In conclusion, the effects of an oxidizing agent on the redox status of PBMCs isolated from the blood of athletes after acute eccentric exercise are dependent on the baseline values of GSH in erythrocytes. Otherwise, reductive stress defined by increased GSH levels is a protective mechanism, at least when followed by an oxidative stimulus.


Reasons individuals stop eating questionnaire (RISE-Q) among adults in the United Arab Emirates.
The relationship between obesity and satiation is complex and bidirectional. Understanding differences in reasons for meal termination may enhance our understanding of overeating risks and susceptibility to overconsumption. This study aimed to investigate the reasons why individuals in the UAE stop eating. A cross-sectional web-based study was conducted among adults ≥18 years in the UAE (n = 1482). Using a self-administered online questionnaire, we collected information on sociodemographic characteristics, lifestyle habits, and eating behavior using the Reasons Individuals Stop Eating-Questionnaire (RISE-Q-15) used twice for breakfast/main meal. The items were categorized into five scales; decreased food appeal (DFA), physical satisfaction (PS), planned amount (PA), self-consciousness (SC), and decreased priority of eating (DPE). All items were scored from 1 to 7 ranging between 3 to 21 on each scale. A paired t-test was used to evaluate the difference between the RISE-Q scores on each scale concerning the two meals. The main reason why participants stopped eating breakfast was under the PS scale (14.91 ± 3.72), followed by the PA scale (14.58 ± 3.00). The main reason why participants stopped eating main meals was under the PS scale (14.78 ± 3.56), followed by the PA scale (14.77 ± 43.81). The mean score of the DPE scale was significantly higher for breakfast than the main meal (p = 0.038). More than half of the participants reported an average eating rate (58.7%). Pearson's chi-square analysis revealed that the eating rate was dependent on BMI (p<0.001). Considering individual mealtimes and addressing factors related to PS and PA of food is crucial when designing nutrition interventions aiming to promote healthy eating habits among adults in the UAE.


Posttranscriptional upregulation by microRNAs.
MicroRNAs are small non-coding RNA guide molecules that regulate gene expression via association with effector complexes and sequence-specific recognition of target sites on other RNAs; misregulated microRNA expression and functions are linked to a variety of tumors, developmental disorders, and immune disease. MicroRNAs have primarily been demonstrated to mediate posttranscriptional downregulation of expression; translational repression, and deadenylation-dependent decay of messages through partially complementary microRNA target sites in mRNA untranslated regions (UTRs). However, an emerging assortment of studies, discussed in this review, reveal that microRNAs and their associated protein complexes (microribonucleoproteins or microRNPs) can additionally function to posttranscriptionally stimulate gene expression by direct and indirect mechanisms. These reports indicate that microRNA-mediated effects can be selective, regulated by the RNA sequence context, and associated with RNP factors and cellular conditions. Like repression, translation upregulation by microRNAs has been observed to range from fine-tuning effects to significant alterations in expression. These studies uncover remarkable, new abilities of microRNAs and associated microRNPs in gene expression control and underscore the importance of regulation, in cis and trans, in directing appropriate microRNP responses.


Universal impulse noise filter based on genetic programming.
In this paper, we present a novel method for impulse noise filter construction, based on the switching scheme with two cascaded detectors and two corresponding estimators. Genetic programming as a supervised learning algorithm is employed for building two detectors with complementary characteristics. The first detector identifies the majority of noisy pixels. The second detector searches for the remaining noise missed by the first detector, usually hidden in image details or with amplitudes close to its local neighborhood. Both detectors are based on the robust estimators of location and scale-median and MAD. The filter made by the proposed method is capable of effectively suppressing all kinds of impulse noise, in contrast to many existing filters which are specialized only for a particular noise model. In addition, we propose the usage of a new impulse noise model-the mixed impulse noise, which is more realistic and harder to treat than existing impulse noise models. The proposed model is the combination of commonly used noise models: salt-and-pepper and uniform impulse noise models. Simulation results show that the proposed two-stage GP filter produces excellent results and outperforms existing state-of-the-art filters.


Color difference formulas and visual acceptability.
Several color difference formulas were examined with the data by Davidson and Friede and by Thurner and Walther. The correlation between formulas and visual assessment is only moderate. The differences in the correlations of the individual formulas are too slight to give a reliable answer to the question which of the formulas are superior to the others. It is also still an open matter whether a formula is superior to the judgement by an average observer. Besides possible unreliabilities in the data there may be a fundamental difference between acceptability and perceptibility. New and very extensive investigations are therefore necessary.


Involvement of PEG-carboxylate dehydrogenase and glutathione S-transferase in PEG metabolism by Sphingopyxis macrogoltabida strain 103.
Sphingopyxis terrae and the Sphingopyxis macrogoltabida strains 103 and 203 are able to degrade polyethylene glycol (PEG). They possess the peg operon, which is responsible for the conversion of PEG to PEG-carboxylate-coenzyme A (CoA). The upstream (3.0 kb) and downstream (6.5 kb) regions of the operon in strain 103 were cloned and sequenced. The structure was well conserved between S. macrogoltabida strain 203 and S. terrae, except that two sets of transposases are absent in strain 203. The downstream region contains the genes for PEG-carboxylate dehydrogenase (PCDH), glutathione S-transferase (GST), tautomerase, and a hypothetical protein. The genes for pcdh and gst were transcribed constitutively and monocistronically, indicating that their transcription is independent of the operon regulation. PCDH and GST were expressed in Escherichia coli and characterized biochemically. PCDH is a homotetramer of 64-kDa subunits and contains one molecule of flavin adenine dinucleotide per subunit. The enzyme dehydrogenates PEG-carboxylate to yield glyoxylate, suggesting that the enzyme is the third enzyme involved in PEG degradation. GST is a homodimer of 28-kDa subunits. GST activity was noncompetitively inhibited by acyl-CoA and PEG-carboxylate-CoA, suggesting the interaction of GST with them. The proposed role for GST is to buffer the toxicity of PEG-carboxylate-CoA.


Isolation and characterization of the goldfish thyrotropin beta subunit gene including the 5'-flanking region.
The complete gene encoding the beta subunit of thyrotropin (thyroid-stimulating hormone, TSH) was isolated from a goldfish genomic library. The goldfish TSHbeta subunit gene, which is approximately 2.0 kilobase pairs (kb) in length, consisted of three exons and two introns. The first intron was much longer (0.89 kb) than the second intron (0.3 kb) as are TSHbeta genes in mammalian species. On the basis of the location of the first intron, the goldfish TSHbeta gene belongs to the mammalian TSHbeta/FSHbeta gene group, which is distinct from the LHbeta group. Inspection of the 5'-flanking and exon 1 regions of the goldfish TSHbeta gene (1.2 kb) revealed the presence of several putative cis-acting elements, including the negative triiodothyronine (T(3))-responsive element (nTRE), Pit-1 element, and GATA-2 element. Comparison of the goldfish sequence with mammalian TSHbeta promoter sequences showed an identical region, nTRE, in the first exon-intron junction region. An in vitro study using dispersed goldfish pituitary cells showed that T(3) treatment (20 ng/ml) suppressed the TSHbeta mRNA level in the cells. These data indicate that (1) the basic structure of TSHbeta genes is highly conserved in vertebrates and that (2) T(3) acts directly on the pituitary and inhibits TSHbeta gene expression in goldfish, probably via the nTRE in the TSHbeta gene.


Perimetric severity in hospital-based and population-based glaucoma patients.
The aim was to compare the severity of glaucoma among newly diagnosed patients presenting to a hospital-based glaucoma care centre (HBGS: Sankara Nethralaya, Medical Research Foundation) with that of age matched subjects from the population-based Chennai Glaucoma Follow-up Study (CGFS). Newly diagnosed subjects with primary glaucoma from HBGS and age- and gender-matched subjects from the urban arm of CGFS examined during the same time period were included. All subjects underwent comprehensive ocular examinations including Humphrey visual field (HVF: 24-2 SITA Standard). Glaucoma was defined as: an intraocular pressure (IOP) of 22 or greater mmHg in either eye; vertical cup-to-disc ratio (VCDR) of 0.7 or greater or asymmetry 0.2 or more or the presence of focal thinning, notching or a splinter haemorrhage. All subjects had a minimum of three follow-up visits and reliable visual fields. The IOP, vertical cup-to-disc ratio, mean deviation (MD) and pattern standard deviation (PSD) of the Humphrey field measurements at the third follow-up visit of CGFS were compared for assessing the severity of glaucoma with the HBGS group. Forty-seven age-matched subjects from both the study populations were selected. Significantly higher (p = 0.04) IOP was noted in the HBGS population than the CGFS, with a difference in mean IOP of 2.80 mmHg (95% CI of diff: 0.14 to 5.46). The mean ± SD of the mean deviation and pattern standard deviation were -6.92 ± 6.53 dB and 6.05 ± 4.20 dB among the HBGS and -4.47 ± 4.19 dB and 3.26 ± 2.69 dB among the CGFS population, respectively, the difference in the mean deviation (p = 0.036) and pattern standard deviation (p = 0.0001) were statistically significant. The mean vertical cup-to-disc ratio did not vary between populations (p = 0.14). Patients from the HBGS group had higher IOP and more severe visual field defects than the CGFS group. Hence, results from hospital-based studies on severity and the rates of progression should be interpreted with caution.


Home abortion - experiences of male involvement.
To gain knowledge about the male partner's experience of being present during an induced home abortion. Twenty-three couples, whose male partner had been present when the woman aborted at home, were interviewed one to two weeks post-abortion. Each of the men supported his partner in her decision to have a home abortion, as this gave him the possibility of being near and of caring for her needs on the expulsion day. All the men were present and all their partners confirmed that they had been supportive. Half the men had been anxious prior to the expulsion, but most considered that their experiences during the expulsion had been 'easier than expected' and their dominant feeling was one of relief. Abortion is an important life event. When taking place at home, it increases the possibility for the couple to share the experience. Sharing an abortion may have a positive impact on those men who lack a sense of responsibility regarding reproductive issues, such as contraceptive use. This could facilitate society's efforts to involve men as a target group in this field. Designing an abortion policy that caters for the needs of both partners is a challenge.


Disposition of Basal Insulin Peglispro Compared with 20-kDa Polyethylene Glycol in Rats Following a Single Intravenous or Subcutaneous Dose.
Basal insulin peglispro (BIL) comprises insulin lispro covalently bound to a 20-kDa polyethylene glycol (PEG) at lysine B28. The biologic fate of BIL and unconjugated PEG were examined in rats given a single 0.5-mg/kg i.v. or 2-mg/kg s.c. dose of BIL with (14)C label in 20-kDa PEG or (125)I label in lispro. Unconjugated (14)C-labeled 20-kDa PEG was dosed at 10 mg/kg i.v. or s.c. Blood, urine, and feces were collected up to 336 hours after dosing. Radioactivity was measured by scintillation spectrometry, and BIL was quantitated by enzyme-linked immunosorbent assay. Area under the curve and half-life for immunoreactive BIL were lower than those for both (14)C and (125)I after subcutaneous and intravenous administration. The half-lives of (14)C after BIL and PEG dosing were similar. The clearance of immunoreactive BIL was 2.4-fold faster than that of (14)C and 1.6-fold faster than (125)I. After a subcutaneous dose of BIL, immunoreactive BIL accounted for 31% of the circulating (125)I and 16% of the circulating (14)C, indicating extensive catabolism of BIL. Subcutaneous bioavailability of BIL was 23%-29%; bioavailability for unconjugated PEG was 78%. For unconjugated PEG, most of the (14)C dose was recovered in urine. For BIL, ≥86% of (125)I was eliminated in urine and (14)C was eliminated about equally in urine and feces. The major (14)C-labeled catabolism product of BIL in urine was 20-kDa PEG with lysine attached. The attachment of 20-kDa PEG to lispro in BIL led to a different elimination pathway for PEG compared with unconjugated 20-kDa PEG.


Bio/chemoinformatics in India: an outlook.
With the advent of significant establishment and development of Internet facilities and computational infrastructure, an overview on bio/chemoinformatics is presented along with its multidisciplinary facts, promises and challenges. The Government of India has paved the way for more profound research in biological field with the use of computational facilities and schemes/projects to collaborate with scientists from different disciplines. Simultaneously, the growth of available biomedical data has provided fresh insight into the nature of redundant and compensatory data. Today, bioinformatics research in India is characterized by a powerful grid computing systems, great variety of biological questions addressed and the close collaborations between scientists and clinicians, with a full spectrum of focuses ranging from database building and methods development to biological discoveries. In fact, this outlook provides a resourceful platform highlighting the funding agencies, institutes and industries working in this direction, which would certainly be of great help to students seeking their career in bioinformatics. Thus, in short, this review highlights the current bio/chemoinformatics trend, educations, status, diverse applicability and demands for further development.


One panel to rule them all: DArTcap genotyping for population structure, historical demography, and kinship analyses, and its application to a threatened shark.
With recent advances in sequencing technology, genomic data are changing how important conservation management decisions are made. Applications such as Close-Kin Mark-Recapture demand large amounts of data to estimate population size and structure, and their full potential can only be realised through ongoing improvements in genotyping strategies. Here we introduce DArTcap, a cost-efficient method that combines DArTseq and sequence capture, and illustrate its use in a high resolution population analysis of Glyphis garricki, a rare, poorly known and threatened euryhaline shark. Clustering analyses and spatial distribution of kin pairs from four different regions across northern Australia and one in Papua New Guinea, representing its entire known range, revealed that each region hosts at least one distinct population. Further structuring is likely within Van Diemen Gulf, the region that included the most rivers sampled, suggesting additional population structuring would be found if other rivers were sampled. Coalescent analyses and spatially explicit modelling suggest that G. garricki experienced a recent range expansion during the opening of the Gulf of Carpentaria following the conclusion of the Last Glacial Maximum. The low migration rates between neighbouring populations of a species that is found only in restricted coastal and riverine habitats show the importance of managing each population separately, including careful monitoring of local and remote anthropogenic activities that may affect their environments. Overall we demonstrated how a carefully chosen SNP panel combined with DArTcap can provide highly accurate kinship inference and also support population structure and historical demography analyses, therefore maximising cost-effectiveness.


Azoreductase from alkaliphilic Bacillus sp. AO1 catalyzes indigo reduction.
Indigo is an insoluble blue dye historically used for dyeing textiles. A traditional approach for indigo dyeing involves microbial reduction of polygonum indigo to solubilize it under alkaline conditions; however, the mechanism by which microorganisms reduce indigo remains poorly understood. Here, we aimed to identify an enzyme that catalyzes indigo reduction; for this purpose, from alkaline liquor that performed microbial reduction of polygonum indigo, we isolated indigo carmine-reducing microorganisms. All isolates were facultative anaerobic and alkali-tolerant Bacillus spp. An isolate termed AO1 was found to be an alkaliphile that preferentially grows at pH 9.0-11.0 and at 30-35 °C. We focused on flavin-dependent azoreductase as a possible enzyme for indigo carmine reduction and identified its gene (azoA) in Bacillus sp. AO1 using homology-based strategies. azoA was monocistronic but clustered with ABC transporter genes. Primary sequence identities were < 50% between the azoA product (AzoA) and previously characterized flavin-dependent azoreductases. AzoA was heterologously produced as a flavoprotein tolerant to alkaline and organic solvents. The enzyme efficiently reduced indigo carmine in an NADH-dependent manner and showed strict specificity for electron acceptors. Notably, AzoA oxidized NADH in the presence, but not the absence, of indigo. The reaction rate was enhanced by adding organic solvents to solubilize indigo. Absorption spectrum analysis showed that indigo absorption decreased during the reaction. These observations suggest that AzoA can reduce indigo in vitro and potentially in Bacillus sp. AO1. This is the first study that identified an indigo reductase, providing a new insight into a traditional approach for indigo dyeing.


Pseudopodial interdigitations between abutted nerve terminals: diffusion traps which occur in several nuclei of the rat limbic system.
Stimulation of the Torpedine ray electric organ can cause the loss of synaptic vesicles and the growth of pseudopodia from the nerve terminals (Boyne, A. F., and S. McLeod (1979) Neuroscience 4: 615-624). The latter embed themselves in corresponding indentations in abutted terminals. The geometry of these pseudopodial indentations (PSIs) can vary: (i) in length, (ii) in the extent of constriction of the base, and (iii) through a compound interaction between different pseudopodia extending in opposite directions. Examination of six rat brain nuclei in the limbic system has shown that their neuropil can be categorized according to the prevalence of either (i) nerve terminals indented by nerve terminal outgrowths (i.e. PSIs) or (ii) nerve terminals indented by dendritic outgrowths: these have been previously termed spinules. Clusters of simple PSIs were seen in the central nucleus of the amygdala, while base-constricted and compound forms were found in the globus pallidus and substantia nigra. Dendritic spinules were prevalent in the nucleus accumbens and the molecular layer of the hippocampus. In the CA4 hilar region of the hippocampus, large nerve terminals containing PSIs were found. The caudate neuropil appeared to be of mixed character in that the small terminals often had spinules but occasionally showed PSIs. Spinules have been recognized for many years and the possibility of their plasticity has been raised previously (Tarrant, S. B, and A. Routtenberg (1977) Tissue Cell 9: 461-473). The present report appears to be first detailed description of an alternative form of invasion which is known to be plastic in the elasmobranch electric organ. It is suggested that the extracellular space between the partners of a PSI could act as variable diffusion traps. If the involved boutons carry action potentials, then nonsynaptic release and accumulation of substances such as potassium, amino acids, and nucleotides may be expected during stimulation. Consequent direct or receptor-mediated effects on the membrane potential could influence transmission through adjacent synapses.


Differential gene expression in Daphnia magna suggests distinct modes of action and bioavailability for ZnO nanoparticles and Zn ions.
Zinc oxide nanoparticles (ZnO NPs) are being rapidly developed for use in consumer products, wastewater treatment, and chemotherapy providing several possible routes for ZnO NP exposure to humans and aquatic organisms. Recent studies have shown that ZnO NPs undergo rapid dissolution to Zn(2+), but the relative contribution of Zn(2+) to ZnO NP bioavailability and toxicity is not clear. We show that a fraction of the ZnO NPs in suspension dissolves, and this fraction cannot account for the toxicity of the ZnO NP suspensions to Daphnia magna. Gene expression profiling of D. magna exposed to ZnO NPs or ZnSO(4) at sublethal concentrations revealed distinct modes of toxicity. There was also little overlap in gene expression between ZnO NPs and SiO(x) NPs, suggesting specificity for the ZnO NP expression profile. ZnO NPs effected expression of genes involved in cytoskeletal transport, cellular respiration, and reproduction. A specific pattern of differential expression of three biomarker genes including a multicystatin, ferritin, and C1q containing gene were confirmed for ZnO NP exposure and provide a suite of biomarkers for identifying environmental exposure to ZnO NPs and differentiating between NP and ionic exposure.


Three mile island. The silent disaster.
From Wednesday, March 28, 1979, to Wednesday, April 4, 1979, Dauphin County, Pennsylvania, was in a state of near-panic in response to the Three Mile Island nuclear accident. The Dauphin County Office of Emergency Preparedness quickly attempted to develop a plan to evacuate not only the population of an area 20 miles in radius from the plant but the short-term and long-term care medical facilities as well. For medical evacuation, a system of classification of patients was defined and matched to needed transportation. Furthermore, a critical coordinating link was established with the Hospital Association of Pennsylvania to identify and categorize relocation beds in receiving hospitals far from the incident site in the event of evacuation. Just as this incident was unusual, so too were the planning activities unique since they were never before conceived or accomplished.


Assessment of the breath alcohol concentration in emergency care patients with different level of consciousness.
Many patients seeking emergency care are under the influence of alcohol, which in many cases implies a differential diagnostic problem. For this reason early objective alcohol screening is of importance not to falsely assign the medical condition to intake of alcohol and thus secure a correct medical assessment. At two emergency departments, demonstrate the feasibility of accurate breath alcohol testing in emergency patients with different levels of cooperation. Assessment of the correlation and ratio between the venous blood alcohol concentration (BAC) and the breath alcohol concentration (BrAC) measured in adult emergency care patients. The BrAC was measured with a breathalyzer prototype based on infrared spectroscopy, which uses the partial pressure of carbon dioxide (pCO₂) in the exhaled air as a quality indicator. Eighty-eight patients enrolled (mean 45 years, 53 men, 35 women) performed 201 breath tests in total. For 51% of the patients intoxication from alcohol or tablets was considered to be the main reason for seeking medical care. Twenty-seven percent of the patients were found to have a BAC of <0.04 mg/g. With use of a common conversion factor of 2100:1 between BAC and BrAC an increased agreement with BAC was found when the level of pCO₂ was used to estimate the end-expiratory BrAC (underestimation of 6%, r = 0.94), as compared to the BrAC measured in the expired breath (underestimation of 26%, r = 0.94). Performance of a forced or a non-forced expiration was not found to have a significant effect (p = 0.09) on the bias between the BAC and the BrAC estimated with use of the level of CO₂. A variation corresponding to a BAC of 0.3 mg/g was found between two sequential breath tests, which is not considered to be of clinical significance. With use of the expired pCO₂ as a quality marker the BrAC can be reliably assessed in emergency care patients regardless of their cooperation, and type and length of the expiration.


Superpolynomial growth in the number of attractors in Kauffman networks.
The Kauffman model describes a particularly simple class of random Boolean networks. Despite the simplicity of the model, it exhibits complex behavior and has been suggested as a model for real world network problems. We introduce a novel approach to analyzing attractors in random Boolean networks, and applying it to Kauffman networks we prove that the average number of attractors grows faster than any power law with system size.


rhIGF-1/rhIGFBP-3 in Preterm Infants: A Phase 2 Randomized Controlled Trial.
To investigate recombinant human insulin-like growth factor 1 complexed with its binding protein (rhIGF-1/rhIGFBP-3) for the prevention of retinopathy of prematurity (ROP) and other complications of prematurity among extremely preterm infants. This phase 2 trial was conducted from September 2014 to March 2016. Infants born at a gestational age of 230/7 weeks to 276/7 weeks were randomly allocated to rhIGF-1/rhIGFBP-3 (250 µg/kg/ 24 hours, continuous intravenous infusion from <24 hours of birth to postmenstrual age 296/7 weeks) or standard neonatal care, with follow-up to a postmenstrual age of 404/7 weeks. Target exposure was ≥70% IGF-1 measurements within 28-109 µg/L and ≥70% intended therapy duration. The primary endpoint was maximum severity of ROP. Secondary endpoints included time to discharge from neonatal care, bronchopulmonary dysplasia, intraventricular hemorrhage, and growth measures. Overall, 61 infants were allocated to rhIGF-1/rhIGFBP-3, 60 to standard care (full analysis set); 24 of 61 treated infants achieved target exposure (evaluable set). rhIGF-1/rhIGFBP-3 did not decrease ROP severity or ROP occurrence. There was, however, a 53% decrease in severe bronchopulmonary dysplasia in the full analysis set (21.3% treated vs 44.9% standard care), and an 89% decrease in the evaluable set (4.8% vs 44.9%; P = .04 and P = .02, respectively) for severity distribution between groups. There was also a nonsignificant trend toward decrease in grades 3-4 intraventricular hemorrhage in the full analysis set (13.1% vs 23.3%) and in the evaluable set (8.3% vs 23.3%). Fatal serious adverse events were reported in 19.7% of treated infants (12/61) and 11.7% of control infants (7/60). No effect was observed on time to discharge from neonatal care/growth measures. rhIGF-1/rhIGFBP-3 did not affect development of ROP, but decreased the occurrence of severe bronchopulmonary dysplasia, with a nonsignificant decrease in grades 3-4 intraventricular hemorrhage. ClinicalTrials.gov: NCT01096784.


Perinatal Bacterial Exposure Contributes to IL-13 Aeroallergen Response.
There is a high prevalence of aeroallergen sensitivity in asthmatic populations, and seroreactivity to aeroallergens early in infancy is associated with increased risk of developing asthma later in life. In addition to allergen sensitivity, asthma development has been associated with differential microbial exposure and infection in early life. We have previously shown that cord blood mononuclear cells respond to common aeroallergens (i.e., house dust mite [Der f1] and cockroach [Bla g2]) as assayed by lymphoproliferation and cytokine (IL-13 and IFN-γ) production. We hypothesized that there is a relationship between perinatal microbial exposure and response to specific aeroallergens. To test this hypothesis, we isolated DNA from cord blood serum samples with known lymphoproliferative and cytokine responses to Bla g2 and Der f1. Bacterial 16S ribosomal DNA amplicon libraries were generated and analyzed using high throughput sequencing of cord blood serum samples. In our analysis, we identified major compositional differences, including diversity and abundance of specific taxa, between groups whose IL-13 response to Der f1 and Bla g2 differed. We demonstrate a strong association between the ratio of Acinetobacter to Proteobacteria and IL-13 production and the probability of IL-13 production after allergen exposure. IL-13 concentrations in serum were also significantly correlated with the diversity of bacterial DNA. Together, these results underscore the relationship between immune responses to allergens and bacterial exposure during perinatal development.


Preparation and characterization of ibuprofen-cetyl alcohol beads by melt solidification technique: effect of variables.
Ibuprofen (IBU) exhibits short half-life, poor compressibility, flowability and caking tendency. IBU melt has sufficiently low viscosity and exhibits interfacial tension sufficient to form droplet even at low temperature. A single step novel melt solidification technique (MST) was developed to produce IBU beads with lower amounts of excipient. Effect of variables was studied using a 3(2) factorial approach with speed of agitation and amount of cetyl alcohol (CA) as variables. The beads were evaluated using DSC, FT-IR and scanning electron microscope (SEM). Yield, micromeritic properties, crushing strength and release kinetics were also studied. Spherical beads with a method yield of above 90% were obtained. The data was analyzed by response surface methodology. The variables showed curvilinear relationship with yield in desired particle size range, crushing strength and, bulk and tap density. The drug release followed non-Fickian case II transport and the release rate decreased linearly with respect to amount of CA in the initial stages followed by curvilinearity at later stages of elution. The effect of changing porosity and tortuosity was well correlated.


Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in children.
To analyze the clinical characteristics and prognosis of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis and to provide a basis for early clinical identification of this disease. The clinical data of 42 cases of anti-NMDAR encephalitis at Department of Pediatrics, Second Xiangya Hospital, Central South University from January 2015 to March 2018 were collected. The clinical features and followed-up outcomes were analyzed retrospectively. There were 15 cases (35.7%) of males and 27 cases (64.3%) of females in 42 children, with a ratio of 1꞉1.8. They were aged from 4 months to 17 years, with an average of (9.20±4.66) years. The most common initial symptoms were seizures (47.6%, 20/42) and mental behavior disorder (35.7%, 15/42). During the course of the disease, 85.7% patients(36/42) had mental and behavior disorder, 85.7% patients (36/42) had epilepsy, 76.2% (32/42) had speech disorder, 66.7% patients (28/42) had dyskinesia, 66.7% patients (28/42) had the decreased level of consciousness, 61.9% patients (26/42) had autonomic instability, and 57.1% (24/42) patients had sleep disorder. All the children had positive antibody against NMDA receptor resistance encephalitis in cerebrospinal fluid. Head MRI showed the abnormal incidence was 50.0% (21/42), and the lesions involved in parietal lobe, frontal lobe, temporal lobe, occipital lobe, midbrain, thalamus, basal ganglia and optic nerve. There was a patient with optic nerve damage combined with myelin oligodendrocyte glycoprotein (MOG) antibody positive. Forty cases were examined by electroencephalogram (EEG), 92.5% cases (37/40) were abnormal, mainly showing diffuse slow waves, and δ brushes could be seen in severe cases. And there was 1 patient (2.4%) complicated with mesenteric teratoma. The mRS score (2.14±1.46) at discharge was significantly lower than the highest mRS score (3.88±1.38) during hospitalization (P<0.05). After 3-39 months of follow-up, mRS score at 3 months after discharge was only 0.81±1.29, which was still improved compared with that at discharge, 76.2% cases (32/42) experienced complete or near-complete recovery (mRS score≤2), and 4.8% (2/42) cases relapsed. There was no mortality; the initial time of immunotherapy and the highest mRS score in the course of the disease were the factors affecting the prognosis. The earlier the starting time for immunotherapy and the lower mRS score in the course of the disease were, the better the prognosis was. Seizures, mental and behavior disorder, dyskinesias, speech disorder and autonomic instability are common clinical manifestations of anti-NMDAR encephalitis in children. The effect of immunotherapy is significant, and the time to start immunotherapy and the severity of the disease are important factors affecting the prognosis. Anti-NMDAR encephalitis can be combined with other autoantibodies, but its clinical significance and mechanism need further study.


Pulmonary modulation of benzo[a]pyrene-induced hemato- and hepatotoxicity in broilers.
Aftermath in several air pollution episodes with high concentrations of polycyclic aromatic hydrocarbons did not significantly affect health and performance of broilers despite its renowned sensitivity to polycyclic aromatic hydrocarbons. The aim of the study was to elucidate the previous lack of response in birds exposed to such severe episodes of air pollution. Benzo[a]pyrene (BaP) was used to simulate the influence of air pollution on hematology, selected organ function, and oxidative stress in broilers. One-day-old chicks were assigned to 5 equal groups composed of a control group, tricaprylin group, and 3 groups treated with BaP (at 1.5 microg, 150 microg, or 15 mg/kg of BW). The BaP was intratracheally administered to 1-d-old chicks for 5 consecutive days. The hematology, liver and kidney function, P450 activity, and malondialdehyde level especially in the group receiving 15 mg of BaP/kg of BW demonstrated evidence of hemato- and hepatoxicity via BaP-induced oxidative stress. The deleterious effect of exposure to high concentration of BaP in broiler chickens was probably due to the anatomy of this species and the half-life of BaP. Although the effect of BaP may be transient or irreversible, pathogen challenges faced during the period of suppression may prove fatal.


Advances in physical rehabilitation of multiple sclerosis.
Multiple sclerosis (MS) is a neurological disorder that heavily affects quality of life (QoL) and demands a multidisciplinary therapeutic approach. This includes multiple protocols and techniques of physical rehabilitation, ranging from conventional exercise paradigms to noninvasive brain stimulation (NIBS). Recently, studies showing the clinical efficacy of physical rehabilitation have remarkably increased, suggesting its disease-modifying potential. Studies in animal models of MS have shown that physical exercise ameliorates the main disease pathological hallmarks, acting as a pro-myelinating and immunomodulatory therapy. NIBS techniques have been successfully applied to treat pain and urinary symptoms and lower limb function and spasticity, especially in combination with physical rehabilitation. Physical rehabilitation is reported to be well tolerated and effective in improving muscle function and fitness even in more disabled patients, and to enhance balance, walking and upper limb functional movements. Moreover, the dual motor--cognitive task performance can be improved by combined training protocols. The literature here reviewed indicates the importance of clinical and preclinical research in addressing the impact of neurorehabilitation on MS disability, highlighting the need of further studies to reach a more comprehensive understanding of the mechanisms involved, the best combination of techniques and the proper timing of application.


The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration.
This study examined the association between the sequence variation/expression of CX3CR1, a chemokine receptor, and age-related macular degeneration (AMD). Peripheral blood from 85 AMD patients and 105 subjects without AMD (controls), as well as ocular tissue from 40 pathological sections with AMD and two normal eye sections, were screened for V249I and T280M, two single nucleotide polymorphisms (SNPs) in CX3CR1. An increased prevalence, with the highest odds ratio of 3.57, of the I249 and M280 carriers was found among the AMD cases as compared with the controls. When comparing CX3CR1 expression in the archived eye sections, CX3CR1 transcripts were not detectable in the maculae of AMD eyes bearing T/M280; however, transcripts were detected in the maculae of normal eyes bearing T/T280 or T/M280 as well as in the AMD maculae bearing T/T280. Furthermore, lower CX3CR1 protein expression was observed in the maculae of AMD eyes bearing T/M280 compared with the controls bearing T/T280. The I249 and M280 alleles result in a lowered number of receptor binding sites and a decreased ligand affinity. Our data suggest that a decrease, caused by sequence variation and/or lower CX3CR1 expression, in CX3CR1-induced cellular activities could contribute to AMD development.


A proteomic and phosphoproteomic analysis of Oryza sativa plasma membrane and vacuolar membrane.
Proteomic and phosphoproteomic analyses of rice shoot and root tonoplast-enriched and plasma membrane-enriched membrane fractions were carried out to look at tissue-specific expression, and to identify putative regulatory sites of membrane transport proteins. Around 90 unique membrane proteins were identified, which included primary and secondary transporters, ion channels and aquaporins. Primary H(+) pumps from the AHA family showed little isoform specificity in their tissue expression pattern, whereas specific isoforms of the Ca(2+) pump ECA/ACA family were expressed in root and shoot tissues. Several ABC transporters were detected, particularly from the MDR and PDR subfamilies, which often showed expression in either roots or shoots. Ammonium transporters were expressed in root, but not shoot, tissue. Large numbers of sugar transporters were expressed, particularly in green tissue. The occurrence of phosphorylation sites in rice transporters such as AMT1;1 and PIP2;6 agrees with those previously described in other species, pointing to conserved regulatory mechanisms. New phosphosites were found in many transporters, including H(+) pumps and H(+):cation antiporters, often at residues that are well conserved across gene families. Comparison of root and shoot tissue showed that phosphorylation of AMT1;1 and several further transporters may be tissue dependent.