Physiological Constants of the Entomopathogenic Bacterium Xenorhabdus nematophila Determined by Microbial Growth Kinetics.
Xenorhabdus nematophila, an entomopathogenic bacterium that symbiotically associates with the entomoparasitic nematode Steinernema carpocapsae, was studied to determine its physiological parameters of glucose utilization. X. nematophila was cultured in chemically defined media containing various concentrations of glucose under optimal conditions utilizing a two-liter fermentation system. Specific growth rates were obtained from each glucose batch. Specific growth rates and their associated glucose concentrations were used to determine physiological parameters. These parameters include the bacterium's substrate utilization constant (K s ) and its maximum specific growth rate (μ max). The bacteria exhibited a K s value of 2.02 mg/L suggesting that X. nematophila has a high affinity for glucose. The μ max of Xenorhabdus was determined to be 1.03 h(-1). Further research is needed to determine if microbial affinities to different substrates have any influence on biological relationships (symbiosis, pathogenicity, parasitism, etc.) between prokaryotes and higher organisms.


Neurodegeneration in the animal model of Menkes' disease involves Bcl-2-linked apoptosis.
Copper plays a key role in brain development, function and survival. Alteration of its homeostasis is suggested to be an aetiological factor in several neurodegenerative diseases. However, the molecular mechanisms relating copper to neurodegeneration are still unknown. In the present report, using morphological analyses of brain sections of mottled/brindled mutant (Mo(br/y)) mice, the animal model of the human genetic copper deficiency associated with neurodegeneration (Menkes' disease), we demonstrated that a high degree of apoptotic cells is present in the neocortex and in the hippocampus. Biochemical characterisation revealed decreased levels of copper content and of the activity of the mitochondrial copper-dependent enzyme cytochrome c oxidase. Copper, zinc-superoxide dismutase activity also shows a slight decrease, while no change was observed for glutathione content. Lower levels of ATP were also found, indicative of a copper-dependent impairment of energy metabolism. Changes appear to be specific for the brain, since no alterations in the activity of liver enzymes were found, although the level of copper was strongly decreased. We also tested biochemical factors involved in cell commitment to apoptosis. The expression of the anti-apoptotic protein Bcl-2, which plays a fundamental role in brain development and morphogenesis, was dramatically decreased and the levels of cytochrome c released from mitochondria into the cytosol were significantly increased. On the basis of these findings, we propose that down-regulation of Bcl-2 can cause neurodegeneration triggered by mitochondrial damage due to copper depletion during brain development in Mo(br/y) mice.


Grommets for otitis media with effusion in children with cleft palate: a systematic review.
No consensus has yet been reached with regard to the link between otitis media with effusion (OME), hearing loss, and language development in children with cleft palate. The objective of this study was to address the effectiveness of ventilation tube insertion (VTI) for OME in children with cleft palate. A dual review process was used to assess eligible studies drawn from PubMed, Medline via Ovid, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, and reference lists between 1948 and November 2013. Potentially relevant papers were selected according to the full text of the articles. Relevant data were extracted onto a data extraction sheet. Nine high- or moderate-quality cohort studies were included in this study. VTI was administered in 38% to 53% of the OME cases, and more severe cases appeared more likely to undergo VTI. Compared with conservative forms of management (eg, watchful waiting), VTI has been shown to be beneficial to the recovery of hearing in children with cleft palate and OME. A growing body of evidence demonstrates the benefits of VTI in the development of speech and language in children with cleft palate and OME. These children face a higher risk of complications than those undergoing conservative treatments, the most common of which are eardrum retraction and tympanosclerosis, with an incidence of ∼ 11% to 37%. This review provides evidence-based information related to the selection of treatment for OME in children with cleft palate. Additional randomized controlled trials are required to obtain bias-resistant evidence capable of reliably guiding treatment decisions. The conclusions in this review are based on underpowered cohort studies and very-low-strength evidence.


USP22 promotes epithelial-mesenchymal transition via the FAK pathway in pancreatic cancer cells.
Epithelial-mesenchymal transition (EMT) contributes to the occurrence and development of tumors, particularly to the promotion of tumor invasion and metastasis. As a newly discovered ubiquitin hydrolase family member, USP22 plays a key role in the malignant transformation of tumors and the regulation of the cell cycle. However, recent studies on USP22 have primarily focused on its role in cell cycle regulation, and the potential mechanism underlying the promotion of tumor invasion and metastasis by abnormal USP22 expression has not been reported. Our studies revealed that the overexpression of USP22 in PANC-1 cells promoted Ezrin redistribution and phosphorylation and cytoskeletal remodeling, upregulated expression of the transcription factors Snail and ZEB1 to promote EMT, and increased cellular invasion and migration. In contrast, blockade of USP22 expression resulted in the opposite effects. In addition, the focal adhesion kinase (FAK) signaling pathway was shown to play a key role in the process of EMT induction in PANC-1 cells by USP22. Thus, the present study suggests that USP22 acts as a regulatory protein for EMT in pancreatic cancer, which may provide a new approach for the targeted therapy of pancreatic cancer.


[Initial experiences with CO2 as a gaseous contrast medium in digital subtraction angiography].
Electronic contrast enhancement allows the use of CO2 as a contrast material for studying the vascular system with DSA. Its use, safety and the information provided were studied in 40 patients and in 5 animal experiments and the results were compared with iodine-containing contrast media. The available results indicate that CO2 is a safe negative contrast medium for peripheral arteriography and that it provides angiograms with a picture quality comparable to those of iodinated contrast media in the extremities. The method can therefore be used to advantage in patients with allergies to the iodinated contrast media and in patients with renal failure.


Mediastinal lymphadenopathy: a variant of incomplete Kawasaki disease.
A 14-month-old girl presented with a 4-d history of fever and generalized exanthema. Four characteristic symptoms of incomplete Kawasaki disease (KD) were present on admission (fever, rash, non-purulent conjunctival injection, oropharyngeal changes) and then followed by oedema of the hands and feet and mild plantar desquamation. The typical laboratory features of KD, such as elevated erythrocyte sedimentation rate, leukocytosis, thrombocytosis, and positive C-reactive protein were also seen. Ultrasound examination of the mediastinum revealed the presence of a lymph node, 30 mm in diameter, below the tracheal carina. Thoracic CT scan confirmed the mediastinal lymph node. The patient was treated with aspirin and intravenous gamma-globulin. Ultrasound study of the mediastinum, which was carried out 6 weeks after hospital discharge, showed that the lymph node had disappeared. This case illustrates that lymph nodes other than cervical lymphadenopathy should be sought when the diagnosis of classical or atypical KD is suspected.


Assessing the phylogeographic history of the montane caddisfly Thremma gallicum using mitochondrial and restriction-site-associated DNA (RAD) markers.
Repeated Quaternary glaciations have significantly shaped the present distribution and diversity of several European species in aquatic and terrestrial habitats. To study the phylogeography of freshwater invertebrates, patterns of intraspecific variation have been examined primarily using mitochondrial DNA markers that may yield results unrepresentative of the true species history. Here, population genetic parameters were inferred for a montane aquatic caddisfly, Thremma gallicum, by sequencing a 658-bp fragment of the mitochondrial CO1 gene, and 12,514 nuclear RAD loci. T. gallicum has a highly disjunct distribution in southern and central Europe, with known populations in the Cantabrian Mountains, Pyrenees, Massif Central, and Black Forest. Both datasets represented rangewide sampling of T. gallicum. For the CO1 dataset, this included 352 specimens from 26 populations, and for the RAD dataset, 17 specimens from eight populations. We tested 20 competing phylogeographic scenarios using approximate Bayesian computation (ABC) and estimated genetic diversity patterns. Support for phylogeographic scenarios and diversity estimates differed between datasets with the RAD data favouring a southern origin of extant populations and indicating the Cantabrian Mountains and Massif Central populations to represent highly diverse populations as compared with the Pyrenees and Black Forest populations. The CO1 data supported a vicariance scenario (north-south) and yielded inconsistent diversity estimates. Permutation tests suggest that a few hundred polymorphic RAD SNPs are necessary for reliable parameter estimates. Our results highlight the potential of RAD and ABC-based hypothesis testing to complement phylogeographic studies on non-model species.


Cements containing syringic acid esters -- o-ethoxybenzoic acid and zinc oxide.
Fissure caries is reduced when syringic acid is incorporated into a cariogenic diet of rats. It was therefore of interest to synthesize n-hexyl and 2-ethylhexyl syringate and to evaluate the properties of cements with these compounds as ingredients. Liquids containing the esters dissolved in o-ethoxybenzoic acid (EBA) - when mixed with powders made up from zinc oxide, aluminum oxide, and hydrogenated rosin - hardened in from four to nine min. Properties of the cements were determined, when possible, according to ANSI/ADA specification tests. Depending on the powder-liquid ratio employed, we obtained compositions with varying physical properties desirable for different dental applications. The syringate cements, compared with the commonly used ZOE materials, have improved compressive and tensile strength, lower water solubility, do not inhibit polymerization, and are compatible with acrylic monomers. These cements pass, and mostly greatly exceed, the requirements for ZOE-type restorative materials. They also bond significantly to resins, composites, and non-precious metals. The bond strength is somewhat less than that of n-hexyl vanillate-EBA cement, but greatly exceeds the adhesion to various substrates of ZOE luting agents. Cements containing n-hexyl syringate were somewhat brittle. Best results were obtained with liquid compositions containing 5% 2-ethylhexyl syringate, 7% n-hexyl vanillate, and 88% EBA, which yielded non-brittle materials. These cements, because of the syringate ingredient, may possess caries-reducing properties. Thus, perhaps in conjunction with fluoride additives, they would be useful as insulating bases, pulp capping agents, root canal sealers, soft tissue packs, or intermediate restoratives.


An analysis of the origins of the cholinergic and noncholinergic septal projections to the hippocampal formation of the rat.
These experiments were directed at determining the proportion and distribution of cholinergic septal cells which project to the rat hippocampal formation. Injections of WGA-HRP were placed into different regions of the hippocampal formation and sections through the septal complex were processed for the simultaneous demonstration of the retrogradely transported marker and for choline acetyltransferase (ChAT) immunoreactivity. Preliminary analysis of adjacent normal series prepared either for the demonstration of ChAT or stained by the Nissl method demonstrated several distinct cell groups in the classically defined medial septal nucleus and vertical limb of the nucleus of the diagonal band. The groups of cells ranged from almost entirely ChAT-positive to entirely noncholinergic. On the basis of shape and size of the constituent cells, the ChAT-positive cells of the septal complex were divided into dorsal, intermediate, and ventral subdivisions. The proportion of retrogradely labeled cells that were also ChAT positive ranged from 22.8% to 77.4% in different experiments. When only the hippocampus and dentate gyrus are considered, this variation can largely be accounted for by the topographic organization of the septohippocampal projection. The medial, noncholinergic half of the medial septal nucleus projects primarily to the rostral or septal portions of the dentate gyrus and hippocampus, whereas the lateral half, in which the dorsal ChAT group is located, projects heavily to more temporal levels. Rostral portions of the hippocampus and dentate gyrus receive most of their cholinergic input from the ventral ChAT cell group which forms a major component of the vertical limb of the nucleus of the diagnoal band. While some ChAT-positive cells in the intermediate group project to the hippocampal formation, they are generally less numerous than those from the dorsal and ventral groups. However, in a control experiment in which the WGA-HRP injection was placed into the cingulate cortex overlying the rostral hippocampal formation, the intermediate ChAT group accounted for 71.2% of the double-labeled cells.


Laparoscopically Limited Anatomic Liver Resections: A Single-Center Analysis for Oncologic Outcomes of the Conceptual Procedure.
Limited anatomic resections (LARs), such as segmentectomies, performed using a fully laparoscopic approach, have gained popularity for liver malignancies. However, the oncologic efficacy of laparoscopic LARs (Lap-LARs) needs further investigation. This cohort study evaluated the oncologic outcomes of Lap-LAR for hepatocellular carcinoma (HCC) and colorectal liver metastasis (CRLM). At a Japanese referral center, 112 patients underwent Lap-LAR using the Glissonean approach and indocyanine green (ICG) fluorescence navigation. Recurrence-free survival (RFS), overall survival (OS), time to interventional failure (TIF), and time to surgical failure (TSF) were assessed. Among the 112 patients (median age, 74 years [range, 66-80 years]; 80 men [71.4 %]), Lap-LAR showed promising results. The median operative time was 348 min (range, 280-460 min), and the median blood loss was 190 mL (range, 95.5-452.0 mL). The median error between the estimated and actual liver volumes was 2 % (1.2-4.8 %). Complications greater than Clavien-Dindo 3a were observed in 11.6 % of the patients. The 5-year RFS, OS, and TIF rates for HCC were 45.1 % ± 7.9 %, 73.1 % ± 6.7 %, and 74.2 % ± 6 .6 %, respectively. The 5-year RFS, OS, and TSF rates for CRLM were 36.8 % ± 8.7 %, 60.1 % ± 13.3 %, and 63.6 % ± 10.4 %, respectively. Lap-LAR showed favorable oncologic outcomes for HCC and CRLM. Its precise technique makes it a promising therapeutic option for liver malignancies. Further comparisons with conventional approaches are warranted.


A rhodopsin gene expressed in photoreceptor cell R7 of the Drosophila eye: homologies with other signal-transducing molecules.
We have isolated an opsin gene from D. melanogaster that is expressed in the ultraviolet-sensitive photoreceptor cell R7 of the Drosophila compound eye. This opsin gene contains no introns and encodes a 383 amino acid polypeptide that is approximately 35% homologous to the blue absorbing ninaE and Rh2 opsins, which are expressed in photoreceptor cells R1-6 and R8, respectively. Amino acid homologies between these different opsins and other signal-transducing molecules suggest an important role for the conserved domains of rhodopsin in the transduction of extracellular signals.


Environmental Exposure to Endocrine Disrupting Chemicals Influences Genomic Imprinting, Growth, and Metabolism.
Genomic imprinting is an epigenetic mechanism that results in monoallelic, parent-of-origin-specific expression of a small number of genes. Imprinted genes play a crucial role in mammalian development as their dysregulation result in an increased risk of human diseases. DNA methylation, which undergoes dynamic changes early in development, is one of the epigenetic marks regulating imprinted gene expression patterns during early development. Thus, environmental insults, including endocrine disrupting chemicals during critical periods of fetal development, can alter DNA methylation patterns, leading to inappropriate developmental gene expression and disease risk. Here, we summarize the current literature on the impacts of in utero exposure to endocrine disrupting chemicals on genomic imprinting and metabolism in humans and rodents. We evaluate how early-life environmental exposures are a potential risk factor for adult metabolic diseases. We also introduce our mouse model of phthalate exposure. Finally, we describe the potential of genomic imprinting to serve as an environmental sensor during early development and as a novel biomarker for postnatal health outcomes.


Burkholderia cepacia sepsis among neonates.
Burkholderia cepacia is a rare cause of sepsis in newborns and its transmission involves human contact with heavily contaminated medical devices and disinfectants. The authors aimed to determine epidemiology, clinical features, antibiotic sensitivity pattern, complications and outcome of blood culture proven B. cepacia infections in 12 neonates. All neonates were outborn, 5 preterm and 7 term. B. cepacia was isolated from blood in all and concurrently from CSF in three neonates. Lethargy and respiratory distress (41.7 %) were major presenting features. Five newborns (41.7 %) required mechanical ventilation for 3-7 d. Highest bacterial susceptibility was observed for meropenem (100 %), followed by cefoperazone-sulbactam, piperacillin-tazobactam, sulfamethoxazole-trimethoprim (all 83 %), ceftazidime (75 %) and ciprofloxacin (42 %). Piperacillin-tazobactam, ciprofloxacin and cotrimoxazole either singly or in combination led to complete recovery of 11 (91.7 %) newborns; one developed hydrocephalus. Eight of nine infants who completed 6 mo follow up were normal. Prompt recognition and appropriate antibiotic therapy for B. cepacia infection results in complete recovery in majority.


Fingertip Fiber Optical Tactile Array with Two-Level Spring Structure.
Tactile perception is a feature benefiting reliable grasping and manipulation. This paper presents the design of an integrated fingertip force sensor employing an optical fiber based approach where applied forces modulate light intensity. The proposed sensor system is developed to support grasping of a broad range of objects, including those that are hard as well those that are soft. The sensor system is comprised of four sensing elements forming a tactile array integrated with the tip of a finger. We investigate the design configuration of a separate force sensing element with the aim to improve its measurement range. The force measurement of a single tactile element is based on a two-level displacement that is achieved thanks to a hybrid sensing structure made up of a stiff linear and flexible ortho-planar spring. An important outcome of this paper is a miniature tactile fingertip sensor that is capable of perceiving light contact, typically occurring during the initial stages of a grasp, as well as measuring higher forces, commonly present during tight grasps.


Positional nystagmus in patients with chronic dizziness.
In elderly people, chronic dizziness is endemic. However, chronic dizziness of unknown origin is difficult to assess. To investigate whether mild unrecognised benign paroxysmal positional vertigo (BPPV) is a cause of isolated chronic dizziness in the elderly. The prevalence of extremely weak, horizontal, direction changing apogeotropic positional nystagmus (HAPN) that had not been detected by conventional examination was evaluated in 200 patients with isolated chronic dizziness and in 155 age matched control subjects without dizziness. A high prevalence of weak HAPN was found in patients with isolated chronic dizziness (98/200 (49.0%)) compared with the prevalence in control subjects without dizziness (25/155 (16.1%); p<0.0001). Symptoms improved in some patients by daily positional exercise for BPPV. Because BPPV is the most common cause of dizziness in the elderly, and HAPN is a characteristic of horizontal canal BPPV, our findings suggest that mild persistent BPPV is a possible cause of chronic dizziness of otherwise unknown origin in the elderly.


Scribble regulates an EMT polarity pathway through modulation of MAPK-ERK signaling to mediate junction formation.
The crucial role the Crumbs and Par polarity complexes play in tight junction integrity has long been established, however very few studies have investigated the role of the Scribble polarity module. Here, we use MCF10A cells, which fail to form tight junctions and express very little endogenous Crumbs3, to show that inducing expression of the polarity protein Scribble is sufficient to promote tight junction formation. We show this occurs through an epithelial-to-mesenchymal (EMT) pathway that involves Scribble suppressing ERK phosphorylation, leading to downregulation of the EMT inducer ZEB. Inhibition of ZEB relieves the repression on Crumbs3, resulting in increased expression of this crucial tight junction regulator. The combined effect of this Scribble-mediated pathway is the upregulation of a number of junctional proteins and the formation of functional tight junctions. These data suggests a novel role for Scribble in positively regulating tight junction assembly through transcriptional regulation of an EMT signaling program.


[Effect of wheat bran fiber on vitamin status of weaning rats with alimentary polyhypovitaminosis].
Effect of wheat bran on the vitamin status of rats adequately provided with vitamins or insufficiently supplied with vitamins has been investigated. 32 male Wistar weaning rats (initial body mass--49-67g) were randomly divided into 4 groups and fed with complete semi-synthetic diet, containing 100 or 20% of vitamin mixture with or without addition of wheat bran (5% of diet mass) for 35 days. The animals of the control group received 100% of vitamin mixture without adding of wheat bran; 2 group--received those diet with wheat bran; 3 deficient group--20% of vitamin mixture with full exclusion of vitamins E, B1 and B2; 4 group--20% of vitamin mixture and wheat bran. The inclusion of wheat bran in full semi-synthetic diet has been accompanied by significant decrease of alpha-tocopherol liver content on 17% (p = 0.006), significant increase of vitamin B1 liver level on the 16% (p = 0.027) and blood plasma vitamin D elevation on 19% (p = 0.017), as well as a tendency (p = 0.059) to increase the liver level of vitamin B2. Indicators of vitamin A status as well as plasma vitamin E concentration, liver and blood plasma MDA levels were not changed in this group rats. The 5-fold reduction of the vitamin mixture quota and the exclusion of vitamins E, B1 and B2 resulted in a significant (p < 0.05) 1.6-1.8 fold decreased in animal body weight and liver mass and the manifestation of the deep external signs of vitamin deficiency. Young animals were more sensitive than adult animals to a lack of vitamins in the diet. Vitamin A (retinol palmitate) liver content in rats from this group was 25.1-fold reduced, vitamin E (alpha-tocopherol)--2.1-fold, vitamins B1 and B2--by 57 and 38% compared with animals received a complete control diet (p < 0.05). Blood plasma concentration of vitamins A, E, D was 19-34% decreased. Adding of bran in vitamin deficit diet led to increased consumption of vitamin B--on 40%, vitamins B2 and E--21%, both due to their natural content in the bran, and as a result of increased eatability of the feed by 16% relative to deficient group due to improved taste of the diet. Enrichment of vitamin scarce diet with wheat bran led to an increase in body weight by 56%, the efficiency of the diet by 67%. This circumstance didn't allow to reveal the effect of dietary fiber on the vitamin status of rats with polyhypovitaminosis. The significant (p < 0.05) increase of retinol plasma level by 34% and liver and blood plasma tocopherol content by 17% and 22% and reduction of MDA blood plasma level by 24% took place in animals from this group compared to a group of rats receiving vitamin deficit diet without any effect on liver MDA level, liver vitamin A, B1 and B2 content and heart coenzyme Q10 level. The results obtained suggest that wheat bran inclusion in the diet of rats adequately supplied with vitamins may lead to a deficiency of vitamin E.


Characterisation of human soft palate muscles with respect to fibre types, myosins and capillary supply.
Four human soft palate muscles, and palatopharyngeus, the uvula, the levator and tensor veli palatini were examined using enzyme-histochemical, immunohistochemical and biochemical methods and compared with human limb and facial muscles. Our results showed that each palate muscle had a distinct morphological identity and that they generally shared more similarities with facial than limb muscles. The palatopharyngeus and uvula muscles contained 2 of the highest proportions of type II fibres ever reported for human muscles. In contrast, the levator and tensor veli palatini muscles contained predominantly type I fibres. A fetal myosin heavy chain isoform (MyHC), not usually found in normal adult limb muscles, was present in a small number of fibres in all palate muscles. The mean muscle fibre diameter was smaller than in limb muscles and the individual and intramuscular variability in diameter and shape was considerable. All palate muscles had a high capillary density and an unusually high mitochondrial enzyme activity in the type II fibres, in comparison with limb muscles. No ordinary muscle spindles were observed. The fibre type and MyHC composition indicate that the palatopharyngeus and uvula muscles are functionally involved in quick movements whereas the levator and tensor veli palatini muscles perform slower and more continuous contractions. The high aerobic capacity and the rich capillarisation suggest that the palate muscles are relatively fatigue resistant. Absence of ordinary muscle spindles indicates a special proprioceptive control system. The special morphology of the palate muscles may be partly related to the unique anatomy with only one skeletal insertion, a feature consistent with muscle work at low load and tension and which may influence the cytoarchitecture of these muscles. Other important factors determining the special morphological characteristics might be specific functional requirements, distinct embryological origin and phylogenetic factors.


Nitric oxide in human skin: current status and future prospects.
The gaseous free radical nitric oxide is an important biologic mediator with physiologic and pathophysiologic roles in nearly every organ system. Because of its unique biologic activity, unusual chemical structure, and unprecedented mechanisms of action, nitric oxide, arguably more than any other natural product, has opened new avenues to investigate cellular processes. Nitric oxide is generated in biologic tissues by specific nitric oxide synthases that metabolize arginine and molecular oxygen to citrulline and nitric oxide. Besides its function as a diffusible messenger in the vasculature and in neurons, nitric oxide also plays a key role in innate immunity and inflammation. Recent progress has allowed the identification of the nitric oxide pathway in several cell types that reside in the skin, including keratinocytes, melanocytes, Langerhans cells, fibroblasts, and endothelial cells. Convincing evidence suggests that nitric oxide synthesis in these cells can be modulated by calcium-mobilizing agonists as well as diverse inflammatory and immune stimuli, and thereby contributes to the pathogenesis of several human skin diseases. Characterization of these intrinsic and extrinsic regulatory stimuli of nitric oxide synthesis has afforded substantial insights into the role of nitric oxide in inflammatory, hyperproliferative, and autoimmune skin diseases, as well as skin cancer, and may ultimately form the basis for future therapeutic intervention. The demonstrable and potential roles of nitric oxide in skin disease pathogenesis and treatment are the subjects of this review.


Lidocaine patch for acute pain management: a meta-analysis of prospective controlled trials.
Local anesthetic is one of the cornerstones of multimodal analgesia. We investigated the efficacy of the lidocaine patch for acute pain management. We searched MEDLINE, CINAHL, Scopus, and the Cochrane Controlled Trials Register for published prospective controlled clinical trials that evaluated the analgesic effect of the lidocaine patch for acute or postoperative pain management (1966--2014). The outcomes were postoperative opioid consumption, pain intensity and length of hospital stay. Five trials comparing the lidocaine patch with control (no treatment/placebo) for acute or postoperative pain treatment/management were included in this meta-analysis. Data was analyzed on 251 patients. Between the lidocaine patch group and the control group, no significant difference was found for all three outcomes (all p > 0.05). For postoperative opioid consumption, mean difference (MD) was -8.2 mg morphine equivalent (95% CI -28.68, 12.24). For postoperative pain intensity, MD was -9.1 mm visual analog scale or equivalent (95% CI -23.31, 5.20). For length of hospital stay, MD was -0.2 days (95% CI -0.80, 0.43). Application of a lidocaine patch may not be an effective adjunct for acute and postoperative pain management, in terms of pain intensity, opioid consumption and length of hospital stay. The limitations were a small number of included studies, potential biases from some unblinded studies, clinical heterogeneity between studies, and incomplete reported data for adjunct analgesics.


Phosphorylation regulates Id3 function in vascular smooth muscle cells.
Understanding the mechanisms that regulate cell cycle progression in vascular smooth muscle cells (VSMCs) is key to understanding and modulating vascular lesion formation. Results of the present study provide the first evidence that phosphorylation of the helix-loop-helix factor Id3 in VSMCs occurs in vitro and in vivo and provides a regulatory switch controlling Id3-induced regulation of p21Cip1 and VSMC growth.


Adaptive control of modal properties of optical beams using photothermal effects.
We present an experimental demonstration of adaptive control of modal properties of optical beams. The control is achieved via heat-induced photothermal actuation of transmissive optical elements. We apply the heat using four electrical heaters in thermal contact with the element. The system is capable of controlling both symmetrical and astigmatic aberrations providing a powerful means for in situ correction and control of thermal aberrations in high power laser systems. We demonstrate a tunable lens with a focusing power varying from minus infinity to -10 m along two axes using SF57 optical glass. Applications of the proposed system include laser material processing, thermal compensation of high laser power radiation, and optical beam steering.


Localised invasive sino-orbital aspergillosis: characteristic features.
To describe the characteristic constellation of historical, clinical, radiographic, and histopathological findings of localised invasive sino-orbital aspergillosis based on the authors' recent experience of four consecutive cases presenting over a 6 month period. Treatment and outcome are reviewed. A case series of four patients with review of the English language literature. There have been 17 reported cases of invasive sino-orbital aspergillosis in healthy individuals over the past 33 years. The authors report four patients who presented during a 6 month period with persistent and significant pain followed by progressive ophthalmic signs-clinical histories reflecting the literature. Similar imaging findings were also noted: focal hypodense areas within apical infiltrates on contrasted computed tomography correspond to abscesses seen at surgery, and sinus obliteration or involvement of the adjacent sinus lining was noted on magnetic resonance imaging. Bone erosion (often focal) was also seen. There is frequently a delay in making the correct diagnosis, and often disease progression occurs despite treatment. The authors encountered four cases of invasive sino-orbital aspergillosis, three of which occurred in otherwise healthy individuals. The clinician must be aware of the characteristic presentation so that earlier diagnosis, management, and improved outcomes can be achieved.


Clinical validation of 40-mmHg carotid stump pressure for patients undergoing carotid endarterectomy under general anesthesia.
The aim of this study was to validate a mean stump pressure (SP) of 40 mmHg as the cut off threshold for shunting during carotid endarterectomy (CEA). A prospective analysis of recently symptomatic carotid stenosis patients undergoing fast-track CEA under general anesthesia. An arbitrary cut-off threshold of 40 mmHg (mean) was defined as the indication for shunt insertion. With an SP<40 mmHg systemic blood pressure was increased 10-20% using sympathomimetic drugs. Patients with an SP≥40 mmHg CEA were operated without a shunt. A neurological observation scheme was filled out preoperatively by the anesthesiologist and postoperatively during the first 24 hours after surgery. Endpoints for validation of SP were per new transient ischemic attack (TIA) or stroke (ipsilateral or contralateral), hypoperfusion/hypoxia syndrome or death before discharge from hospital. One hundred and twenty consecutive CEAs were performed in recently symptomatic patients. A significant correlation between SP and the contralateral stenosis degree of internal carotid artery (ICA) was found in our study P=0.05. Sixteen patients (14%) had SP<40 mmHg after clamping the carotid arteries. Raising blood pressure intra-operatively by 10-20% reduced the incidence of shunt insertion to only three patients (80% reduction). Of the 120 CEAs, only 2.5% (95% CI 1-6%) of patients required shunt. There was no post-operative TIA or stroke in our study. Two patients (1.65%) suffered early TIA from ipsilateral ICA after discharge from the vascular unit. Using a mean SP of 40 mmHg as a threshold seems to be a safe, easy and cheap method for selective shunt insertion in fast track CEA under general anesthesia with a zero false-negative rate. Raising the systemic blood pressure by 10-20% during cross clamping increased SP above the threshold value 40 mmHg, thus avoiding shunt insertion in a number of patients.


Trait-based classification and environmental drivers of phytoplankton functional structure from anthropogenically altered tropical creek, Thane Creek India.
The present study on variability in phytoplankton functional structure through a trait-based approach described the species-trait-environmental relationship and its possible impact on ecosystem functioning. Based on trait similarities 102 phytoplankton species were clubbed into 14 distinct functional groups. Among others, FGs-XI and XII (small size, chain-forming species with medium to high SA:V ratio and space between cells in chain) were the most dominant due to their competitive advantage in resource utilization and avoidance of loss processes. The morphological traits space between cells and cellular protrusion along with temperature and ammonia played a decisive role in their seasonal succession. Eutrophication in Thane Creek favors the dominance of anti-grazing traits which increases the phytoplankton biomass through efficient resource acquisition but can encumber the energy transfer efficiency. The dominance of HAB species impedes ecosystem functioning which raises public health concerns. The strong correlation of environmental variables with phytoplankton functional structure reinforces the practical implementation of a trait-based approach for understanding phytoplankton community dynamics under varying environmental conditions.


Tumor necrosis factor-independent protective effect of recombinant IFN-gamma against acute toxoplasmosis in T cell-deficient mice.
rIFN-gamma conferred remarkable resistance against acute infection with Toxoplasma gondii in T cell-deficient (athymic nude) mice. Mice that received an i.p. injection of rIFN-gamma every other day beginning 24 h before infection for a total of eight doses survived significantly longer than untreated control mice although all of the treated mice died after the lymphokine was discontinued. Mice that received 14 doses of rIFN-gamma survived significantly longer than those that received eight doses of the lymphokine although mice started dying soon after the final (14th) injection of rIFN-gamma and eventually all of the treated mice died. Histologic study revealed that the IFN-gamma treatment prevented proliferation of the organisms in all organs examined, including brain, lung, heart, liver, and spleen. The treatment was effective even when started 1 day after infection. Peritoneal macrophages obtained from mice injected with rIFN-gamma were activated and effectively killed tachyzoites of T. gondii in vitro. TNF activity could not be detected in sera of the infected mice during treatment with rIFN-gamma. Administration of anti-TNF antibody did not affect the protective effect of rIFN-gamma against T. gondii infection. These facts indicate that rIFN-gamma can confer resistance to acute infection with T. gondii without collaboration of lymphokines derived from T cells and TNF. This suggests that rIFN-gamma may be effective for therapy of toxoplasmosis in immunosuppressed patients who have impaired activity of T cell function, especially those with AIDS.


Patients' and rheumatologists' perspectives on the efficacy and safety of low-dose glucocorticoids in rheumatoid arthritis-an international survey within the GLORIA study.
To evaluate the current perspectives of patients and health professionals regarding the efficacy and safety of low-dose glucocorticoids (GCs) in RA. Two online surveys were disseminated to patients and health professionals, in their native language, through national patient organizations and national rheumatology medical societies, respectively. SurveyMonkey®, MediGuard.org and the Glucocorticoid Low-dose Outcome in RA Study (GLORIA) website were used to offer and deliver these surveys. A total of 1221 RA patients with exposure to GCs, and 414 rheumatologists completed the surveys. Patients and rheumatologists reported high levels of agreement regarding the efficacy of low-dose GCs: at least 70% considered that they are very rapid and effective in the control of signs and symptoms of RA. However, half of the patients also reported having suffered serious adverse events with GCs, and 83% described concerns about safety. The majority of rheumatologists estimated that endocrine, ophthalmologic and cutaneous adverse events affect >4% of all patients treated with low-dose GCs for 2 years, based on a heat map. RA patients with self-reported exposure to GCs express high levels of satisfaction with low-dose GCs efficacy, as do rheumatologists. However, both expressed excessive concerns regarding the safety of GCs (greatly exceeding the published evidence data), which may compromise the optimal use of this medication. This study indicates that there is an unmet need for appropriately designed prospective trials that shed light on the real risk associated with low-dose GCs, as well as a need for renovated educational programs on the real benefits and harms of low-dose GCs, for both patients and physicians.


[Mechanisms of disorders of the bioenergetic functions of mitochondrial membranes in hypoxia].
Evidence is provided that the following events take place in the cell in hypoxia and reoxygenation: expenditure of residual oxygen; a fall in the level of macroergic compounds; entry of calcium ions into the hyaloplasm both from the outside and from the mitochondria; activation of mitochondrial A2 phospholipase (possibly along with the other phospholipases); increase of membrane ion permeability (first phase of separation). This stage corresponds to the "irreversibility point" in cell damage because if the supply of oxygen to the cell is restored after it, the cell will not "recover" but, instead, will be damaged still more. This occurs as the result of active swelling of the mitochondria, inhibition of respiration and bioenergetic functions (the second stage of separation and loss of Ca-accumulating property by the mitochondria), irreparable damage to the cell with autolysis.


Altered electrical activity in colonic smooth muscle cells from dystrophic (mdx) mice.
Because the colon from dystrophic (mdx) mice shows an altered motor pattern, probably due to neural disorders, our aim was to examine the electrophysiological properties of muscle cells and the functionality of nitrergic transmission in circular muscle from normal and mdx colon. Normal colonic cells (resting membrane potential [RMP] about -50 mV) showed spontaneous hyperpolarizations (inhibitory junction potentials; IJPs) and cyclic slow depolarizations were sometimes recorded. Mdx colon had a depolarized RMP (about -36 mV) and spontaneous IJPs, but the cyclic activity was never observed. In the normal colon, Nomega-nitro-L-arginine methyl ester (L-NAME) induced depolarization and abolished the cyclic activity. In the mdx colon, L-NAME caused a slight depolarization. Both preparations displayed the same value of RMP in the presence of L-NAME. In normals, neural stimulation induced nonadrenergic, noncholinergic IJPs composed of fast hyperpolarizations followed by a nitrergic slow hyperpolarization, selectively abolished by L-NAME. In the mdx colon the evoked IJPs were composed only of the initial fast hyperpolarization, the nitrergic component being absent. The hyperpolarization to sodium nitroprusside was not significantly different in both preparations. We conclude that the colon from animals lacking in dystrophin displays different electrophysiological features because of an impairment of nitric oxide function.


Symmetry of deterministic ratchets.
We consider the overdamped motion of a Brownian particle in an unbiased force field described by a periodic function of coordinate and time. A compact analytical representation has been obtained for the average particle velocity as a series in the inverse friction coefficient, from which follows a simple and clear proof of hidden symmetries of ratchets, reflecting the symmetry of summation indices of the applied force harmonics relative to their numbering from left to right and from right to left. We revealed the conditions under which (i) the ratchet effect is absent; (ii) the ratchet average velocity is an even or odd functional of the applied force, whose dependences on spatial and temporal variables are characterized by periodic functions of the main types of symmetries: shift, symmetric, and antisymmetric, and universal, which combines all three types. These conditions have been specified for forces with those dependences of a multiplicative (or additive-multiplicative) and additive structure describing two main ratchet types, pulsating and forced ratchets. We found the fundamental difference in dependences of the average velocity of pulsating and forced ratchets on parameters of spatial and temporal asymmetry of potential energy of a particle for systems in which the spatial and temporal dependence is described by a sawtooth potential and a deterministic dichotomous process, respectively. In particular, it is shown that a pulsating ratchet with a multiplicative structure of its potential energy cannot move directionally if the energy is of the universal symmetry type in time; this restriction is removed in the inertial regime, but only if the coordinate dependence of the energy does not belong to either symmetric or antisymmetric functions.


Fine mapping and characterization of the L-polymerase-binding domain of the respiratory syncytial virus phosphoprotein.
The minimum requirement for an active RNA-dependent RNA polymerase of respiratory syncytial virus (RSV) is a complex made of two viral proteins, the polymerase large protein (L) and the phosphoprotein (P). Here we have investigated the domain on P that is responsible for this critical P-L interaction. By use of recombinant proteins and serial deletions, an L binding site was mapped in the C-terminal region of P, just upstream of the N-RNA binding site. The role of this molecular recognition element of about 30 amino acid residues in the L-P interaction and RNA polymerase activity was evaluated in cellula using an RSV minigenome system and site-directed mutagenesis. The results highlighted the critical role of hydrophobic residues located in this region. Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants. Since no vaccine and no good antivirals against RSV are available, it is essential to better understand how the viral machinery functions in order to develop new antiviral strategies. Like all negative-strand RNA viruses, RSV codes for its own machinery to replicate and transcribe its genome. The core of this machinery is composed of two proteins, the phosphoprotein (P) and the large protein (L). Here, using recombinant proteins, we have mapped and characterized the P domain responsible for this L-P interaction and the formation of an active L-P complex. These findings extend our understanding of the mechanism of action of RSV RNA polymerase and allow us to define a new target for the development of drugs against RSV.


Performance of a new implant system and drilling protocol-A minipig intraoral dental implant model study.
A new implant system encompassing implants with a tri-oval cross-sectional design and a simplified site preparation protocol at low speed and no irrigation has been developed. The objective of this study was to assess the safety and efficacy of the new implant system using the minipig intraoral dental implant model. Eight Yucatan minipigs were included. Twelve weeks after extractions, four implants per animal were randomly placed and allowed to heal transmucosal for 13 weeks: two Ø3.5 × 10 mm implants with a back-tapered collar and circular cross-section (control) and two Ø3.5 × 11 mm implants with tri-oval collar and cross-section (test). MicroCT and histological analysis was performed. Thirty-two implants were placed; one implant for the control group was lost. Histologically, BIC was higher in the test compared with the control group (74.1% vs. 60.9%, p < .001). At the platform level, inflammation was statistically significantly higher albeit mild in the test compared with the control group. No other significant differences were observed between groups. MicroCT analysis showed that bone-to-implant-contact (BIC) and trabecular thickness were statistically significantly higher for the test than the control group. Test group had significantly higher first BIC distance than controls on lingual sites. The present study results support the safety and efficacy of the new dental implant system and simplified site preparation protocol; human studies should be carried out to confirm these findings.


Influence of heat treatment on structural, mechanical and wear properties of crosslinked UHMWPE.
New crosslinked ultra high molecular weight polyethylenes (UHMWPEs) have recently been developed, characterized and introduced in clinical applications. UHMWPE cross-linking treatments are very promising for reducing osteolysis induced by wear debris. The irradiation type, gamma or beta, the dosage and the thermal treatment performed during or following the irradiation process are all factors affecting polyethylene wear resistance. Thermal stabilization treatments performed after or during the irradiation process at a temperature above melting point (i.e. >130 degrees C) have been proven to effectively remove the free radicals generated during irradiation from UHMWPE, but their effect on the mechanical properties of UHMWPE are not completely clear. In addition to wear rate reduction, maintaining good mechanical properties is fundamental aspect in designing the new generation of crosslinked UHMWPE for artificial load bearing materials, especially considering the application in total knee replacements. In this study, we investigated the influence of different stabilization treatments, performed after gamma irradiation, on structural, wear and mechanical properties of UHMWPE. We performed four different stabilization treatments, with different temperatures and cooling rates, on 100 kGy gamma irradiated UHMWPE. Structural properties of UHMWPE were assessed by differential scanning calorimetry (DSC). To assess the mechanical performance of the materials, uni-axial tensile tests were performed according to the ASTM D638 standard, bi-axial tension performance was evaluated by small punch tests (ASTM F2183-02), toughness resistance was evaluated by the Izod method (ASTM F648), and cold flow resistance was analysed by a dynamic compressive test. Evaluation of wear resistance was by a multidirectional pin-on-disk screening machine. Materials considered were in ""aged"" and ""non-aged"" conditions. Results confirmed that cross-linking greatly enhances UHMWPE wear resistance, but introduces some detrimental effects on the mechanical properties. In this study, we found that the negative ef-fects on the mechanical properties of crosslinked UHMWPE can be modulated, to some extent, by choosing a thermal stabiliza-tion treatment at a correct temperature and cooling rate. (Journal of Applied Biomaterials & Biomechanics 2004; 2: 20-8).


Factors associated with stunting in infants aged 5-11 months in the Dodota-Sire District, rural Ethiopia.
The contribution of various factors to malnutrition, particularly stunting, may differ among areas and communities. This cross-sectional study aimed to estimate the level of malnutrition and identify factors associated with the high level of stunting in breast-fed infants aged 5-11 mo living in Dodota-Sire District, Ethiopia. Infants (n = 305) and their mothers were examined physically, and anthropometric and demographic data were collected. The content of zinc, calcium and copper in breast milk was measured, and data collected on the type, frequency of consumption, and time of introduction of supplementary feeding. Overall, 36% were stunted, 41% underweight and 13% wasted. The highest prevalence of malnutrition was seen in infants aged 9-11 mo. Among mothers, 27% had chronic energy deficiency (body mass index, <18.5 kg/m(2)) and 20% were night blind, indicating that vitamin A deficiency was a serious problem. Infants fed >3 times/d, consuming >600 mL/d or consuming cow's milk in addition to cereals and/or legumes had markedly higher length-for-age Z-scores than their peers fed less frequently, consuming less food or not consuming cow's milk [differences: 0.39, 95% confidence interval (CI): 0.04-0.74; 0.17, 95% CI: 0.02-0.32; 0.40, 95% CI: 0.07-0.72, respectively). Infants of mothers with low concentrations of zinc in their breast milk were more stunted. In conclusion, the quality and quantity of foods consumed by infants is insufficient to prevent stunting. Thus it is necessary to increase the nutrient supply to infants by increasing intake and nutrient concentration of breast milk and of supplementary foods they consume, and by providing supplements to infants where appropriate.


Overlay of conventional angiographic and en-face OCT images enhances their interpretation.
Combining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans. In various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image. The confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone. Combining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology.


Long-wavelength visible to near infrared photoluminescence from carbon-bridged styrylstilbene and thiadiazole conjugates in organic and aqueous media.
Donor-acceptor-donor conjugates composed of electron-donating carbon-bridged styrylstilbene (COPV2) and electron-accepting thiadiazole derivatives equipped with carbazolyl (Cz) terminators, Cz-COPV2-A-COPV2-Cz (A = benzothiadiazole (BTz), naphthobis(thiadiazole) (NTz), or benzobis(thiadiazole) (BBTz)), were newly synthesized and found to serve as efficient and stable long-wavelength photoluminescent dyes in organic and aqueous media. In particular, Cz-COPV2-BBTz-COPV2-Cz showed photoluminescence in the near infrared region (895-927 nm) with a photoluminescence quantum yield (PLQY) of up to 0.19 in cyclohexane and of 0.02-0.03 in THF/water mixtures. Its analogues with weaker acceptors, Cz-COPV2-BTz-COPV2-Cz and Cz-COPV2-NTz-COPV2-Cz, showed yellow to deep-red emission in organic solvents, with PLQYs of up to 0.71 in organic solvents and 0.45 in THF/water mixtures.


Fruit and vegetable intake and bone health in women aged 45 years and over: a systematic review.
High fruit and vegetable intake may be associated with improved bone status among women aged ≥ 45 years. This is the first systematic review that specifically assessed this association and identified research gaps. The benefits of fruit and vegetables (F&V) on bone health remain unclear. Further studies are needed. F&V have several components that are beneficial to bones. Some studies report that high F&V intake is associated with improved bone status in middle aged and aged women; however, findings are inconsistent. The objective was to systematically review observational and interventional studies that investigated the effects of F&V intake on incidence of osteoporotic fractures, bone mineral density (BMD), and bone turnover markers (BTM) in women aged ≥ 45 years and to identify potential research gaps. Electronic databases were searched, and peer-reviewed manuscripts published in English, with F&V intake as a main dietary exposure, were included. Data selection, extraction, and evaluation of risk of bias were performed independently by two reviewers. Eight studies were included. One cohort study reported cross-sectional as well as longitudinal data. There was significant between-study heterogeneity in design, definition, and amount of F&V intake, outcomes, analyses, and reporting of results. Two studies had low, two had moderate, and four had high risk of bias. Among reports with low or moderate risk of bias, two cross-sectional analyses reported positive associations between F&V intake and BMD of the forearm, lumbar spine, or total hip, whereas one randomized controlled trial and two prospective cohort analyses reported no effects. One trial reported no associations between F&V and BTM. Based on limited evidence, the benefits of F&V on bone health remain unclear for women aged ≥ 45 years. Further studies with low risk of bias are needed.


[Use of catalytic properties of iron-containing salts in immunoanalysis].
The possibility of using inorganic catalysts as markers for solid-phase immunoassay on the plates is shown with iron-containing hydrosols: ferrum hydroxide, ammonium ferriglycerate, and ferrum hydroxide modified with potassium ferrocyanide. Diagnostic agents based on iron-containing sols with dispersion of 0.5 to 0.8 mm bound to immunoglobulins or staphylococcal protein A are no less sensitive than the immunoperoxidase agents, provided the same developing system is used (o-phenylenediamine + hydrogen peroxide). The sensitivity of solid-phase immunocatalytical assay of purified vaccinia and Venezuelan equine encephalomyelitis virus antigens was about 2 and 10 ng/ml, respectively. Hence, inorganic catalysts are prospective markers for immunoassay.


A new application of imprinted polymers: speciation of organotin compounds.
Molecular imprinting technology has been employed for the first time to prepare a specifically affinity chromatographic stationary phase for speciation purposes. Tributyltin has been chosen as the template molecule and the non-covalent approach has been applied. Three different polymerization methods have been evaluated: (i) a composite material, (ii) a polymer prepared via-Iniferter grafting; (iii) an emulsion polymer. Columns packed with different polymers have been evaluated by liquid chromatography (LC) coupled to inductively coupled plasma mass spectrometry (ICP-MS). The chromatographic conditions as well as the analytical characteristics of the developed method are discussed in this paper. Our findings have shown formation of specific cavities in the grafted Iniferter as well as in the emulsion polymers with the latter achieving resolution of four organotin compounds. Detection limits are similar to those obtained with commercial, but not specific, stationary phases (6 pg for monobutyltin, MBT; 10 pg for both tributyltin, TBT, and triphenyltin, TPhT; and 20 pg for dibutyltin, DBT). The main advantage of this proposed stationary phase is that good recovery is obtained for all species, including MBT. Baseline resolution for TBT and TPhT has also been obtained. The high selectivity of this column prevents matrix interferences. The method has been validated by analyzing two biota reference materials (ERM-CE477 mussel tissue and T-38 oyster tissue).


CHROMATOGRAPHY OF POLIOVIRUS ON CALCIUM PHOSPHATE AND ITS APPLICATION TO THE IDENTIFICATION OF VACCINE PROGENY STRAINS.
Ozaki, Yoshikatsu (Baylor University College of Medicine, Houston, Tex.), Arwin R. Diwan, Mizuho Takizawa, and Joseph L. Melnick. Chromatography of poliovirus on calcium phosphate and its application to the identification of vaccine progeny strains. J. Bacteriol. 89:603-610. 1965.-Virulent and attenuated polioviruses were studied chromatographically with calcium phosphate as adsorbent and neutral phosphate buffer as eluent. For type 1, the attenuated LSc2ab strain and the virulent Mahoney strain were eluted at different salt concentrations. The peak of elution for the LSc2ab strain was at 0.3 m, whereas for the Mahoney strain it was at 0.05 m. No differences in elution pattern were noted with virulent and attenuated strains of poliovirus types 2 and 3. Except for a single instance, progeny strains isolated from vaccines or contacts 1 to 8 weeks after vaccination showed an elution pattern similar to the parent vaccine strain, or intermediate between the virulent and attenuated strains but still clearly distinguishable from wild-type virus. A virus population that possessed the same elution property as the virulent Mahoney strain could be separated from a number of progeny strains by chromatography. The ratio of this easily eluted population appeared to increase during the course of multiplication of vaccine virus in the human intestine. A virus population with the same elution profile as Mahoney seems to be present in the current LSc2ab oral polio vaccine, but as a very minor component. However, this component could readily be enriched by selecting for passage only those virus particles eluted at low salt concentrations. Heat-resistant, attenuated virus strains were selected from virulent type 1 strains by the Wallis-Melnick procedure of repetitive heating of progeny in AlCl(3). However, the elution pattern remained the same as that of the parent virulent virus.


Yoga for epilepsy.
This is an updated version of the original Cochrane Review published in the Cochrane Library, Issue 5, 2015.Yoga may induce relaxation and stress reduction, and influence the electroencephalogram and the autonomic nervous system, thereby controlling seizures. Yoga would be an attractive therapeutic option for epilepsy if proved effective. To assess whether people with epilepsy treated with yoga:(a) have a greater probability of becoming seizure free;(b) have a significant reduction in the frequency or duration of seizures, or both; and(c) have a better quality of life. For this update, we searched the Cochrane Epilepsy Group Specialized Register (3 January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 12) in the Cochrane Library (searched 3 January 2017), MEDLINE (Ovid, 1946 to 3 January 2017), SCOPUS (1823 to 3 January 2017), ClinicalTrials.gov (searched 3 January 2017), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (searched 3 January 2017), and also registries of the Yoga Biomedical Trust and the Research Council for Complementary Medicine. In addition, we searched the references of all the identified studies. No language restrictions were imposed. The following study designs were eligible for inclusion: randomised controlled trials (RCT) of treatment of epilepsy with yoga. The studies could be double-, single- or unblinded. Eligible participants were adults with uncontrolled epilepsy comparing yoga with no treatment or different behavioural treatments. Two review authors independently assessed the trials for inclusion and extracted data. The following outcomes were assessed: (a) percentage of people rendered seizure free; (b) seizure frequency and duration; (c) quality of life. Analyses were on an intention-to-treat basis. Odds ratio (OR) with 95% confidence intervals (95% Cls) were estimated for the outcomes. We did not identify any new studies for this update, therefore the results are unchanged.For the previous version of the review, the authors found two unblinded trials in people with refractory epilepsy. In total these two studies included 50 people (18 treated with yoga and 32 to control interventions). Antiepileptic drugs were continued in all the participants. Baseline phase lasted three months in both studies and treatment phase from five weeks to six months in the two trials. Randomisation was by roll of a die in one study and using a computerised randomisation table in the other one but neither study provided details of concealment of allocation and were rated as unclear risk of bias. Overall, the two studies were rated as low risk of bias (all participants were included in the analysis; all expected and pre-expected outcomes were reported; no other sources of bias).The overall ORs with 95% CI were as follows: (i) seizure free for six months - for yoga versus sham yoga the OR was 14.54 (95% CI 0.67 to 316.69) and for yoga versus 'no treatment' group it was 17.31 (95% CI 0.80 to 373.45); for Acceptance and Commitment Therapy (ACT) versus yoga the OR was 1.00 (95% Cl 0.16 to 6.42); (ii) reduction in seizure frequency - the mean difference between yoga versus sham yoga group was -2.10 (95% CI -3.15 to -1.05) and for yoga versus 'no treatment' group it was -1.10 (95% CI -1.80 to -0.40); (iii) more than 50% reduction in seizure frequency - for yoga versus sham yoga group, OR was 81.00 (95% CI 4.36 to 1504.46) and for the yoga versus 'no treatment' group it was 158.33 (95% CI 5.78 to 4335.63); ACT versus yoga OR was 0.78 (95% Cl 0.04 to 14.75); (iv) more than 50% reduction in seizure duration - for yoga versus sham yoga group OR was 45.00 (95% CI 2.01 to 1006.75) and for yoga versus 'no treatment' group it was 53.57 (95% CI 2.42 to 1187.26); ACT versus yoga OR was 0.67 (95% Cl 0.10 to 4.35).In addition in Panjwani 1996 the authors reported that the one-way analysis of variance revealed no statistically significant differences between the three groups. A P-Lambda test taking into account the P values between the three groups also indicated that the duration of epilepsy in the three groups was not comparable. No data were available regarding quality of life. In Lundgren 2008 the authors reported that there was no significant difference between the yoga and ACT groups in seizure-free rates, 50% or greater reduction in seizure frequency or seizure duration at one-year follow-up. The yoga group showed significant improvement in their quality of life according to the Satisfaction With Life Scale (SWLS) (P < 0.05), while the ACT group had significant improvement in the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale (P < 0.01).Overall, we assessed the quality of evidence as low; no reliable conclusions can be drawn at present regarding the efficacy of yoga as a treatment for epilepsy. A study of 50 subjects with epilepsy from two trials reveals a possible beneficial effect in control of seizures. Results of the overall efficacy analysis show that yoga treatment was better when compared with no intervention or interventions other than yoga (postural exercises mimicking yoga). There was no difference between yoga and Acceptance and Commitment Therapy. However no reliable conclusions can be drawn regarding the efficacy of yoga as a treatment for uncontrolled epilepsy, in view of methodological deficiencies such as limited number of studies, limited number of participants randomised to yoga, lack of blinding and limited data on quality-of-life outcome. Physician blinding would normally be taken to be the person delivering the intervention, whereas we think the 'physician' would in fact be the outcome assessor (who could be blinded), so that would be a reduction in detection bias rather than performance bias. In addition, evidence to inform outcomes is limited and of low quality. Further high-quality research is needed to fully evaluate the efficacy of yoga for refractory epilepsy.Since we did not find any new studies, our conclusions remain unchanged.


Spinal cord precursors utilize neural crest cell mechanisms to generate hybrid peripheral myelinating glia.
During development, oligodendrocytes and Schwann cells myelinate central and peripheral nervous system axons, respectively, while motor exit point (MEP) glia are neural tube-derived, peripheral glia that myelinate axonal territory between these populations at MEP transition zones. From which specific neural tube precursors MEP glia are specified, and how they exit the neural tube to migrate onto peripheral motor axons, remain largely unknown. Here, using zebrafish, we found that MEP glia arise from lateral floor plate precursors and require foxd3 to delaminate and exit the spinal cord. Additionally, we show that similar to Schwann cells, MEP glial development depends on axonally derived neuregulin1. Finally, our data demonstrate that overexpressing axonal cues is sufficient to generate additional MEP glia in the spinal cord. Overall, these studies provide new insight into how a novel population of hybrid, peripheral myelinating glia are generated from neural tube precursors and migrate into the periphery.


On the creation of a segmentation library for digitized cervical and lumbar spine radiographs.
In this paper, we address the issue of computer-assisted indexing in one specific case, i.e., for the 17,000 digitized images of the spine acquired during the National Health and Nutrition Examination Survey (NHANES). The crucial step in this process is to accurately segment the cervical and lumbar spine in the radiographic images. To that end, we have implemented a unique segmentation system that consists of a suite of spine-customized automatic and semi-automatic statistical shape segmentation algorithms. Using the aforementioned system, we have developed experiments to optimally generate a library of spine segmentations, which currently include 2000 cervical and 2000 lumbar spines. This work is expected to contribute toward the creation of a biomedical Content-Based Image Retrieval system that will allow retrieval of vertebral shapes by using query by image example or query by shape example.


Gene flow creates a mirage of cryptic species in a Southeast Asian spotted stream frog complex.
Most new cryptic species are described using conventional tree- and distance-based species delimitation methods (SDMs), which rely on phylogenetic arrangements and measures of genetic divergence. However, although numerous factors such as population structure and gene flow are known to confound phylogenetic inference and species delimitation, the influence of these processes is not frequently evaluated. Using large numbers of exons, introns, and ultraconserved elements obtained using the FrogCap sequence-capture protocol, we compared conventional SDMs with more robust genomic analyses that assess population structure and gene flow to characterize species boundaries in a Southeast Asian frog complex (Pulchrana picturata). Our results showed that gene flow and introgression can produce phylogenetic patterns and levels of divergence that resemble distinct species (up to 10% divergence in mitochondrial DNA). Hybrid populations were inferred as independent (singleton) clades that were highly divergent from adjacent populations (7%-10%) and unusually similar (<3%) to allopatric populations. Such anomalous patterns are not uncommon in Southeast Asian amphibians, which brings into question whether the high levels of cryptic diversity observed in other amphibian groups reflect distinct cryptic species-or, instead, highly admixed and structured metapopulation lineages. Our results also provide an alternative explanation to the conundrum of divergent (sometimes nonsister) sympatric lineages-a pattern that has been celebrated as indicative of true cryptic speciation. Based on these findings, we recommend that species delimitation of continuously distributed "cryptic" groups should not rely solely on conventional SDMs, but should necessarily examine population structure and gene flow to avoid taxonomic inflation.


Participatory Design With Seniors: Design of Future Services and Iterative Refinements of Interactive eHealth Services for Old Citizens.
There is an increasing social isolation among the elderly today. This will be an even larger issue in the future with growing numbers of elderly and less resources, for example, in terms of economy and staff. Loneliness and social isolation can, however, be addressed in several ways using different interactive eHealth services. This case study investigated novel eHealth services for the elderly, and their usage of a social interactive device designed especially for them. In this work, we used an innovative mobile communication device connected to the television (TV), which worked as a remotely controlled large interactive screen. The device was tested by 8 volunteers who visited a senior center. They were between 65 and 80 years of age and lived in their own homes. Throughout the 1.5 year-long project, 7 design workshops were held with the seniors and the staff at the center. During these workshops, demands and preferences regarding existing and new services were gathered. At the end of the project the participants' experience of the device and of the services was elaborated in 3 workshops to get ideas for improved or new meaningful services. During the data analyses and development process, what seniors thought would be useful in relation to what was feasible was prioritized by the development company. Regarding daily usage, the seniors reported that they mainly used the service for receiving information from the senior center and for communication with other participants in the group or with younger relatives. They also read information about events at the senior center and they liked to perform a weekly sent out workout exercise. Further, they played games such as Memory and Sudoku using the device. The service development focused on three categories of services: cognitive activities, social activities, and physical activities. A cognitive activity service that would be meaningful to develop was a game for practicing working memory. In the social activities category, the seniors wanted different quizzes and multi-player games. For physical activities, the seniors desired more workout exercises and suggestions for guided walking routes. A new category, "information and news", was suggested since they lacked services like senior-customized global and local news. This study showed the importance of input from a group of seniors when designing new services for elderly citizens. Besides input to interactive eHealth service development for seniors, this study showed the importance of a social context around such work. The seniors were very engaged throughout the project and workshops were frequently visited and the seniors became friends. The high amount of input from the seniors could be explained in terms of social inclusion; they belonged to a group and each member was considered important for the work. The friendly workshop atmosphere facilitated new ideas and redesign of the services.


Late life changes in mental health: a longitudinal study of 9683 women.
To identify latent subgroups of women in late life who are alike in terms of their mental health trajectories. Longitudinal data are for 9683 participants in the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health, who completed at least two surveys between 1999 (aged 73-78 years) and 2008 (aged 82-87 years). Mental health was measured using the five-item mental health inventory (MHI-5). Latent profile analysis uncovered patterns of change in MHI-5 scores. Three patterns of change were identified for women who were still alive in 2008 (n = 7061), and three similar patterns for deceased women (n = 2622): (1) 'poor mental health' representing women with low MHI-5 scores, (2) 'good mental health' and (3) 'excellent' mental health, where scores remained very high. Deceased women had lower mental health scores for each class. Remote areas of residence, higher education, single marital status, higher Body Mass Index (BMI) and falls were the covariates associated with mental health in the survivor group. For the deceased group, education, BMI and falls were significant. Arthritis, stroke, heart disease, bronchitis/emphysema, diabetes and osteoporosis were associated with worse mental health for both groups, while asthma increased these odds significantly for the survivor group only. Hypertension and cancer were not significant predictors of poor mental health. The results show associations between chronic disease and level of mental health in older age, but no evidence of a large decline in mental health in the period prior to death.


Vitamin D and multiple sclerosis: where do we go from here?
This article briefly introduces the basics of multiple sclerosis' (MS) clinical hallmarks and pathophysiology. Vitamin D is presented, including its metabolism and effects on the immune system. The epidemiological observations linking vitamin D to MS range from a half century old findings of latitude gradients and migrational risk patterns to modern, nested, case-control biobank studies. These observations show an association without doubt although causation has yet to be proven. Vitamin D as a treatment for MS is an emerging concept and both current and anticipated data will be covered. Lastly, we discuss future challenges, ideas on how to move from association to causation, and the prospect of primary prevention of this disabling disease.


Using Patient Reported Outcomes Measures to Promote Integrated Care.
Patient reported outcome measures (PROMs) have been introduced as standardised outcomes, but have not been implemented widely for disease targeted pathways of care, nor for geriatric patients who prefer functional performance and quality of life. We describe innovative multipurpose implementation of PROMs as evidenced by two best practices of PROMs application in geriatric and physiotherapy practice. We show that PROMs can show meaningful outcomes in older subjects' patient journeys, which can at the same time serve individuals and groups of both patients and professionals. PROMs can deliver generic outcomes relevant for older patients, may improve patient-physician relationship, quality of care and prediction of future outcomes in geriatric care, if they are valid, reliable and responsive, but still short and simple. A precondition to make the hard tip from research to practice is that PROMs are carefully positioned in the clinical encounters and in electronic health records.


Antitoxin responses to Clostridium botulinum vaccines types C and D in guinea pigs.
In guinea pigs, the type C and/or type D antitoxin responses to a single dose of a bivalent or monovalent Cl. botulinum vaccine increase markedly between the fourth and ninth week after injection and still increase markedly by the ninth week. For type C, a similar pattern has been found in cattle. Antigens of types C and D mutually interfere with the antitoxin responses in guinea pigs. Graded doses of vaccine arouse graded antitoxin responses in guinea pigs. Stability trials of vaccines have emphasized the unsatisfactory nature of an absolute-response type of assay, rather than revealing any loss of potency during storage. Attention is drawn to the need for a graded-response type of assay in which vaccines under test are compared with a reference vaccine.


Epidermal cellular proliferation and differentiation in sexually mature male Salmo salar with androgen levels depressed by oil.
Sexually mature male Salmo salar exhibit epidermal thickening and an increase in goblet cell concentration during the spawning season. The ventral skin, which is likely to experience most abrasive contact during the spawning period, has the thickest epidermis and the greatest goblet cell concentration. Following exposure to crude oil there is inhibition of cellular proliferation and elongation associated with epidermal thickening, and also inhibition of mucigenesis. Data on the androgen levels in these fish, and data from earlier studies involving treatment with hormones, indicate that oil-related epidermal effects during the spawning period are most likely systemic in origin, probably arising from reduced plasmatic androgen levels.


A Developmental Study of Mathematics in Children with Autism Spectrum Disorder, Symptoms of Attention Deficit Hyperactivity Disorder, or Typical Development.
This study examined mathematics achievement in school-aged children with autism spectrum disorder (ASD), symptoms of attention-deficit/hyperactivity disorder (ADHD), or typical development (TD) over a 30-month period and the associations between cognitive and reading abilities with mathematics achievement in children with ASD. Seventy-seven children with ASD without intellectual disability (ASD-WoID), 39 children with ADHD, and 43 children with TD participated in this study. The results revealed that the ASD-WoID and ADHD samples displayed significant and comparable delays in problem solving and calculation abilities. Lower VIQ was related to lower math achievement across all subgroups. The ASD-WoID sample differed from comparison samples in terms of their pattern of mathematical achievement and the role of cognitive abilities in the development of mathematics competence.


Bidirectional but asymmetrical sexual hybridization between Brassica carinata and Sinapis arvensis (Brassicaceae).
With transgenic crop development it is important to evaluate the potential for transgenes to escape into populations of wild, weedy relatives. Ethiopian mustard (Brassica carinata, BBCC) is easily transformed and is being investigated for uses from biodiesel fuels to biopharmaceuticals. However, little work has been done evaluating its ability to cross with relatives such as wild mustard (Sinapsis arvensis, SrSr), an abundant, cosmopolitan weedy relative. Here we conducted bidirectional crosses with Ethiopian mustard as a maternal parent in 997 crosses and paternal parent in 1,109 crosses. Hybrids were confirmed using flow cytometry and species-specific ITS molecular markers and indicate a high hybridization rate of 6.43 % between Ethiopian mustard (♀) and wild mustard (♂) and a lower, but not insignificant, hybridization rate of 0.01 % in the reverse direction. The majority of the hybrids were homoploid (BCSr) with less than 1 % of pollen production of their parents and low seed production (0.26 seeds/pollination) in crosses and backcrosses indicating a potential for advanced generation hybrids. The accession used had a significant effect on hybrid seed production with different accessions of Ethopian mustard varying in their production of hybrid offspring from 2.69 to 16.34 % and one accession of wild mustard siring almost twice as many hybrid offspring per flower as the other. One pentaploid (BBCCSr) and one hexaploid (BBCCSrSr) hybrid were produced and had higher pollen viability, though no and low seed production, respectively. As wild mustard is self-incompatible and the outcrossing rate of Ethiopian mustard has been estimated as 30 % potential for hybrid production in the wild appears to be high, though the hybridization rate found here represents a worst case scenario as it does not incorporate pre-pollination barriers. Hybridization in the wild needs to be directly evaluated as does the propensity of Ethiopian mustard to volunteer.


Effects of a short abstinence period on sperm quality in oligozoospermic men.
The aim of this study was to compare semen parameters and sperm DNA fragmentation (SDF) and explore the relationship between semen parameters and SDF between 2 and 7 days of abstinence and a short abstinence period (within 4 hours) in oligozoospermic infertile patients. Two semen samples were collected from infertile oligozoospermic men (n=34) after an abstinence period of 2 to 7 days and within 4 hours, respectively. Sperm parameters were compared between the two abstinence duration groups, including semen volume, sperm concentration, total sperm count, sperm motility, total motile sperm count (TMSC), morphology, and SDF. The semen volume, concentration, and total sperm count were significantly decreased after 4 hours of abstinence than after 2 to 7 days of abstinence, with median differences of 1.2 mL (p<0.001), 2×106/mL (p=0.011), and 9.6×106/ejaculation (p<0.001), respectively. TMSC was significantly lower after a short abstinence, with a median difference of 4.24×106/ejaculate (p<0.001). However, there were no significance differences in the percentage of motility, the SDF, and the percentage of sperm with normal morphology. Interestingly, volume, concentration, total sperm count, sperm motility, and SDF, but not TMSC, exhibited significant linear correlations between the two abstinence groups in univariate regression analysis, except for TMSC. In oligozoospermic men, the volume, concentration, and total sperm count were significantly lower after a short abstinence period, but without adverse effects on sperm motility and SDF.


HIV-1 genetic diversity a challenge for AIDS vaccine development: a retrospective bibliometric analysis.
Despite recent advances in human immunodeficiency virus-1 (HIV-1) prevention, a fast, safe, and effective vaccine will probably be necessary to end the HIV/AIDS pandemic. This study was conducted to evaluate global research trends and map the key bibliometric indices in HIV-1 genetic diversity from 1998 to 2021. A comprehensive online search was conducted in the Web of Science Core Collection database to retrieve published literature on HIV-1 genetic diversity. Key bibliometric indicators were calculated and evaluated using HistCiteTM, Bibliometrix: An R-tool, and VOSviewer software for windows. A total of 2,060 documents written by 9,201 authors and published in 250 journals were included in the final analysis. Year 2012 was the most productive year with 121 (5.87%) publications. The most prolific author was Shao Yiming (n = 74, 3.59%) from Chinese Center for Disease Control and Prevention. The United States of America was the highly contributing and influential country (n = 681, 33.05%). AIDS Research and Human Retroviruses was the most productive journal (n = 562, 27.2%). Network visualization shows that HIV-1 was the most widely used author keyword. This study provides global research trends and detailed information on HIV-1 genetic diversity. The amount of scientific literature on HIV-1 genetic diversity research has rapidly increased in the last two decades. The maximum number of articles on HIV-1 genetic diversity was published in developed countries; therefore, a scientific research collaboration among researchers and institutes in low-income countries should be promoted and supported.


Easy to diagnose, difficult to treat: keratosis lichenoides chronica.
Keratosis lichenoides chronica (KLC) is a rare disease, with approximately 70 cases reported in the literature. The problem in this long-lasting disease is generally the treatment, not the diagnosis. In the literature, many treatments failed to show any beneficial effect. We present a 20-year-old man with KLC that was successfully treated with a combination of phototherapy, acitretin and calcipotriol ointment. The patient's lesions showed a marked improvement with this combination. To our knowledge, this is the first report of this type of combination treatment being used successfully in KLC. This approach might help reduce doses of retinoids or psoralen ultraviolet A required when these are used separately, and limit the potential toxicity of these treatments.


The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study.
Corticobasal degeneration (CBD) is a complex neurodegenerative disorder which nomenclature of which its nomenclature and characterization continues to evolve. The core clinical features that have been considered characteristic of the disorder include progressive asymmetric rigidity and apraxia, with other findings suggesting additional cortical (e.g., alien limb phenomena, cortical sensory loss, myoclonus, and mirror movements) and basal ganglionic (e.g., bradykinesia, dystonia, and tremor) dysfunctions. The characteristic findings at autopsy are asymmetric cortical atrophy that is typically maximal in the frontoparietal regions, as well as basal ganglia and nigral degeneration. Microscopically, abnormal accumulations of the microtubule-associated tau protein are found in both neurons and glia, and this disorder is now considered one of the "tauopathies." CBD was initially thought to represent a distinct clinicopathologic entity. Recent studies have shown considerable clinicopathologic heterogeneity, leading some to use the term "corticobasal syndrome" (CBS) for the constellation of findings initially considered characteristic of the disorder, and the term "corticobasal degeneration" for the histopathologic disorder. In this review, the multiple phenotypes/syndromes associated with CBD pathology, and multiple diseases associated with the CBS, are presented. The clinicopathologic heterogeneity in CBS/CBD and the implications of this heterogeneity on clinical practice, on understanding the focal/asymmetric cerebral degeneration syndromes, and on future research are all reviewed.


Treatment of advanced stage Hodgkin's disease.
Hodgkin's disease remains one of the few malignant diseases which can be cured by modern chemotherapy in most cases even in advanced stages. Adriamycin-containing chemotherapy regimens are considered as the standard therapy which induce long-term remission in about 60-70% of patients. The ABVD scheme, developed by Bonadonna and colleagues in Milan, has a favorable toxicity profile and causes less myelotoxicity, acute leukemia or sterility relative to many previous treatment programs containing alkylating agents. However, 20- 30 % of patients eventually relapse and are then frequently treated with high-dose programs including stem cell transplantation. There are two major goals in advanced Hodgkin's disease: (1) to improve the cure rate and (2) to reduce acute and long-term toxicities. The recent definition of prognostic factors identified patients who are at a high risk of treatment failure as well as those in whom less toxic approaches can be applied. The optimal approach or program has not yet been defined, although new chemotherapy regimens such as BEACOPP and Stanford V with increased tumor response rates have been identified. These new drug combinations are currently analyzed and compared with ABVD in several international trials. While the addition of radiotherapy improved disease control in some trials a survival benefit was not identified and the role of radiotherapy remains controversial. High dose programs remain experimental in advanced stage Hodgkin's disease and should be restricted to prospective clinical trials.


Across species-pool aggregation alters grassland productivity and diversity.
Plant performance is determined by the balance of intra- and interspecific neighbors within an individual's zone of influence. If individuals interact over smaller scales than the scales at which communities are measured, then altering neighborhood interactions may fundamentally affect community responses. These interactions can be altered by changing the number (species richness), abundances (species evenness), and positions (species pattern) of the resident plant species, and we aimed to test whether aggregating species at planting would alter effects of species richness and evenness on biomass production at a common scale of observation in grasslands. We varied plant species richness (2, 4, or 8 species and monocultures), evenness (0.64, 0.8, or 1.0), and pattern (planted randomly or aggregated in groups of four individuals) within 1 × 1 m plots established with transplants from a pool of 16 tallgrass prairie species and assessed plot-scale biomass production and diversity over the first three growing seasons. As expected, more species-rich plots produced more biomass by the end of the third growing season, an effect associated with a shift from selection to complementarity effects over time. Aggregating conspecifics at a 0.25-m scale marginally reduced biomass production across all treatments and increased diversity in the most even plots, but did not alter biodiversity effects or richness-productivity relationships. Results support the hypothesis that fine-scale species aggregation affects diversity by promoting species coexistence in this system. However, results indicate that inherent changes in species neighborhood relationships along grassland diversity gradients may only minimally affect community (meter) - scale responses among similarly designed biodiversity-ecosystem function studies. Given that species varied in their responses to local aggregation, it may be possible to use such species-specific results to spatially design larger-scale grassland communities to achieve desired diversity and productivity responses.


Effect of sawdust addition on composting of separated raw and anaerobically digested pig manure.
Manures need the addition of carbon-rich bulking agents to conserve N during composting, which increases the cost of the composting process. The recommended proportion of manure/sawdust, based on a carbon (C):nitrogen (N) ratio, is approximately 3:2. Two composting experiments were conducted to determine the impact of varying the proportion of sawdust to either separated raw, or separated anaerobically digested pig manures. To determine stability and maturity of the final compost, oxygen uptake rate (OUR) and germination index (GI) tests were conducted. For both experiments, three treatments were employed: manure-only (Treatment A), manure/sawdust mixed 4:1, fresh weight (Treatment B), and manure/sawdust mixed 3:2, fresh weight (Treatment C). The mixtures were composted in tumblers for 56 days with regular turning. The composting material was tested over the study duration for temperature, pH, water content, organic matter, C:N ratio and bulk density. For both Treatments B and C, the GI indicated low levels of phytotoxicity, and OUR values were lower than the recommended Irish threshold of 13 mmol O(2) kg OM(-1) h(-1), indicating that a high quality compost was produced. The proportion of sawdust to separated manure used can be reduced to make a cost saving, while still producing a stable end-product: 60% less sawdust is required to compost at a manure-to-sawdust ratio of 4:1 compared to the previously recommended ratio of 3:2.


A randomized controlled trial comparing the effects of Vitamin E, Ursodeoxycholic acid and Pentoxifylline on Egyptian non-alcoholic steatohepatitis patients.
Currently, no NASH-specific therapies are approved by the US Food and Drug Administration. This study aimed to compare the clinical effect of vitamin E (Vit. E), Ursodeoxycholic Acid (UDCA) and pentoxifylline (PTX) on Egyptian patients with NASH with exploration of their possible roles on inflammatory cytokines and chemokines mainly Interleukin 6 (IL6) and Monocyte Chemoattractant Protein-1 (CCL2/MCP-1). We conducted a 3-month, randomized, single-blind study in 102 Egyptian NASH patients who were divided into three groups; group 1 received Vit. E 400 mg twice a day, group 2 received UDCA 250 mg twice a day and group 3 received PTX 400 mg twice daily. Liver aminotransferases (AST, ALT), IL6, CCL2/MCP-1, albumin, bilirubin, and lipid panel were measured both before and after intervention intake. A significant decrease was found in liver aminotransferases, serum cytokine and chemokine in participants after Vit. E, UDCA or PTX intake. Compared to the UDCA and PTX groups, liver aminotransferases, serum cytokine and chemokine showed a more statistically significant reduction after Vit. E administration (50%, 43%, 57% and 55% for ALT, AST, IL6 and CCL2/MCP-1, respectively). In contrast, other biochemical tests showed non-significant change after any drug intake. None of the tested drugs showed significant safety issues in this population. Treatment with Vit. E, UDCA and PTX was both safe and effective in improving hepatic aminotransferases and inflammatory markers in Egyptian NASH patients. The superior effect of Vit. E compared to UDCA and PTX may suggest that oxidative stress plays a key role in disease progression of NASH patients. Moreover, IL6 and CCL2/MCP-1 may be used with or without ALT for treatment evaluation of NASH people.


Coronary CT Angiography: Variability of CT Scanners and Readers in Measurement of Plaque Volume.
Purpose To determine reader and computed tomography (CT) scan variability for measurement of coronary plaque volume. Materials and Methods This HIPAA-compliant study followed Standards for Reporting of Diagnostic Accuracy guidelines. Baseline coronary CT angiography was performed in 40 prospectively enrolled subjects (mean age, 67 years ± 6 [standard deviation]) with asymptomatic hyperlipidemia by using a 320-detector row scanner (Aquilion One Vision; Toshiba, Otawara, Japan). Twenty of these subjects underwent coronary CT angiography repeated on a separate day with the same CT scanner (Toshiba, group 1); 20 subjects underwent repeat CT performed with a different CT scanner (Somatom Force; Siemens, Forchheim, Germany [group 2]). Intraclass correlation coefficients (ICCs) and Bland-Altman analysis were used to assess interreader, intrareader, and interstudy reproducibility. Results Baseline and repeat coronary CT angiography scans were acquired within 19 days ± 6. Interreader and intrareader agreement rates were high for total, calcified, and noncalcified plaques for both CT scanners (all ICCs ≥ 0.96) without bias. Scanner variability was ±18.4% (coefficient of variation) with same-vendor follow-up. However, scanner variability increased to ±29.9% with different-vendor follow-up. The sample size to detect a 5% change in noncalcified plaque volume with 90% power and an α error of .05 was 286 subjects for same-CT scanner follow-up and 753 subjects with different-vendor follow-up. Conclusion State-of-the-art coronary CT angiography with same-vendor follow-up has good scan-rescan reproducibility, suggesting a role of coronary CT angiography in monitoring coronary artery plaque response to therapy. Differences between coronary CT angiography vendors resulted in lower scan-rescan reproducibility. © RSNA, 2016 Online supplemental material is available for this article.