Uterus preserving reposition of non-puerperal uterine inversion under laparoscope: a case report and literature review.
Non-puerperal uterine inversion is a rare clinical condition. Surgical procedures described in literature were mostly repositioning of the uterus followed by hysterectomy and laparotomy. In this paper, we reported a case of successful uterus preserving reposition of non-puerperal uterine inversion under laparoscopy. The patient, a 34-year-old, was presented with irregular vaginal bleeding with a mass protruding. On laparoscopy, the anterior wall of the uterus was opened longitudinally to release the thick ring of cervical tissue. The uterus was then repositioned and the anterior wall of the uterus was closed by stitches with two layers. Antibiotics was used for 6 days to prevent infection. The patient recovered well and retrieved menstruation 1 month after surgery.


Integrating High-Resolution and Solid-State Magic Angle Spinning NMR Spectroscopy and a Transcriptomic Analysis of Soybean Tissues in Response to Water Deficiency.
Solid-state NMR (SSNMR) spectroscopy methods provide chemical environment and ultrastructural details that are not easily accessible by other non-destructive, high-resolution spectral techniques. High-resolution magic angle spinning (HR-MAS) has been widely used to obtain the metabolic profile of a heterogeneous sample, combining the resolution enhancement provided by MAS in SSNMR with the shimming and locking procedures in liquid-state NMR. In this work, we explored the feasibility of using the HR-MAS and SSNMR techniques to identify metabolic changes in soybean leaves subjected to water-deficient conditions. Control and water-deficient soybean leaves were analysed using one-dimensional (1D) HR-MAS and SSNMR. Total RNA was extracted from the leaves for the transcriptomic analysis. The 1 H HR-MAS and CP-MAS 13 C{1 H} spectra of soybean leaves grown with and without water deficiency stress revealed striking differences in metabolites. A total of 30 metabolites were identified, and the impact of water deficiency on the metabolite profile of soybean leaves was to induce amino acid synthesis. High expression levels of genes required for amino acid biosynthesis were highly correlated with the compounds identified by 1 H HR-MAS. The integration of the 1 H HR-MAS and SSNMR spectra with the transcriptomic data provided a complete picture of the major changes in the metabolic profile of soybeans in response to water deficiency. Copyright © 2017 John Wiley & Sons, Ltd.


On the fate of seasonally plastic traits in a rainforest butterfly under relaxed selection.
Many organisms display phenotypic plasticity as adaptation to seasonal environmental fluctuations. Often, such seasonal responses entails plasticity of a whole suite of morphological and life-history traits that together contribute to the adaptive phenotypes in the alternative environments. While phenotypic plasticity in general is a well-studied phenomenon, little is known about the evolutionary fate of plastic responses if natural selection on plasticity is relaxed. Here, we study whether the presumed ancestral seasonal plasticity of the rainforest butterfly Bicyclus sanaos (Fabricius, 1793) is still retained despite the fact that this species inhabits an environmentally stable habitat. Being exposed to an atypical range of temperatures in the laboratory revealed hidden reaction norms for several traits, including wing pattern. In contrast, reproductive body allocation has lost the plastic response. In the savannah butterfly, B. anynana (Butler, 1879), these traits show strong developmental plasticity as an adaptation to the contrasting environments of its seasonal habitat and they are coordinated via a common developmental hormonal system. Our results for B. sanaos indicate that such integration of plastic traits - as a result of past selection on expressing a coordinated environmental response - can be broken when the optimal reaction norms for those traits diverge in a new environment.


Perspectives on Motivation and Change in an Intervention for Men Who Use Substances and Perpetrate Intimate Partner Abuse: Findings From a Qualitative Evaluation of the Advance Intervention.
Despite consistent evidence that substance use is a contributory risk factor for perpetration of intimate partner abuse (IPA), little evidence exists for effective interventions for male IPA perpetrators who use substances. The Advance intervention aimed to meet this need. This 16-week intervention addressed both IPA and substance use, and was for men accessing substance use treatment who had perpetrated IPA toward a female (ex-)partner within the last 12 months. Two key theories underpinned the intervention: goal theory and self-regulation theory. In this article, we aim to illustrate the views of men and substance use treatment staff on men's motivations to change, the ways in which men and staff said that men had changed their behavior, and the aspects of the intervention that they reported were key in the process of change. Using framework analysis, we analyzed data from 12 men who took part in the intervention as well as 31 staff members from substance use treatment services. Our five overarching themes were personal goal setting and motivation; recognition of IPA and the substance using lifestyle; improved self-regulation; considering the impact on others; and learning together in a group. Men and staff valued having a program that integrated IPA and substance use and thought the program was unique and much needed. Moreover, our findings suggest that goal theory, self-regulation, and more broadly, motivational and strengths-based approaches with practice-based activities, may be beneficial for effecting change in the substance using perpetrator population. However, further research is needed to determine the effectiveness of the intervention. Overall, our findings highlight the value of using qualitative outcome measures of perpetrator programs to complement quantitative measures of impact.


How do we avoid confounding the direction we are looking and the direction we are moving?
Contrary to a previous assumption, the center of the expanding pattern of visual flow is not generally useful as an aid in judging the direction of self motion since its direction depends on the direction of gaze. For some visual environments, however, the point of maximum rate of change of magnification in the retinal image coincides with the direction of self motion, independently of the direction of gaze. This visual indicator could be used to judge the direction of self motion.


Directional avoidance turns encoded by single interneurons and sustained by multifunctional serotonergic cells.
Avoidance turns in the sea slug Pleurobranchaea are responses to noxious stimuli and replace orienting turns to food stimuli after avoidance conditioning or satiation. Avoidance turns proved to be centrally patterned behaviors, the fictive expression of which could be elicited in reduced preparations and the isolated CNS. Activity in one of a bilateral interneuron pair, the A4 cells, was necessary and sufficient to drive the avoidance turn toward the contralateral side. Single A4 cells appeared to encode both turn direction and angle, in contrast to directional behaviors of other animals in which displacement angle is usually encoded by multiple units. The As1-4 cells, bilateral serotonergic cell clusters, excited the prolonged A4 burst during the turn through electrical and chemical coupling. However, during the escape swim, As1-4 became integral elements of the swim motor network, and A4 activity was entrained to the swim rhythm by alternating excitatory-inhibitory inputs, with only weak spiking. This provides a likely mechanism for the previously observed suppression of the avoidance turn by escape swimming. These observations add significant new aspects to the multiplying known functions of As1-4 and their homologs in other molluscs and point to a pivotal role of these neurons in the organization of gastropod behavior. Simple functional models predict (1) the essential actions of inhibitor neurons in the directionality of the turning network motor output and (2) an integrating role for As1-4 in the behavioral switch between turning avoidance and swimming escape, on the basis of their response to increasing stimulus intensity.


Inhibition of mechanosensory interneurons in the crayfish. I. Presynaptic inhibition from giant fibers.
1. Sucrose-gap and intracellular recordings were used to study the primary afferent depolarization (PAD) produced in mechanosensory afferents by impulses in lateral and medial giant axons, which are the command cells for the tail flip escape response in the crayfish. 2. The lateral and medial giant axons produce PAD through a polysynaptic interneuronal pathway. The response has a relatively long intraganglionic latency (7--11 ms), and command-evoked PAD can be recorded in ganglia from which the giant axons have been experimentally disconnected. 3. The final neurons of the pathway that delivers inhibition are few in number and extensive in distribution; most appear to be common to lateral and medial giant pathways. 4. At least some of the inhibitory interneurons have axons in the interganglionic connectives and probably produce both presynaptic and postsynaptic inhibition. 5. Stimulation of the lateral, but not the medial, giant axons causes a small, short-latency deplorization that is stable at high repetition rates. This small potential can be accounted for by transmission across known electrical synapses between mechanosensory afferents and the lateral giants in each abdominal ganglion. 6. Repetitive stimulation of the lateral giant axons causes substantial augmentation of PAD, apparently through recruitment of additional interneurons. PAD evoked by a single medial giant (MG) stimulus is generally much larger than that elicited by a single lateral giant (LG) spike. However, MG-PAD summates little and so the maximum PAD deltaV reached during repetitive firing is equivalent for the two types of giant axons. 7. Iontophoresis of gamma-aminobutyric acid (GABA) into the ganglionic neuropil depolarizes the primary afferents and blocks activity in neurons that have axons in the interganglionic connective. 8. The extrapolated PAD reversal potential and pharmacological studies suggest that a GABA-mediated chloride conductance increase is involved in the production of PAD.


The feasibility of concentrated rural settlement in a context of post-disaster reconstruction: a study of China.
There is growing appreciation of the use of concentrated rural settlement as an effective means of implementing infrastructure projects and helping to achieve sustainable development in rural areas. This occurs in China through the exchange of rural residential land for urban construction. However, this policy has not been effective under normal circumstances (called development-driven conditions) as frequently farmers are reluctant to accept such an exchange. By contrast, in a time of disaster, such as after the 2008 earthquake in Sichuan Province, China, rural victims have accepted this policy of rural residential land exchange. Employing game theory, this paper identifies the reasons for the different outcomes and it contends that the implementation of concentrated rural settlement practice under disaster-induced conditions is more effective than its introduction under development-driven conditions. The results of the analysis indicate that, in China, concentrated rural settlement is feasible in a context of post-disaster reconstruction.


[Abdominal aortic aneurysm--is a conservative attitude still justified? Experiences with 56 emergency and 128 elective surgical patients from the anesthesiological and vascular surgery viewpoints].
A retrospective analysis was undertaken of a consecutive series of 184 patients operated on between 1.1. 1984 and 31. 12. 1985 for aneurysm of the abdominal aorta. Rupture of the aneurysm had occurred in 56 patients (aged 70 +/- 9 yrs), 47 (aged 66 +/- 9 yrs) had symptoms of an aneurysm, and 81 (aged 66 +/- 5 yrs) were operated on electively. The highest peri-operative hospital mortality rate, of 35.9%, was among the group with rupture (compared with 8.5% for the symptomatic group and 1.2% for the elective one). The period of intensive care in surviving patients was highest in the rupture group, at 8 +/- 17 days, compared with 3 +/- 2 in the symptomatic and 3 +/- 3 days in the elective group. Duration of postoperative hospital stay was 20 +/- 13, 15 +/- 7 and 13 +/- 6 days, respectively, in the three groups. Half of the patients also had arterial obstructive disease, arterial hypertension and/or coronary heart disease (25% had had an infarct according to the history, 8% more than one). A third of the patients received or should have received treatment for lung or respiratory tract disease, heart failure and/or cardiac arrhythmias. The thirty-fold increase in mortality rate for an emergency operation over that for elective surgery, together with the higher costs and longer hospital treatment, as well as the reduced probability of survival with conservative treatment speak for an aggressive approach towards elective surgery after optimal pre-operative treatment.


Salt-concentration-dependent nucleation rates in low-metastability colloidal charged sphere melts containing small amounts of doublets.
We determined bulk crystal nucleation rates in aqueous suspensions of charged spheres at low metastability. Experiments were performed in dependence on electrolyte concentration and for two different particle number densities. The time-dependent nucleation rate shows a pronounced initial peak, while postsolidification crystal size distributions are skewed towards larger crystallite sizes. At each concentration, the nucleation rate density initially drops exponentially with increasing salt concentration. The full data set, however, shows an unexpected scaling of the nucleation rate densities with metastability times the number density of particles. Parameterization of our results in terms of classical nucleation theory reveals unusually low interfacial free energies of the nucleus surfaces and nucleation barriers well below the thermal energy. We tentatively attribute our observations to the presence of doublets introduced by the employed conditioning technique. We discuss the conditions under which such small seeds may induce nucleation.


Clinical and MRI phenotypes of sarcoidosis-associated myelopathy.
To determine the characteristic clinical and spinal MRI phenotypes of sarcoidosis-associated myelopathy (SAM), we analyzed a large cohort of patients with this disorder. Patients diagnosed with SAM at a single center between 2000 and 2018 who met the established criteria for definite and probable neurosarcoidosis were included in a retrospective analysis to identify clinical profiles, CSF characteristics, and MRI lesion morphology. Of 62 included patients, 33 (53%) were male, and 30 (48%) were African American. SAM was the first clinical presentation of sarcoidosis in 49 patients (79%). Temporal profile of symptom evolution was chronic in 81%, with sensory symptoms most frequently reported (87%). CSF studies showed pleocytosis in 79% and CSF-restricted oligoclonal bands in 23% of samples tested. Four discrete patterns of lesion morphology were identified on spine MRI: longitudinally extensive myelitis (n = 28, 45%), short tumefactive myelitis (n = 14, 23%), spinal meningitis/meningoradiculitis (n = 14, 23%), and anterior myelitis associated with areas of disc degeneration (n = 6, 10%). Postgadolinium enhancement was seen in all but 1 patient during the acute phase. The most frequent enhancement pattern was dorsal subpial enhancement (n = 40), followed by meningeal/radicular enhancement (n = 23) and ventral subpial enhancement (n = 12). In 26 cases (42%), enhancement occurred at locations with coexisting structural changes (e.g., spondylosis). Recognition of the clinical features (chronically evolving myelopathy) and distinct MRI phenotypes (with enhancement in a subpial and/or meningeal pattern) seen in SAM can aid diagnosis of this disorder. Enhancement patterns suggest that SAM may have a predilection for areas of the spinal cord susceptible to mechanical stress.


Decreased pituitary growth hormone content in rats treated neonatally with high doses of L-thyroxine.
Growth hormone and thyrotrophic hormone content have been measured by specific radioimmunoassays in anterior pituitaries of 22 day old rats. These animals were injected with saline or very high doses of L-thyroxine during the neonatal period in order to induce the "neo-T4" syndrome. Growth of such animals is known to be affected. It was found that not only TSH but also GH content of the T4-treated animals was significantly lower than that of the saline-injected controls.


Chromosomal Translocation Formation Is Sufficient to Produce Fusion Circular RNAs Specific to Patient Tumor Cells.
Circular RNAs constitute a unique class of RNAs whose precise functions remain to be elucidated. In particular, cancer-associated chromosomal translocations can give rise to fusion circular RNAs that play a role in leukemia progression. However, how and when fusion circular RNAs are formed and whether they are being selected in cancer cells remains unknown. Here, we used CRISPR/Cas9 to generate physiological translocation models of NPM1-ALK fusion gene. We showed that, in addition to generating fusion proteins and activating specific oncogenic pathways, chromosomal translocation induced by CRISPR/Cas9 led to the formation of de novo fusion circular RNAs. Specifically, we could recover different classes of circular RNAs composed of different circularization junctions, mainly back-spliced species. In addition, we identified fusion circular RNAs identical to those found in related patient tumor cells providing evidence that fusion circular RNAs arise early after chromosomal formation and are not just a consequence of the oncogenesis process.


Physicochemical and kinetic properties of unique isozymes of UDP-Glc pyrophosphorylase that are associated with resistance to sweetening in cold-stored potato tubers.
Isozymes of UGPase with unique catalytic properties were purified from the cold-induced-sweetening (CIS) resistant cultivar Snowden (Solanum tuberosum). Two distinct peaks of UGPase activity were obtained when protein extracts were subjected to anion-exchange chromatography on DEAE-Sephacel. Polypeptides in the first eluted fraction (A-I) were ionically similar to the UGPase isozyme UGP3 previously purified and characterized from the cold-sweetening sensitive cultivar Norchip (Sowokinos et al. 1993, Plant Physiol 101: 1073-1080). Seventy-two percent of the total endogenous UGPase activity in Snowden (cv.) tubers, however, was found in a more basic protein fraction (A-II) that is not found in the Norchip cultivar. This study reports on the physicochemical and kinetic properties of these new polypeptides that demonstrate UGPase activity. The reaction in the direction of UDP-Glc synthesis was specific for the substrates Glc-1-P and UTP and there was an absolute requirement for Mg2+ ions. The catalytic properties of UGP5 were markedly different from UGPase isozymes previously described in terms of (1) affinity for the substrate Glc-1-P, (2) pH optimum, (3) maximum reaction velocity and (4) sensitivity to product inhibition with UDP-Glc. Chi-square analysis of fifty-four genetically diverse potato lines revealed that resistance to CIS was highly correlated with the presence of the A-II isozymes of UGPase. The kinetic properties of these unique forms of UGPase may underlie, in part, a tuber's ability to resist sweetening in the cold.


Inhibition of the DNA-binding and transcriptional repression activity of the Wilms' tumor gene product, WT1, by cAMP-dependent protein kinase-mediated phosphorylation of Ser-365 and Ser-393 in the zinc finger domain.
The Wilms' tumor suppressor gene, WT1, encodes a transcription factor in the zinc finger family, which binds to GC-rich sequences and functions as a transcriptional activator or repressor. The WT1 protein plays a crucial role in urogenital development in mammals and its function is thought to be conserved during vertebrate evolution. Although accumulating evidence suggests that WT1 regulates a subset of genes including growth factor and growth factor receptor genes, little is known about regulators or signal cascades that could modulate the function of WT1. In this study, we show that the WT1 protein expressed exogenously in fibroblasts was phosphorylated in vivo, and that treatment with forskolin, which activates the cAMP-dependent protein kinase (PKA) in vivo, induced phosphorylation of additional sites in WT1. We identified the forskolin-induced phosphorylation sites as Ser-365 and Ser-393, which lie in the zinc finger domain in zinc fingers 2 and 3, respectively. PKA phosphorylated WT1 at Ser-365 and Ser-393 in vitro, as well as at additional sites, and this phosphorylation abolished the DNA-binding activity of WT1 in vitro. Using WT1 mutants in which Ser-365 and Ser-393 were mutated to Ala individually and in combination, we showed that phosphorylation of these sites was critical for inhibition of DNA binding in vivo. Thus, coexpression of the PKA catalytic subunit with wild type WT1 reduced the level of WT1 DNA-binding activity detected in nuclear extracts, and decreased transcriptional repression activity in vivo. In contrast to wild type WT1, all of the phosphorylation site mutants retained significant DNA-binding activity and repression activity in the presence of PKA. Analysis of the mutants showed that phosphorylation of Ser-365 and Ser-395 had additive inhibitory effects on WT1 DNA-binding in vivo and that phosphorylation at both sites was required for neutralization of repression activity. Therefore, we conclude that PKA modulates the activity of WT1 in vivo through phosphorylation of Ser-365 and Ser-393, which inhibits DNA binding. This in turn results in a decrease in WT1 transcriptional repression. Our findings provide the first evidence that the function of WT1 can be modulated by its phosphorylation in vivo.


Communicating about medications during primary care outpatient visits: the role of electronic medical records.
To assess the role of electronic medical records (EMR) in facilitating the content and process of patient-provider exchanges about medications during outpatient primary care visits. Fifty encounters with six physicians using the EMR were videotaped, transcribed and content-analysed by applying conversation analysis and ethnomethodology techniques. The analysis focused on three aspects of medication communication: (1) process of care: practices by patients and physicians to implement medication decisions; (2) themes: medication topics that consistently emerge; and (3) names: ways patients and physicians refer to medications. In-depth analysis of 20 encounters examined the extent to which either or both parties initiated, expanded and concluded medication discussions. On average 21.2 (range: 8-35; SD=7.4) distinct exchanges per encounter were observed. Of those, 33% were related to medication. Of the 350 medication-related exchanges throughout the encounters, 56% were categorised as routine medication discussion such as ordering and/or refilling medications. Mailing issues were the next most common medication-related exchanges (10.6%), followed by partial adherence (8.9%), self-regulation (7.4%), alternative therapy/over-the-counter medication (6.6%), side effects (6%) and formulary issues (4.6%). Patients and providers used three ways to name medications: generic/scientific name (42%); physical description (39.7%) and brand name (18.3%). Forty-one percent of exchanges included initiation by one or both parties but no further discussion of the issue; 42% included initiation and expansion by both parties but not conclusion; only 17% of exchanges contained complete medication exchanges (initiation, expansion and conclusion) by both parties. EMR facilitated content and process of communication regarding medications during outpatient encounters, especially among patients taking multiple medications and patients who used physical descriptions to identify their medications. EMR use stimulated medication exchanges, leading to further expansion about the topic. However, fewer than one-fifth of exchanges ended with clear conclusions by both parties regarding prescribed medication regimens.


Assessing the impact of orphanhood on Thai children affected by AIDS and their caregivers.
The implications of orphanhood for AIDS-affected children in Thailand is a subject which has received little scholarly attention despite the intensity and longevity of the epidemic in that country. The present study presents preliminary findings from a longitudinal investigation of the circumstances and welfare of Thai youth who have lost one or both parents to AIDS-related causes and the families who care for them. Based on interviews and focus groups carried out in Chiang Mai province in 2001-2002, the study finds that most of the children left orphaned by AIDS were being cared for by members of their extended family, especially grandparents or maternal aunts, and that many caregiving households were experiencing significant financial hardship which might have implications for the children's long-term well-being and stability and for their opportunities for educational advancement. Concern were also expressed about the unavailability or inaccessibility of childcare for AIDS-affected children and the perceived instability of fostering arrangements which placed young children in the care of elderly relatives.


The role of voluntary exercise in enriched rearing: a behavioral analysis.
The effects of postweaning enriched rearing and home cage voluntary wheel-running exercise in adulthood were contrasted on a comprehensive battery of tests designed to assess mnemonic, attentional, emotional, and motor functions. In a 2 x 2 factorial design, female C57BL/6 mice were housed in groups in either standard or enriched cages, which were equipped with either a running or a locked wheel. They were maintained in the corresponding housing conditions for 2 months postweaning prior to, and throughout, testing. Enriched rearing was associated with anxiogenesis, hypolocomotor activity, enhanced motor skills, retarded extinction of conditioned responding, and improved water maze performance. Exercise as such enhanced motor coordination and facilitated extinction of contextual conditioning. Evidence for an interaction between enrichment and exercise was apparent in the open field test, conditioned freezing to a tone stimulus, prepulse inhibition, and acquisition of water maze reference memory. Hence, care should be taken to control for the unique contribution of wheel-running exercise when it is included as an integral component of the enrichment procedure.


Ethics in epidemiological research.
This text focus, on a series of author's opinions, on the difficulties that the current system of regulation of ethics in research represents for the practice of the epidemiological research, in the Country. It introduces a few understandings concerning the present subject in the international literature, pointing out some of the most relevant themes and problems. It also examines part of the difficulties faced by Brazilian epidemiologists. The main topic developed in the article is the specificity of the science's reasoning that guides acting of the public health and epidemiology with repercussions for the practice of scientific research in this field, plenty different from the science's reasoning that preside medical practice and biomedical research. Hence the inadequacy of the ethical recommendations in force, all of them based on biomedical research, particularly at that with experimental design. It concludes with the indication that procedures adopted by the system of the ethics in research should be reviewed, adapting such procedures to the characteristics of different kinds of research.


Co-culture of a Novel Fermentative Bacterium, Lucifera butyrica gen. nov. sp. nov., With the Sulfur Reducer Desulfurella amilsii for Enhanced Sulfidogenesis.
Biosulfidogenesis can be used to remediate low pH and high metal content waters such as acid mine drainage and recover the present metals. The selection of a cheap electron donor for the process is important for the economic viability. In this work we isolated a novel versatile acidotolerant fermentative bacterium (strain ALET) that is able to use a great variety of substrates including glycerol. Strain ALET is an obligate anaerobe, and cells are motile, rod-shaped, spore-forming, and stain Gram-positive. Growth occurred in a pH range from 3.5 to 7 (optimum 5.5), and temperature range from 25 to 40°C (optimum 37°C). It grows by fermentation of sugars, organic acids and glycerol. It has the ability to use thiosulfate, iron and DMSO as electron acceptors. Its genome is 4.7 Mb with 5122 protein-coding sequences, and a G+C content of 46.9 mol%. Based on 16S rRNA gene sequence analysis, the closest cultured species is Propionispora hippei (91.4% 16S rRNA gene identity) from the Sporomusaceae family (Selenomonadales order, Negativicutes class, Firmicutes phylum). Based on the distinctive physiological and phylogenetic characteristics of strain ALET, a new genus and species Lucifera butyrica gen. nov., sp. nov., is proposed. The type strain is ALET (=JCM 19373T = DSM 27520T). Strain ALET is an incomplete oxidizer and acetate, among other products, accumulates during glycerol conversion. Strain ALET was used to extend the substrate range for sulfur reduction by constructing co-cultures with the acetate oxidizer and sulfur reducer Desulfurella amilsii. The co-culture was tested with glycerol as substrate in batch and chemostat experiments. Acetate formed by fermentation of glycerol by strain ALET resulted in sulfur reduction by D. amilsii. The co-culture strategy offers good perspectives to use a wide range of cost-efficient substrates, including glycerol, to produce sulfide by specialized sulfur reducers. The recovery of heavy metals from metalliferous streams may become economically feasible by this approach. Note: The locus tag for the genes encoded in Lucifera butyrica is LUCI_∗. To avoid repetition of the prefix along the text, the locus tags are represented by the specific identifier.


Ferrule-Effect Dominates Over Use of a Fiber Post When Restoring Endodontically Treated Incisors: An In Vitro Study.
The aim of this study was to investigate the restoration of broken-down endodontically treated incisors with the ferrule effect using glass ceramic crowns bonded to composite resin core buildups with or without a fiber post. A no-ferrule group with post was also included for comparison. Thirty decoronated endodontically treated bovine incisors with a 2-mm ferrule were restored with a direct buildup using a nanohybrid direct composite resin (Miris 2 and Optibond FL) with or without a glass-fiber-reinforced post. An additional group of 15 teeth without a ferrule were restored with buildup and a fiber post. All teeth were prepared to receive bonded glass ceramic crowns (e.max CAD luted with Variolink Esthetic DC) and were subjected to accelerated fatigue testing. Cyclic isometric loading was applied to the incisal edge at an angle of 30° and a frequency of 5 Hz, beginning with a load of 100 N (×5000 cycles). A 100 N load increase was applied each 15,000 cycles. Specimens were loaded until failure or to a maximum of 1000 N (×140,000 cycles). Groups were compared using the Kaplan Meier survival analysis (log rank test at p=0.05). None of the tested specimens withstood all 140,000 load cycles. Specimens with posts but without a ferrule were affected by an initial failure phenomenon (wide gap at the lingual margin between the buildup/crown assembly and the root). There was a significant difference in mean survived cycles between the ferrule groups (Fp=73,332× and FNp=73,244×) and the no-ferrule group (50,121×; p=0.001). The addition of a fiber post was not significant in the presence of the ferrule (p=0.884). In both groups with posts, 100% of failures were unrestorable. The no-post group had 47% of restorable and possibly restorable failures. The survival of broken-down nonvital incisors was improved by the presence of the ferrule but not by the fiber-reinforced post. Fiber posts were always detrimental to the failure mode and were not able to compensate for the absence of a ferrule.


Epigenetic regulation of drug transporter expression in human tissues.
Drug transporters are expressed in a number of tissues such as the intestine, liver, and kidney, and play key roles in drug absorption, distribution, and excretion. Variations in drug transporter gene expression significantly contribute to interindividual differences in drug responses. Epigenetic regulation of drug transporter genes has recently emerged as an important mechanism. Epigenetic regulation alters the expression of genes without changing DNA sequences. Epigenetic control mechanisms are associated with DNA methylation, histone modifications, and microRNAs. Herein we discuss recent advances in the study of the transcriptional and post-transcriptional mechanisms of drug transporters with a focus on epigenetic regulation. Areas covered: This review summarizes recent research on the epigenetic regulation of drug transporter genes, and highlights the importance of identifying novel biomarkers based on epigenetics for use in individualized drug therapy. Expert opinion: Researchers are actively attempting to elucidate the epigenetic mechanisms that control the expression of drug transporters, which affect the pharmacokinetics of drugs. Current evidence suggests that epigenetic changes play an important role in drug transporter function. A clearer understanding of epigenetic regulation in drug transporter genes will provide an insight into novel approaches to individualized drug therapy.


Telerobotic neurovascular interventions with magnetic manipulation.
Advances in robotic technology have been adopted in various subspecialties of both open and minimally invasive surgery, offering benefits such as enhanced surgical precision and accuracy with reduced fatigue of the surgeon. Despite the advantages, robotic applications to endovascular neurosurgery have remained largely unexplored because of technical challenges such as the miniaturization of robotic devices that can reach the complex and tortuous vasculature of the brain. Although some commercial systems enable robotic manipulation of conventional guidewires for coronary and peripheral vascular interventions, they remain unsuited for neurovascular applications because of the considerably smaller and more tortuous anatomy of cerebral arteries. Here, we present a teleoperated robotic neurointerventional platform based on magnetic manipulation. Our system consists of a magnetically controlled guidewire, a robot arm with an actuating magnet to steer the guidewire, a set of motorized linear drives to advance or retract the guidewire and a microcatheter, and a remote-control console to operate the system under real-time fluoroscopy. We demonstrate our system's capability to navigate narrow and winding pathways both in vitro with realistic neurovascular phantoms representing the human anatomy and in vivo in the porcine brachial artery with accentuated tortuosity for preclinical evaluation. We further demonstrate telerobotically assisted therapeutic procedures including coil embolization and clot retrieval thrombectomy for treating cerebral aneurysms and ischemic stroke, respectively. Our system could enable safer and quicker access to hard-to-reach lesions while minimizing the radiation exposure to physicians and open the possibility of remote procedural services to address challenges in current stroke systems of care.


Survey on female genital mutilation/cutting in Jeddah, Saudi Arabia.
The objective of this study was to determine whether female genital mutilation/cutting (FGM/C) exists in Jeddah, Saudi Arabia. A cross-sectional study. King Abdulaziz University Hospital, Jeddah, Saudi Arabia. Between December 2016 and August 2017, women attending the obstetrics and gynaecology clinics were asked to participate in a cross-sectional survey. This included questions on demographics, FGM/C status and type and attitudes towards the practice. In a convenience sample of 963 women aged 18 to 75 years, 175 (18.2%) had undergone FGM/C. Compared with women without FGM/C, women with FGM/C were older, married, non-Saudi and had a lower monthly income. Thirty-seven (21.1%) women had had FGM/C with some cutting of body parts (type I or II), 11 (6.3%) with suturing (type III), 46 (26.3%) with no cutting of body parts (type IV) and 81 (46.3%) did not know their type of FGM/C. There was also a significant association between nationality and age at which FGM/C was performed, with Saudi women undergoing the procedure earlier than Egyptian, Somali, Yemeni and Sudanese women. FGM/C is prevalent in Jeddah, Saudi Arabia, among immigrant women from other countries, and it is practised among Saudi women. Further research is needed to determine its prevalence.


A novel baseline-correction method for standard addition based derivative spectra and its application to quantitative analysis of benzo(a)pyrene in vegetable oil samples.
In the present work, a baseline-correction method based on peak-to-derivative baseline measurement was proposed for the elimination of complex matrix interference that was mainly caused by unknown components and/or background in the analysis of derivative spectra. This novel method was applicable particularly when the matrix interfering components showed a broad spectral band, which was common in practical analysis. The derivative baseline was established by connecting two crossing points of the spectral curves obtained with a standard addition method (SAM). The applicability and reliability of the proposed method was demonstrated through both theoretical simulation and practical application. Firstly, Gaussian bands were used to simulate 'interfering' and 'analyte' bands to investigate the effect of different parameters of interfering band on the derivative baseline. This simulation analysis verified that the accuracy of the proposed method was remarkably better than other conventional methods such as peak-to-zero, tangent, and peak-to-peak measurements. Then the above proposed baseline-correction method was applied to the determination of benzo(a)pyrene (BaP) in vegetable oil samples by second-derivative synchronous fluorescence spectroscopy. The satisfactory results were obtained by using this new method to analyze a certified reference material (coconut oil, BCR(®)-458) with a relative error of -3.2% from the certified BaP concentration. Potentially, the proposed method can be applied to various types of derivative spectra in different fields such as UV-visible absorption spectroscopy, fluorescence spectroscopy and infrared spectroscopy.


Chronic pain among children and adolescents: physician consultation and medication use.
The goal of this study was to assess physician consultation and use of medication in Dutch children and adolescents (0-18 years old) having chronic pain in relation to sociodemographic factors and pain characteristics. This was a population-based cross-sectional survey. A questionnaire was either mailed to the participants' parents or distributed at school, and it was filled out by the parents (for children aged 0-7 years) or by the participant (for children and adolescents aged 8-18 years). The study was conducted in the Rotterdam area. Participants included a random sample of 1,300 children aged 0 to 3 years taken from the register of population. In addition, 41 schools were selected to obtain a representative sample of 5,336 children and adolescents aged 4 to 18 years. Reported physician consultation and medication use were assessed. Of the 6,636 children and adolescents surveyed, 5,424 (82%) responded. A total of 1,358 respondents (25%) reported chronic pain. Of these, 57% had consulted a physician and 39% had used medication for the pain. Respondents with earache, more intense pain, and more frequent pain and those attending lower vocational training programs were more likely to consult a physician for the pain than the average respondent. Respondents with earache, sore throat, headache, more intense pain, and multiple pain; children aged 0 to 3 years; and girls were more likely to use medication for the pain. Logistic regression analyses showed that for physician consultation, the most significant predictive factors were the intensity of pain, age, and earache as well as the level of education for respondents aged 12 to 16 years. The use of medication was predicted by earache, headache, limb pain, intensity of pain, and age. Chronic pain is a common complaint in children and adolescents, frequently resulting in consultation of a physician and medication use. Regarding physician consultation, children and adolescents with a lower educational level seem to be a group at risk.


The cigar revival and the popular press: a content analysis, 1987-1997.
The purpose of this study was to examine print media coverage of cigars during the period 1987 to 1997. A content analysis of 790 cigar-focused newspaper and magazine articles was conducted. Cigar-focused articles increased substantially over the study period, paralleling increased cigar consumption. Articles focused on cigar business (39%) and events (19%). Only 4% of articles focused on health effects. Sixty-two percent portrayed cigars favorably. The tobacco industry was mentioned in 54% of articles and portrayed positively in 78%. Forty-two percent of the individuals quoted or described in articles were affiliated with the tobacco industry; only 5% were government/public health figures. Print coverage of cigars failed to communicate health risk messages and contributed to positive images of cigars.


Subolesin expression in response to pathogen infection in ticks.
Ticks (Acari: Ixodidae) are vectors of pathogens worldwide that cause diseases in humans and animals. Ticks and pathogens have co-evolved molecular mechanisms that contribute to their mutual development and survival. Subolesin was discovered as a tick protective antigen and was subsequently shown to be similar in structure and function to akirins, an evolutionarily conserved group of proteins in insects and vertebrates that controls NF-kB-dependent and independent expression of innate immune response genes. The objective of this study was to investigate subolesin expression in several tick species infected with a variety of pathogens and to determine the effect of subolesin gene knockdown on pathogen infection. In the first experiment, subolesin expression was characterized in ticks experimentally infected with the cattle pathogen, Anaplasma marginale. Subolesin expression was then characterized in questing or feeding adult ticks confirmed to be infected with Anaplasma, Ehrlichia, Rickettsia, Babesia or Theileria spp. Finally, the effect of subolesin knockdown by RNA interference (RNAi) on tick infection was analyzed in Dermacentor variabilis males exposed to various pathogens by capillary feeding (CF). Subolesin expression increased with pathogen infection in the salivary glands but not in the guts of tick vector species infected with A. marginale. When analyzed in whole ticks, subolesin expression varied between tick species and in response to different pathogens. As reported previously, subolesin knockdown in D. variabilis infected with A. marginale and other tick-borne pathogens resulted in lower infection levels, while infection with Francisella tularensis increased in ticks after RNAi. When non-tick-borne pathogens were fed to ticks by CF, subolesin RNAi did not affect or resulted in lower infection levels in ticks. However, subolesin expression was upregulated in D. variabilis exposed to Escherichia coli, suggesting that although this pathogen may induce subolesin expression in ticks, silencing of this molecule reduced bacterial multiplication by a presently unknown mechanism. Subolesin expression in infected ticks suggested that subolesin may be functionally important for tick innate immunity to pathogens, as has been reported for the akirins. However, subolesin expression and consequently subolesin-mediated innate immunity varied with the pathogen and tick tissue. Subolesin may plays a role in tick innate immunity in the salivary glands by limiting pathogen infection levels, but activates innate immunity only for some pathogen in the guts and other tissues. In addition, these results provided additional support for the role of subolesin in other molecular pathways including those required for tissue development and function and for pathogen infection and multiplication in ticks. Consequently, RNAi experiments demonstrated that subolesin knockdown in ticks may affect pathogen infection directly by reducing tick innate immunity that results in higher infection levels and indirectly by affecting tissue structure and function and the expression of genes that interfere with pathogen infection and multiplication. The impact of the direct or indirect effects of subolesin knockdown on pathogen infection may depend on several factors including specific tick-pathogen molecular interactions, pathogen life cycle in the tick and unknown mechanisms affected by subolesin function in the control of global gene expression in ticks.


Akt1 signaling coordinates BMP signaling and β-catenin activity to regulate second heart field progenitor development.
Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract. Cell proliferation of cardiac progenitors was enhanced, whereas cardiac differentiation was unaffected by Pten deletion. Removal of Akt1 rescued the phenotype and early lethality of Pten deletion mice, suggesting that Akt1 was the key downstream target that was negatively regulated by PTEN in cardiac progenitors. Furthermore, we found that inhibition of FOXO by Akt1 suppressed the expression of the gene encoding the BMP ligand (BMP7), leading to dampened BMP signaling in the hearts of Pten deletion mice. Cardiac activation of Akt also increased the Ser552 phosphorylation of β-catenin, thus enhancing its activity. Reducing β-catenin levels could partially rescue heart defects of Pten deletion mice. We conclude that Akt signaling regulates the cell proliferation of SHF progenitors through coordination of BMP signaling and β-catenin activity.


A comparison of conventional cytology, DNA ploidy analysis, and fluorescence in situ hybridization for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus.
New detection methods with prognostic power are needed for early identification of dysplasia and esophageal adenocarcinoma (EA) in patients with Barrett's esophagus (BE). This study assessed the relative sensitivity and specificity of conventional cytology, DNA ploidy analysis with digital image analysis (DIA), and fluorescence in situ hybridization (FISH) for the detection of dysplasia and adenocarcinoma in endoscopic brushing specimens from 92 patients undergoing endoscopic surveillance for BE. FISH used probes to 8q24 (C-MYC), 9p21 (P16), 17q12 (HER2), and 20q13. Four-quadrant biopsies taken every centimeter throughout visible Barrett's mucosa were used as the gold standard. The sensitivity of cytology, DIA, and FISH for low-grade dysplasia was 5%, 5%, and 50%, respectively; for high-grade dysplasia (HGD), 32%, 45%, and 82%, respectively; and for EA, 45%, 45%, and 100%, respectively. FISH was more sensitive (P < .05) than cytology and DIA for low-grade dysplasia, HGD, and EA. The specificity of cytology, DIA, and FISH among patients (n = 14) with tissue showing only benign squamous mucosa was 93%, 86%, and 100% (P = .22), respectively. All patients with a polysomic FISH result had HGD and/or EA within 6 months (n = 33). There was a significant difference between FISH categories (negative, 9p21 loss, gain of a single locus, and polysomy) for progression to HGD/EA (P < .001). These findings suggest that FISH has high sensitivity for the detection of dysplasia and EA in BE patients, with the power to stratify patients by FISH abnormality for progression to HGD/EA. Additional studies are needed to further evaluate the clinical use of FISH.


Disynaptic inhibition between neocortical pyramidal cells mediated by Martinotti cells.
Reliable activation of inhibitory pathways is essential for maintaining the balance between excitation and inhibition during cortical activity. Little is known, however, about the activation of these pathways at the level of the local neocortical microcircuit. We report a disynaptic inhibitory pathway among neocortical pyramidal cells (PCs). Inhibitory responses were evoked in layer 5 PCs following stimulation of individual neighboring PCs with trains of action potentials. The probability for inhibition between PCs was more than twice that of direct excitation, and inhibitory responses increased as a function of rate and duration of presynaptic discharge. Simultaneous somatic and dendritic recordings indicated that inhibition originated from PC apical and tuft dendrites. Multineuron whole-cell recordings from PCs and interneurons combined with morphological reconstructions revealed the mediating interneurons as Martinotti cells. Martinotti cells received facilitating synapses from PCs and formed reliable inhibitory synapses onto dendrites of neighboring PCs. We describe this feedback pathway and propose it as a central mechanism for regulation of cortical activity.


Parkinson disease survival: a population-based study.
To evaluate whether the survival of patients with Parkinson disease (PD) is shorter than that of the general population. Survival was investigated in a cohort of patients with PD previously identified during a population-based prevalence study (prevalence day, November 1, 1987, reference follow-up date, October 31, 1995). The survival of patients with PD was compared with that of a control sample randomly selected from the same population (2 controls for each case, matched for age, sex, and study municipality). The causes of death in the 2 groups were also compared. Both univariate and multivariate survival analyses were performed to investigate the association with disease-related variables. A door-to-door 2-phase prevalence survey performed in 3 Sicilian municipalities. Fifty-nine patients with PD and 118 controls. Patients with PD showed a high risk of death (relative risk, 2.3; 95% confidence interval, 1.60-3.39). Greater age at November 1, 1987, high Hoehn-Yahr score, and lack of levodopa therapy were associated with a lower survival on univariate analysis. Multivariate analysis confirmed the association between shorter survival among patients with PD and greater age on November 1, 1987. One-way analysis of variance indicated a different effect of levodopa therapy according to age. Multivariate analysis did not confirm this finding. Pneumonia was the cause of death most frequently associated with PD. This study indicates that patients with PD have a shorter survival time than the general population.


Inactivation of Salmonella in organic soil by cinnamaldehyde, eugenol, Ecotrol, and Sporan.
Salmonella can survive in soil for months to years; consequently, soil can be a preharvest source of contamination of produce. Elimination of Salmonella with natural products and processes such as essential oils is important to prevent infection among consumers. Essential oils (distilled extract from plants) have been mainly evaluated in liquid medium and foods in which minimum inhibitory concentration is determined. However, there are no reports describing the impact of essential oils in soil, especially organic soil. We evaluated essential oils for controlling Salmonella enterica serovars in organic soil. Two essential oils (cinnamaldehyde and eugenol), two bio-pesticides (Ecotrol and Sporan), and an organic acid (20% acetic acid) at 0.5%, 1.0%, 1.5%, and 2.0% were mixed with organic sandy soil and inoculated with six different serovars of S. enterica separately. Soils were incubated at room temperature, and samples obtained at 1, 7, and 28 days were enumerated to determine survival. The bactericidal effect of cinnamaldehyde was evident at 0.5%, 1.0%, 1.5%, and 2.0% and during all times of incubation. Overall, Salmonella Negev was the most sensitive strain to oils resulting in significant reductions compared with other strains. Increases in oil concentration resulted in further reduction of Salmonella with all oils used in the study. Up to six log reductions in Salmonella serovars Typhimurium, Negev, and Newport were found after 1 day when cinnamaldehyde, Ecotrol, eugenol, Sporan, or acetic acid was used at 2% level. This study shows the potential use of essential oils to effectively reduce Salmonella populations in soil. The significant reduction of Salmonella could greatly reduce potential contamination of fresh organic produce inadvertently contaminated by soil.


Within-host competition can delay evolution of drug resistance in malaria.
In the malaria parasite P. falciparum, drug resistance generally evolves first in low-transmission settings, such as Southeast Asia and South America. Resistance takes noticeably longer to appear in the high-transmission settings of sub-Saharan Africa, although it may spread rapidly thereafter. Here, we test the hypothesis that competitive suppression of drug-resistant parasites by drug-sensitive parasites may inhibit evolution of resistance in high-transmission settings, where mixed-strain infections are common. We employ a cross-scale model, which simulates within-host (infection) dynamics and between-host (transmission) dynamics of sensitive and resistant parasites for a population of humans and mosquitoes. Using this model, we examine the effects of transmission intensity, selection pressure, fitness costs of resistance, and cross-reactivity between strains on the establishment and spread of resistant parasites. We find that resistant parasites, introduced into the population at a low frequency, are more likely to go extinct in high-transmission settings, where drug-sensitive competitors and high levels of acquired immunity reduce the absolute fitness of the resistant parasites. Under strong selection from antimalarial drug use, however, resistance spreads faster in high-transmission settings than low-transmission ones. These contrasting results highlight the distinction between establishment and spread of resistance and suggest that the former but not the latter may be inhibited in high-transmission settings. Our results suggest that within-host competition is a key factor shaping the evolution of drug resistance in P. falciparum.


Barriers and facilitators of colon cancer screening among patients at faith-based neighborhood health centers.
We determined the barriers to and facilitators of colorectal cancer (CRC) screening among two faith-based, inner city neighborhood health centers in Southwestern Pennsylvania. Data from a random sample of patients 50 years and older (n = 375) were used to estimate logistic regression equations to compare and contrast the predictors of four different CRC screening protocols: (1) fecal occult blood test (FOBT) < or = 2 years ago, (2) colonoscopy < or = 10 years ago, (3) lower endoscopy (colonoscopy or sigmoidoscopy) < or = 10 years ago, and (4) any of these screening measures. Racial differences (between African Americans or Caucasians) in type of colon cancer screening were not found. Controlling for covariates, logistic regression equations showed that a physician's support of colon cancer screening was positively associated with the receipt of colonoscopy (OR: 19.47, 95% CI: 5.45-69.54), lower endoscopy (OR: 10.96, 95% CI: 3.77-31.88) and any colon cancer screening (OR: 10.12, 95% CI: 3.36-30.46). Patients who see their physicians more frequently were also more likely to be screened for CRC. Unlike other studies, the faith-based environment in which these patients are treated may explain the lack of racial disparity specific to our measures of CRC screening.


A Layer-by-Layer Approach To Retain a Fluorescent Glucose Sensing Assay within the Cavity of a Hydrogel Membrane.
A continuous glucose monitoring device that resides fully in the subcutaneous tissue has the potential to greatly improve the management of diabetes. Toward this goal, we have developed a competitive binding glucose sensing assay based on fluorescently labeled PEGylated concanavalin-A (PEGylated-TRITC-ConA) and mannotetraose (APTS-MT). In the present work, we sought to contain this assay within the hollow central cavity of a cylindrical hydrogel membrane, permitting eventual subcutaneous implantation and optical probing through the skin. A "self-cleaning" hydrogel was utilized because of its ability to cyclically deswell/reswell in vivo, which is expected to reduce biofouling and therefore extend the sensor lifetime. Thus, we prepared a hollow, cylindrical hydrogel based on a thermoresponsive electrostatic double network design composed of N-isopropylacrylamide and 2-acrylamido-2-methylpropanesulfonic acid. Next, a layer-by-layer (LbL) coating was applied to the inner wall of the central cavity of the cylindrical membrane. It consisted of 5, 10, 15, 30, or 40 alternating bilayers of positively charged poly(diallyldimethylammonium chloride) and negatively charged poly(sodium 4-styrenesulfonate). With 30 bilayers, the leaching of the smaller-sized component of the assay (APTS-MT) from the membrane cavity was substantially reduced. Moreover, this LbL coating maintained glucose diffusion across the hydrogel membrane. In terms of sensor functionality, the assay housed in the hydrogel membrane cavity tracked changes in glucose concentration (0 to 600 mg/dL) with a mean absolute relative difference of ∼11%.


Travel behavior of low income older adults and implementation of an accessibility calculator.
Given the aging demographic landscape, the concept of walkable neighborhoods has emerged as a topic of interest, especially during the last decade. However, we know very little about whether walkable neighborhoods promote walking among older adults, particularly those with lower incomes. Therefore in this paper we: (i) examine the relation between trip distance and sociodemographic attributes and accessibility features of lower income older adults in Metro Vancouver; and, (ii) implement a web-based application to calculate the accessibility of lower income older adults in Metro Vancouver based on their travel behavior. We use multilevel linear regression to estimate the determinants of trip length. We find that in this population distance traveled is associated with gender, living arrangements, and dog ownership. Furthermore, significant geographical variations (measured using a trend surface) were also found. To better visualize the impact of travel behavior on accessibility by personal profile and location, we also implemented a web-based calculator that generates an Accessibility (A)-score using Google Maps API v3 that can be used to evaluate the accessibility of neighborhoods from the perspective of older adults.


Adipocyte development in primary rat cell cultures, effect of cell density and serum source.
The development of adipocytes was studied in primary cultures of rat adipose tissue stromal-vascular cells on collagen-coated glass coverslips. The effects of cell density and serum source on lipoprotein lipase (LPL), esterase and lipid histochemistry were evaluated. With a mixture of fetal calf serum (FCS; 2%), horse serum (2%) and pig serum (PS; 10%), large and loosely arranged clusters of adipocytes developed with time through an increase in cell number and size. An inverse relationship was observed between cell size and the number of adipocytes in a cluster. Lower cell densities were associated with large cells and the densest areas contained smaller cells. Unilocular adipocytes were observed by d 13 after plating and were generally absent from the densest area of the coverslips. Histochemically detectable LPL activity was demonstrable before lipid deposition in adipocyte clusters. A comparison of FCS (10%) and PS (10%) as the only serum sources indicated higher level of adipocyte esterase activity and lipid deposition in PS cultures. Cultures of cells from weanling (21 to 28 d old) and old (18 mo) rats were similar, whereas cells from younger rats (2 to 4 d old) formed denser cultures that contained fewer adipocytes. These adipocytes were small (less than 30 micron) and morphologically homogeneous (all multilocular). When cells from the very young rats (2 to 4 d old) were plated at low densities, an inverse relationship between cell size and number of cells in a cluster was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)


A temperature sensitive mutant of Saccharomyces cerevisiae defective in pre-rRNA processing.
A recessive temperature sensitive mutant has been isolated that is defective in ribosomal RNA processing. By Northern analysis, this mutant was found to accumulate three novel rRNA species: 23S', 18S' and 7S', each of which contains sequences from the spacer region between 25S and 18S rRNA. 35S pre-rRNA accumulates, while the level of the 20S and 27S rRNA processing intermediates is depressed. Pulse-chase analysis demonstrates that the processing of 35S pre-rRNA is slowed. The defect in the mutant appears to be at the first processing step, which generates 20S and 27S rRNA. 7S' RNA is a form of 5.8S RNA whose 5' end is extended by 149 nucleotides to a position just 5 nucleotides downstream of the normal cleavage site that produces 20S and 27S rRNA. 7S' RNA can assemble into 60S ribosomal subunits, but such subunits are relatively ineffective in joining polyribosomes. A single lesion is responsible for the pre-rRNA processing defect and the temperature sensitivity. The affected gene is designated RRP2.


Expert recommendation: contributions to clinical practice of the new prodrug lisdexamfetamine dimesylate (LDX) in the treatment of attention deficit hyperactivity disorder (ADHD).
Attention deficit hyperactivity disorder (ADHD) is one of the most common neurobiological disorders in childhood, and is characterized by inappropriate levels of inattention, hyperactivity and/or impulsiveness, with an estimated prevalence of 5.29%. ADHD can have a negative impact upon all areas of the life of the patient. The main clinical guides accept multimodal treatment, involving both pharmacological and psychological measures, as the best management approach in ADHD (psychoeducational, behavioural and academic). Lisdexamfetamine dimesylate (LDX) is a new drug for the treatment of ADHD. A multidiscipline expert document has been developed, compiling the scientific evidence referred to this new molecule. The study also addresses the existing shortcomings in current drug therapy for ADHD and the contributions of LDX to routine clinical practice, in an attempt to help and guide physicians in the use of this new treatment. This document is endorsed by the ADHD and Psychoeducational Development task Group of the Spanish Society of Primary Care Pediatrics (Grupo de TDAH y Desarrollo Psicoeducativo de la Asociación Española de Pediatría de Atención Primaria, AEPap), the Spanish Society of Pediatric Neurology (Sociedad Española de Neurología Pediátrica, SENEP) and the Spanish Society of Out-hospital Pediatrics and Primary Care (Sociedad Española de Pediatría Extrahospitalaria y Atención Primaria, SEPEAP).


Understanding barriers and facilitators to implementation of psychosocial care within orthopedic trauma centers: a qualitative study with multidisciplinary stakeholders from geographically diverse settings.
Psychosocial factors are pivotal in recovery after acute orthopedic traumatic injuries. Addressing psychosocial factors is an important opportunity for preventing persistent pain and disability. We aim to identify barriers and facilitators to the implementation of psychosocial care within outpatient orthopedic trauma settings using the Consolidated Framework for Implementation Research (CFIR) and Proctor's taxonomy of implementation outcomes, and to provide implementation strategies derived from qualitative data and supplemented by the Expert Recommendations for Implementing Change. We conducted live video qualitative focus groups, exit interviews and individual interviews with stakeholders within 3 geographically diverse level 1 trauma settings (N = 79; 20 attendings, 28 residents, 10 nurses, 13 medical assistants, 5 physical therapists/social workers, and 3 fellows) at 3 trauma centers in Texas, Kentucky, and Massachusetts. We used directed and conventional content analyses to derive information on barriers, facilitators, and implementation strategies within 26 CFIR constructs nested within 3 relevant Proctor outcomes of acceptability, appropriateness, and feasibility. Stakeholders noted that implementing psychosocial care within their practice can be acceptable, appropriate, and feasible. Many perceived integrated psychosocial care as crucial for preventing persistent pain and reducing provider burden, noting they lack the time and specialized training to address patients' psychosocial needs. Providers suggested strategies for integrating psychosocial care within orthopedic settings, including obtaining buy-in from leadership, providing concise and data-driven education to providers, bypassing stigma, and flexibly adapting to fast-paced clinics. Results provide a blueprint for successful implementation of psychosocial care in orthopedic trauma settings, with important implications for prevention of persistent pain and disability.


Catechol siderophores repress the pyochelin pathway and activate the enterobactin pathway in Pseudomonas aeruginosa: an opportunity for siderophore-antibiotic conjugates development.
Previous studies have suggested that antibiotic vectorization by siderophores (iron chelators produced by bacteria) considerably increases the efficacy of such drugs. The siderophore serves as a vector: when the pathogen tries to take up iron via the siderophore, it also takes up the antibiotic. Catecholates are among the most common iron-chelating compounds used in synthetic siderophore-antibiotic conjugates. Using reverse transcription polymerase chain reaction and proteomic approaches, we showed that the presence of catecholate compounds in the medium of Pseudomonas aeruginosa led to strong activation of the transcription and expression of the outer membrane transporter PfeA, the ferri-enterobactin importer. Iron-55 uptake assays on bacteria with and without PfeA expression confirmed that catechol compounds imported iron into P. aeruginosa cells via PfeA. Uptake rates were between 0.3 × 10(3) and 2 × 10(3) Fe atoms/bacterium/min according to the used catechol siderophore in iron-restricted medium, and remained as high as 0.8 × 10(3) Fe atoms/bacterium/min for enterobactin, even in iron-rich medium. Reverse transcription polymerase chain reaction and proteomic approaches showed that in parallel to this switching on of PfeA expression, a repression of the expression of pyochelin (PCH) pathway genes (PCH being one of the two siderophores produced by P. aeruginosa for iron acquisition) was observed.


The role of some agricultural practices and fertilizer type on both the incidence of stem borers infestation and corn yield in Egypt.
Maize, Zea mays, L. is one of the most important field crops in Egypt. It is used mainly for human, animal and poultry feeding. Corn plants are usually attacked by several injourious insect pests at different stages of development. Out of them, the pink stem borer, Sesamia cretica (Led.), the purple lined borer, Chilo agamemnon (Bles.), and the European corn borer Ostrinia nubilalis (Hb.); which cause great damage and yield losses. It is profitable to adopt an effective and sustainable strategy for controlling these insect-pests. In this concern, sowing dates, planting spaces, foliar fertilizers (macro and micro-nutrients), mineral and/or biofertilization, were investigated to evaluate their role as tools in the so-called Integrated Pest Management (IPM) program of corn pests. In general, the used planting spaces of 60 and 70 cm apart between furrows insignificantly affected the level of stem borers infestation. It was clearly observed that the sowing dates have a role in the incidence of stem borers infestation throughout the corn growing seasons of 1994 and 1995. Moreover, The biofertilized corn plants were more tolerant to the infestation by the stem borers than the minerally fertilized ones. Application of Polytrin significantly decreased the mean numbers of larvae. The tested nutrients preparations affected to less extent, the infestation levels. Concerning the interaction effect of applied nutrients preparations, used sowing dates and/or fertilizer type on the deduced means of larval numbers, it was revealed that: (i) the application of the nutrients preparations decreased to a great extent the effect of the studied sowing dates on the stem borers infestation; particularly in case of spraying ascorbic acid alone or in sequence with Polymex, coppersulphate & Potasin-F, (ii) the dressing of corn grains with the biofertilizers Phosphorin & Rhizobacterin before sowing, lowered to some extent the levels of infestation by Ch. agamemnon and O. nubilalis, in comparison to the minerally fertilized corn plants, especially in case of spraying Potasin-F, copper sulphate and scorbic acid followed by Polymex for Ch. agamemnon. Spraying Ascorbic acid alone or in sequence with Polymex; Potasin-F followed by Copper sulphate gave promising results for the control of O. nubilalis. In comparison to insecticide treatment, the used foliar nutrients & fertilizer type in both sowing dates gave positive interaction effects in decreasing levels of stem borers infestation and greatly improved the yield and yield characteristics of corn plants. Such agricultural practices enabled corn plants to tackle the going on infestation; thus crop loss due to the attack of the stem borers could be compensated.


A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline.
Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia.


Adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of spermatic cord leiomyosarcoma.
The aim of this report is related to adult primary paratesticular mesenchymal tumors with emphasis on a case presentation and discussion of the spermatic cord leiomyosarcoma. Primary paratesticular tumors are rare, only accounting for 7% to 10% of all intrascrotal tumors. In adults, more than 75% of these lesions arise from the spermatic cord, 20% being leiomyosarcoma. Tumor grade, stage, histologic type, and lymph node involvement are independently predictive of prognosis. The case report concerns a 81-year-old man presented with a 3-year history of painless lump in the right hemiscrotum. Scrotal examination demonstrated a 5.1-cm, firm-to-hard mass attached to the spermatic cord. Scrotal ultrasound scan revealed a heterogeneous mass separate from the testis. He was treated with an radical orchi-funicolectomy. Histologically the lesion is composed of spindled cells with often elongated, blunt-ended nuclei and variably eosinophilic cytoplasm. Areas with pleomorphic morphology are present. The level of mitotic activity is equal to 3/10 HPF in the areas with spindle cell morphology and to 12/10 HPF in the areas with pleomorphic morphology. The final diagnosis was that a leiomyosarcoma of the spermatic cord, with grade 1 and grade 2 areas, stage pT2b cN0 and cM0. The patient has been followed up for 3 months with CT scans and shows no signs of recurrence. Spermatic cord leiomyosarcoma, although rare, should be one of the first differential diagnoses for a firm-to-hard lump in the cord. Apart from radical orchi-funicolectomy, there has been added benefit of adjuvant radiotherapy to prevent any loco-regional lymph node recurrence. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1613030331125632.


Viscoelastic properties of bronchial mucus after respiratory physiotherapy in subjects with bronchiectasis.
Previous studies have evaluated the effectiveness of postural drainage (PD), percussion (PERC), the coughing technique (CT), and other types of coughing in subjects with bronchiectasis. However, the application times of these techniques and the quality of the expectorated mucus require further study. The aim of our study was to evaluate the effectiveness of PD, percussion, CT, and huffing in subjects with bronchiectasis and assess the quantity and quality of bronchial mucus produced (measurement of wet and dry weight and determination of viscoelastic properties). Twenty-two subjects with stable bronchiectasis (6 men; mean age: 51.5 y) underwent 4 d of experimental study (CT, PD+CT, PD+PERC+CT, and PD+huffing). The techniques were performed in 3 20-min periods separated by 10 min of rest. Before performing any technique (baseline) and after each period (30, 60, and 90 min), expectorated mucus was collected for analysis of viscoelasticity. A significant increase in the dry weight/wet weight ratio was found after 60 min of PD+PERC+CT (P = .01) and 90 min of PD+huffing (P = .03) and PD+PERC+CT (P = .007) in comparison with CT. PD+PERC+CT and PD+huffing led to the greatest removal of viscoelastic mucus at 60 min (P = .02 and P = .002, respectively) and continued to do so at 90 min (P = .02 and P = .01, respectively) in comparison with CT. An interaction effect was found, as all techniques led to a greater removal of elastic mucus in comparison with CT at 60 min (PD+CT, P = .001; PD+PERC+CT, P < .001; PD+huffing, P < .001), but only PD+PERC+CT and PD+huffing led to a greater removal of elastic mucus than CT at 90 min (P < .001 and P = .005, respectively). PD+PERC+CT and PD+huffing performed similarly regarding the removal of viscoelastic mucus in 2 and 3 20-min periods separated by 10 min of rest. PD+PERC+CT led to the greatest removal of mucus in the shortest period (2 20-min periods separated by 10 min of rest).


Acute and chronic pathological effects of sulfur mustard on genitourinary system and male fertility.
To review the acute and chronic pathological effects of sulfur mustard on the genitourinary system and male fertility. We searched PubMed and Google Scholar to find studies related to the sulfur mustard-induced genitourinary effects and male infertility. Information in the abstracts of non-English related papers as well as those in the proceedings of congresses on sulfur mustard were reviewed as well. In acute phase after sulfur mustard exposure, evidences are in favor of microscopic and macroscopic renal lesions, very low androgen levels, and impaired spermatogenesis. Several years following sulfur mustard exposure, the long-term pathological effects vary from the renal function impairment to the gonadal damage, in particular the spermatogenesis. Nevertheless, carcinogenic effect of sulfur mustard on the genitourinary system as well as the prevalence of male infertility among sulfur mustard-exposed veterans in the chronic post-exposure phase is still unclear. Sulfur mustard causes both acute and chronic injuries to different parts of the genitourinary system.


The cognitive neuroscience of remote episodic, semantic and spatial memory.
The processes and mechanisms implicated in retention and retrieval of memories as they age is an enduring problem in cognitive neuroscience. Research from lesion and functional neuroimaging studies on remote episodic, semantic and spatial memory in humans is crucial for evaluating three theories of hippocampal and/or medial temporal lobe-neocortical interaction in memory retention and retrieval: cognitive map theory, standard consolidation theory and multiple trace theory. Each theory makes different predictions regarding first, the severity and extent of retrograde amnesia following lesions to some or all of the structures mentioned; second, the extent of activation of these structures to retrieval of memory across time; and third, the type of memory being retrieved. Each of these theories has strengths and weaknesses, and there are various unresolved issues. We propose a unified account based on multiple trace theory. This theory states that the hippocampus is needed for re-experiencing detailed episodic and spatial memories no matter how old they are, and that it contributes to the formation and assimilation of semantic memories and schematic spatial maps.


meta -C-H Arylation of Aniline Derivatives via Palladium/ S,O-Ligand/Norbornene Cooperative Catalysis.
Aromatic amines are ubiquitous moieties in organic molecules and their direct functionalization is of great interest in many research areas due to their prevalence in pharmaceuticals and organic electronics. While several synthetic tools exist for the ortho- and para-functionalization of anilines, the functionalization of the less reactive meta-position is not easy to achieve with current methods. To date, the meta-C-H arylation of aniline derivatives has been restricted to either the use of directing groups & templates, or their transformation into anilides & quaternary anilinium salts. Herein, we report the first general and efficient meta-C-H-arylation of non-directed aniline derivatives via cooperative catalysis with a palladium-S,O-ligand-norbornene system. The reaction proceeds under mild conditions with a wide range of aniline derivatives and aryl iodides, while being operationally simple and scalable. Our preliminary mechanistic investigation-including the isolation of several palladium complexes and deuterium experiments-reveal useful insights into the substituent-effects of both the aniline-substrate and the NBE-mediator during the meta-C-H activation step.


Is the aorta truly dextroposed in tetralogy of Fallot? A two-dimensional echocardiographic answer.
The embryogenesis of tetralogy of Fallot is still much debated. In particular, the dextroposition of the aorta is not considered by all pathologists as a genuine abnormality in this congenital heart disease but rather as a false impression due to an exaggeration of the normal overriding caused by dilatation of the aorta secondary to abnormal hemodynamics. We used two-dimensional echocardiography to examine the spatial position of the aortic root in 22 patients with tetralogy of Fallot (aged 5 days to 24 years, mean 6.4 years) and in 23 normal subjects (aged 1 month to 27 years, mean 7.6 years). Using the parasternal short-axis view, we determined the percent rightward displacement of the aortic root in relation to the plane of the atrial septum, and the relationship between the aortic cusps and the atrial septum. We measured the value of the angle luminal diameter, which was defined as the angle between the plane of the atrial septum and the plane of the left coronary-noncoronary commissure and leaflet appositional plane. In the control group, the aortic root was displaced to the right by only 23.6 +/- 7.6%; the atrial septum crossed the posterior aspect of the aortic root at the middle (n = 19) or at the right half of the posterior cusp (n = 4), and the angle luminal diameter had a value of 43.3 +/- 8.8 degrees. In the 22 patients with tetralogy, the percent rightward shift of the aortic root was augmented to 55.5 +/- 9% (p less than .001) and the atrial septum was related to the posterior commissure in 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS)


The complete mitochondrial genome sequence of the indigenous I pig (Sus scrofa) in Vietnam.
The I pig is a long nurtured longstanding breed in Vietnam, and contains excellent indigenous genetic resources. However, after 1970s, I pig breeds have become a small population because of decreasing farming areas and increasing pressure from foreign breeds with a high growth rate. Thus, there is now the risk of the disappearance of the I pigs breed. The aim of this study was to focus on classifying and identifying the I pig genetic origin and supplying molecular makers for conservation activities. This study sequenced the complete mitochondrial genome and used the sequencing result to analyze the phylogenetic relationship of I pig with Asian and European domestic pigs and wild boars. The full sequence was annotated and predicted the secondary tRNA. The total length of I pig mitochondrial genome (accession number KX094894) was 16,731 base pairs, comprised two rRNA (12S and 16S), 22 tRNA and 13 mRNA genes. The annotation structures were not different from other pig breeds. Some component indexes as AT content, GC, and AT skew were counted, in which AT content (60.09%) was smaller than other pigs. We built the phylogenetic trees from full sequence and D loop sequence using Bayesian method. The result showed that I pig, Banna mini, wild boar (WB) Vietnam and WB Hainan or WB Korea, WB Japan were a cluster. They were a group within the Asian clade distinct from Chinese pigs and other Asian breeds in both phylogenetic trees (0.0004 and 0.0057, respectively). These results were similar to previous phylogenic study in Vietnamese pig and showed the genetic distinctness of I pig with other Asian domestic pigs.


Postoperative nomogram for the prediction of disease-free survival in lymph node-negative stage I-IIA cervical cancer patients treated with radical hysterectomy.
The purpose of this study was to develop and validate a nomogram for individual prediction of recurrence and disease-free survival (DFS) among lymph node (LN)-negative early-stage (I-IIA) cervical cancer (CC) patients treated with Type B or Type C2 hysterectomy. Data were collected from patients diagnosed with CC between 1995 and 2017 at the Gynecological Oncology Department, Tepecik Training and Research Hospital. A total of 194 cases with stage IA2-IIA CC were evaluated retrospectively. Patients with stage IA2-IIA CC who underwent radical (Type C2) or modified radical (Type B) hysterectomy and pelvic ± paraaortic LN dissection with LN negativity were included in the study. The relationships between prognostic factors such as stage, tumour size, parametrial involvement, vaginal cuff margin, endomyometrial infiltration, and lymphovascular space invasion status and DFS were compared using a univariable Cox regression model. When the nomogram was prepared, the scores of the risk factors were collected, and we observed that scores were at least 0 to a maximum of 414 points. The concordance-index for the nomogram was 0.895 (95% confidence interval, 0.79-0.99). The nomogram based on the indicated prognostic factors yielded excellent results in predicting recurrence in early-stage CC patients without LN metastasis who underwent radical hysterectomy.Impact statementWhat is already known on this subject? Pathology of radical hysterectomy specimens in patients with early-stage cervical cancer provides information that has predictive prognostic potential. In addition to FIGO stage, other important prognostic factors are lymph node status, tumour size, parametrial involvement, vaginal cuff margin status, endomyometrial infiltration, histological type, patient age, lymphovascular space invasion, histological grade, and depth of cervical stromal invasion.What do the results of this study add? In this study, patients with early-stage cervical cancer who underwent radical and modified radical hysterectomy without retroperitoneal lymph node involvement were evaluated, and recurrence development and factors affecting disease-free survival were investigated. A nomogram consisting of factors influencing disease-free survival was constructed. The total score was determined according to the status of all risk factors. This allowed clear definition of the risk for each patient. A nomogram predicting recurrence in patients with stages IA2-IIA cervical cancer with radical hysterectomy without lymph node involvement has not previously been published.What are the implications of these findings for clinical practice and/or further research? Our study investigated early-stage cervical cancer (CC) patients without lymph node (LN) metastasis. Cox regression analysis was performed with six prognostic factors: FIGO stage, tumour size, parametrial margin infiltration, vaginal cuff margin involvement, endomyometrial infiltration, and LVSI positivity. The nomogram was constructed based on the results of Cox regression. The C-index for the nomogram was 0.895 (95% CI, 0.79-0.99). These results can be considered excellent. The higher concordance index in our study indicates that these six factors may be more valuable in predicting recurrence development in CC patients.


The temporal relationship between alcohol consumption and HIV-medication adherence: a multilevel model of direct and moderating effects.
Previous studies documenting an association between alcohol use and HIV medication nonadherence, have been unable to distinguish between-persons characteristics from within-person characteristics representing the temporally linked effects of alcohol. Hierarchical Linear Modeling (HLM) explored within- and between-person predictors of adherence during the past 14 days, as well as factors that moderate the event-level effects of alcohol consumption among 272 HIV-positive men and women with alcohol problems. On days in which participants drank, they had almost 9 times higher odds of medication nonadherence, with each drink increasing the odds by 20%. The cognitive and alcohol factors had significant between-person effects on adherence. Individuals with strong and rigid beliefs about the importance of strict medication adherence were significantly more affected by each dose of alcohol, while individuals with more alcohol use and problems were less affected by each drink. Regimen complexity increased the effects of having 1 or more drinks. These results highlight the importance of promoting medication adherence among alcohol-using adults, especially among patients with complex regimens or with high confidence and positive attitudes toward HIV medication.


Utility of the anesthetic test dose to avoid catastrophic injury during cervical transforaminal epidural injections.
Reports of serious complications from cervical transforaminal epidural corticosteroid injections often consider accidental intra-arterial injection the most likely mechanism of injury. As a result, many physicians have instituted methods to prevent intravascular injections. Routine use of the anesthetic test dose is one such method. The utility of the anesthetic test dose in this function has not been characterized in the current literature. The aim of this study was to determine the utility of injecting an anesthetic test dose before cervical transforaminal epidural corticosteroid injection and estimate the rate of false-negative intravascular contrast injection using live fluoroscopy and digital subtraction angiography (DSA). Two-center retrospective study. A consecutive cohort of men and women, ages of 23 to 83, who underwent cervical transforaminal epidural injection and received the anesthetic test dose after contrast injection was negative for vascular uptake, observed using live fluoroscopy or DSA. Response to the anesthetic test dose was documented in each procedure note and recorded as either positive or negative. Records of three physiatrists at two academic spine centers (Center A and Center B) were reviewed to identify all patients who received a cervical transforaminal epidural injection during the preceding 5 years, resulting in a cohort of consecutively treated patients at each center. Each patient record was reviewed for demographics, indication for injection, procedure level and side, needle gauge, use of DSA, volume and type of anesthetic test dose used, and result of test dose injection. The test dose was considered positive if the following occurred: agitation or other sudden central nervous system change; gross motor deficits and/or paresthesias in the trunk, legs, or contralateral arm; systemic symptoms of anesthetic toxicity including cardiac arrhythmia, perioral numbness, metallic taste, dizziness, and/or ringing in the ear. For analysis, injections were separated into groups to compare results at Center A to Center B and to compare injections that used DSA to those that did not. The incidence of a positive response was calculated as a percentage from the total number of injections in the group. Differences between groups were analyzed for statistical significance using the Fisher exact test. Six hundred seventy-eight injections were included. Of these, 349 were performed at Center A with test doses given after contrast injection under live fluoroscopy. The remaining 329 were performed at Center B, 183 also using live fluoroscopy, and 146 using DSA. The overall incidence of a positive anesthetic test dose was 0.59% (4/678). There was no significant difference between the incidence at each of the two centers (0.86% [3/349] vs. 0.30% [1/329]; p=.63). The overall incidence after live fluoroscopy was 0.75% (4/532) and after DSA was 0% (0/146), but this difference was not statistically significant (p=.58). Positive symptoms elicited by test dose administration included midneck and contralateral arm pain, metallic taste, dizziness, tachycardia, full body paresthesias, auditory changes, slurred speech, and motor ataxia. In all four cases with a positive response, the procedure was immediately terminated, symptoms resolved, and no lasting complications were observed. The routine use of an anesthetic test dose appears to be safe and capable of detecting potentially dangerous intravascular injections undetected by conventional techniques. Positive responses occur in a small portion of those who receive the test dose injection. Further studies are required to determine the optimal dose and concentration of anesthetic to be used and the time required for observation after test dose administration.


Analysis of mitochondrial DNA diversity in the aleuts of the commander islands and its implications for the genetic history of beringia.
The Aleuts are aboriginal inhabitants of the Aleutian archipelago, including Bering and Copper (Medny) Islands of the Commanders, and seem to be the survivors of the inhabitants of the southern belt of the Bering Land Bridge that connected Chukotka/Kamchatka and Alaska during the end of the Ice Age. Thirty mtDNA samples collected in the Commanders, as well as seven mtDNA samples from Sireniki Eskimos in Chukotka who belong to the Beringian-specific subhaplogroup D2, were studied through complete sequencing. This analysis has provided evidence that all 37 of these mtDNAs are closely related, since they share the founding haplotype for subhaplogroup D2. We also demonstrated that, unlike the Eskimos and Na-Dene, the Aleuts of the Commanders were founded by a single lineage of haplogroup D2, which had acquired the novel transversion mutation 8910A. The phylogeny of haplogroup D complete sequences showed that (1) the D2 root sequence type originated among the latest inhabitants of Beringia and (2) the Aleut 8910A sublineage of D2 is a part of larger radiation of rooted D2, which gave rise to D2a (Na-Dene), D2b (Aleut), and D2c (Eskimo) sublineages. The geographic specificity and remarkable intrinsic diversity of D2 lineages support the refugial hypothesis, which assumes that the founding population of Eskimo-Aleut originated in Beringan/southwestern Alaskan refugia during the early postglacial period, rather than having reached the shores of Alaska as the result of recent wave of migration from interior Siberia.


Do platelets have anything to do with diabetic microvascular disease?
It has been postulated that abnormal platelet and endothelial function may contribute to microangiopathy in diabetes mellitus. If this proposal is correct, alterations in platelet and endothelial function should be found before the appearance of vascular disease in insulin-dependent patients and in animal models of diabetes mellitus. This appears to be the case for the following: platelet aggregation, increased platelet production of the proaggregatory prostaglandin metabolite thromboxane, decreased endothelial production of the antiaggregatory prostaglandin prostacyclin, and decreased platelet survival. Insulin therapy will return some of these findings to normal. Platelet-plasma interactions that promote platelet aggregation and increased plasma levels of the platelet-specific protein beta-thromboglobulin have been reported in insulin-dependent diabetic patients who have not manifested vascular complications as well as in those with vascular complications. It has now been demonstrated in animal models that platelet microthrombi are found in small retinal vessels after months of experimental diabetes. Collectively, these findings demonstrate that alterations in platelet and endothelial function that favor thrombosis occur early in the diabetic state and may contribute to microvascular disease. There are several ongoing studies of antiplatelet agents in diabetic vascular disease that will provide clinical evidence bearing on the major postulate. Until these and other studies are completed, the platelet-endothelial story remains an attractive hypothesis in the genesis of diabetic microvascular disease.


Application of Nanosize Zeolite Molecular Sieves for Medical Oxygen Concentration.
The development of a portable oxygen concentrator is of prime significance for patients with respiratory problems. This paper presents a portable concentrator prototype design using the pressure/vacuum swing adsorption (PVSA) cycle with a deep evacuation step (-0.82 barg) instead of desorption with purge flow to simplify the oxygen production process. The output of the oxygen concentrator is a ~90 vol % enriched oxygen stream in a continuous adsorption and desorption cycle (cycle time ~90 s). The size of the adsorption column is 3 cm in diameter and 20 cm in length. A Li⁺ exchanged 13X nanosize zeolite is used as the adsorbent to selectively adsorb nitrogen from air. A dynamic model of the pressure and vacuum swing adsorption units was developed to study the pressurization and depressurization process inside the microporous area of nanosized zeolites. The describing equations were solved using COMSOL Multiphysics Chemical Engineering module. The output flow rate and oxygen concentration results from the simulation model were compared with the experimental data. Velocity and concentration profiles were obtained to study the adsorption process and optimize the operational parameters.


Impaired nitric oxide-mediated flow-induced coronary dilation in hyperhomocysteinemia: morphological and functional evidence for increased peroxynitrite formation.
Hyperhomocysteinemia (HHcy) is a newly recognized risk factor for myocardial infarction, however, the effect of HHcy on endothelium-dependent flow-induced dilation of coronary arteries is not known. Thus, changes in diameter of small intramural coronary arteries (diameter, approximately 145 microm) isolated from control rats and rats with methionine diet-induced HHcy were investigated by videomicroscopy. Increases in intraluminal flow (from 0 to 40 microl/min) elicited dilations of control vessels (maximum, 25 +/- 2 microm), responses that were absent in HHcy arteries. The nitric oxide (NO) synthase inhibitor L-NAME inhibited flow-induced dilation of control coronaries, whereas it had no effect on responses of HHcy arteries. Dilations of control and HHcy arteries to the NO donor sodium nitroprusside were not different. Responses to flow in HHcy coronary arteries were unaffected by administration of L-arginine or the prostaglandin H(2)/thromboxane A(2) receptor antagonist SQ 29,548. However, in the presence of superoxide dismutase (plus catalase) or the superoxide scavenger Tiron increases in flow elicited L-NAME-sensitive dilations of HHcy coronaries (maximum, 18 +/- 5 microm). Also, superoxide dismutase significantly reduced the enhanced superoxide production of HHcy coronaries (measured by the lucigenin chemiluminescence method). Single vessel Western blotting showed an increased tyrosine nitrosation (a stable biomarker of tissue peroxynitrite formation) in HHcy coronaries. Also, extensive prevalence of 3-nitrotyrosine immunoreactivity was observed in HHcy coronaries that was confined primarily to the subendothelial layers of smooth muscle. We propose that in HHcy an increased level of superoxide scavenges NO forming peroxynitrite, which increases protein nitrosation. The reduced bioavailability of NO impairs flow-induced dilations of coronary arteries, which may contribute to the development of coronary atherosclerosis and ischemic heart disease.