Rendezvous procedure, a simultaneous endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy for choledocholithiasis, in a rural surgical program in Northwest Ontario.
Northwest Ontario has a high prevalence of cholelithiasis, at 1.6 times the provincial norm. There is a concomitant 14% rate of choledocholithiasis. Accessing surgical services in the region often requires extensive travel by air. Choledocholithiasis management is typically with a 2-staged approach, an endoscopic retrograde cholangiopancreatography (ERCP) followed several days or weeks later by laparoscopic cholecystectomy (LC). Regional surgeons were concerned about the patient burden of travel and the loss to follow-up inherent in scheduling two independent procedures at separate hospital admissions. They adopted a 1-stage management, called the rendezvous procedure, which describes the simultaneous performance of an ERCP and LC. We accessed Sioux Lookout Meno Ya Win Health Centre hospital data for all patients receiving an ERCP and LC between 1 June 2019 and 1 December 2022. We documented patient demographics, operative outcomes, length of stay and transfer to other facilities. There were 29 rendezvous procedures performed, with successful cannulation of the ampulla of Vater in 27 (93%) cases and stone removal in 23 (79%), with a complication rate of 7%. The operating time averaged 136 min, and two patients required transfer to a tertiary care centre and four were stented locally and required a return trip to Sioux Lookout for repeat ERCP and successful stone removal. The average length of stay was 2.1 ± 1.3 days. Patients who could not access a rendezvous procedure averaged 46.1 ± 78.1 days between procedures. Managing choledocholithiasis with a 1-stage approach was safe and effective and reduced patient travel, time to definitive care and hospital admissions.


Rapid dephosphorylation of microtubule-associated protein 2 in the rat brain hippocampus after pentylenetetrazole-induced seizures.
We have studied the effect of Pentylenetetrazole (PTZ)-induced seizures on the state of phosphorylation of microtubule-associated protein 2 (MAP-2) from rat hippocampus. A method for the in vivo 32P-labeling of hippocampal proteins has been established, consisting of intracerebro-ventricular injection of 32PO4 of high specific activity. The results obtained indicate that PTZ induces a rapid and transient dephosphorylation of high-molecular-mass MAP-2, which is prevented when the N-methyl-D-aspartate receptor antagonist MK-801 is previously administered. Phosphopeptide mapping of 32P-labeled MAP-2 obtained from hippocampi of PTZ-treated rats reveals a pattern of phosphorylation distinct from that obtained from control saline-treated rats or MK-801 plus PTZ treated rats. We discuss the possible implications of N-methyl-D-aspartate-receptor activation and MAP-2 dephosphorylation on the plastic changes induced in rat brain hippocampus after induced epileptiform activity.


Description and molecular phylogeny of Axinella nayaritensis n. sp. (Porifera: Axinellida) from East Pacific and remarks about the polyphyly of the genus Axinella.
Axinella nayaritensis n. sp. is a typical species of the genus Axinella in spiculation (oxeas and styles), skeletal arrangement (axial condensation from which radiate an extra-axial plumoreticulated skeleton), and external form (arborescent). The new species is orange, branching, up to 25 cm in height, and which usually live in soft bottoms. One of the most conspicuous characteristic of the new species is its aquiferous system, which is formed by a system of superficial canals and meandering ridges which run around the entire length of the branches. The species is compared with Axinella polycapella from Gulf of Mexico, which is very close in morphology, and which it shares a high similarity in the 18S ribosomal RNA region. It was also compared with Axinella aruensis, a very different species from a morphological point of view, which is distributed throughout the northern Australia, Indonesia and Papua New Guinea as both species share a high similarity in the COI mitochondrial gene region. The new species was included in the clade named Axinella by Gazave et al. (2010) for 18S and COI, where also are included eight Axinella-species. Species in this clade are typically arborescent with a choanosomal skeleton differentiated between axial and extra-axial regions. Axinella nayaritensis n. sp. constitute the first record of an Axinella for the east Pacific coast.


Occupational exposure to organic solvents during bridge painting.
Exposure to volatile organic compounds (VOCs) from bridge painting was measured in New York City and New Jersey during the summer and fall seasons from 2005 to 2007. The effect of painting activities (paint coating layer, confinement setup, and application method) and meteorological conditions (temperature, humidity, and wind speed) on solvent exposure to aromatic, ketone, ester, and alkane compounds were individually evaluated. Mixed-effect models were used to examine the combination effects of these factors on the air concentration of total VOCs as the individual compound groups were not present in all samples. Air concentration associated with spraying was not affected by meteorological conditions since spraying was done in a confined space, thus reducing their impact on solvent air concentration. The mixed models for brushing and rolling samples included two fixed factors, i.e. application method and temperature, and one random factor, i.e. sampling day. An independent dataset (daily air samples) was used to validate the mixed model constructed for brushing and rolling samples. The regression line of the predicted values and actual measurements had a slope of 1.32 +/- 0.15 for daily brushing and rolling samples, with almost all points being within the 95% confidence bands. The constructed model provides practical approaches for estimating the solvent exposure from brushing and rolling activities among construction painters. An adjusted mean air concentration derived from the activity-specific spray samples was the best estimate for that painting application.


A 9-year-old-girl with Phelan McDermid Syndrome, who had been diagnosed with an autism spectrum disorder.
Phelan McDermid Syndrome (PHMDS) (OMIM #606232), is a contiguous gene disorder resulting from deletion of the distal long arm of chromosome 22. The 22q13.3 deletions and mutations that lead to a loss of a functional copy of SHANK3 (OMIM *606230) cause the syndrome, characterized by moderate to profound intellectual disability, severely delayed or absent speech, hypotonia, and autism spectrum disorder (ASD) or ASD traits. In this study, we present the case of a 9-year-old girl who had earlier been diagnosed with an ASD. Our findings were a clinically mild intellectual disability, rounded face, pointed chin but no autistic findings. We learned that her neuromotor development was delayed and she had neonatal hypotonia in her history. A heterozygous deletion of MLC1, SBF1, MAPK8IP2, ARSA, SHANK3 and ACR genes, located on 22q13.33, was defined by multiplex ligation-dependent probe amplification (MLPA). Deletion of 22q13.3 (ARSA) region was confirmed by a fluorescent in situ hybridization (FISH) technique. The 22q13.3 deletion was found to be de novo in our patient, and she was diagnosed with PHMDS. We confirmed the 22q13.3 deletion and also determined a gain of 8p23.3-23.2 by array comparative genomic hybridization (aCGH). Fluorescent in situ hybridization was performed to determine whether the deletion was of parental origin and to identify regions of chromosomes where the extra 8p may have been located. The parents were found to be normal. The extra copy of 8p was observed on 22q in the patient. She is the first case reported in association with the 22q deletion of 8p duplications in the literature.


[Limitations of neurologic intensive care].
The indication for intensive care in incurable neurological diseases is discussed. An attempt is made to analyse the problem by presenting two cases of multiple sclerosis and two other cases of amyotrophic lateral sclerosis. There is a clear indication for intensive-care treatment in all cases with life-threatening symptoms and complications, provided there seems to be a chance of reversibility in spite of an eventually poor prognosis. If there is no chance of improvement, and the illness has reached its terminal stage, we do not think, that intensive care is of any benefit for the patient. However, we are not able to make a decision should he insist on such a treatment. When the patient is doomed to die in any case, there is no obligation to inform him about a life-prolonging treatment which is not indicated.


[Relation between dopamine secretion and saltsensitivity in essential hypertension].
The study was designed to explore the mechanism of dopamine secretion related to blood pressure in patients with essential hypertension. The 19 patients with essential hypertension were administered to first 153 mEq of sodium and 70 mEq of potassium diet, next 51 mEq of sodium and finally 340 mEq of sodium for every one week. The patients whose mean blood pressure elevated 10 mmHg or more on the high-sodium loading and depleted 10 mmHg or more on the low-sodium loading were classified as A-, and depleted 10 mmHg or more on the high-sodium loading and elevated 10 mmHg or more on the low-sodium loading as B- and the other patients as C-group. The hypertensive patients were also classified to low- (below 1.0 ng/ml/h), normal- (from 1.0 to 6.0 ng/ml/h) and high- (above 6.0 ng/ml/h) renin groups from the results of plasma renin activity (PRA) obtained after an intravenous injection of furosemide (1 mg/kg) followed by 2-hour ambulation. PRA, plasma aldosterone concentration (PAC), plasma epinephrine concentration (PE), plasma norepinephrine concentration (PNE), plasma dopamine concentration (PDC), circulating plasma volume, body weight, hematocrit and pulse rate were measured at 8 a.m. after sodium loading for 8-days. The patients with essential hypertension were classified into 6 of A- and 2 of B- and 11 of C-groups with the maneuver of sodium loading. The A-group contained 5 patients with low-renin. The circulating plasma volume was relatively large (44.7 +/- 4.8 ml/kg) and markedly increased on the high-sodium loading in 6 patients of A-group. The increment of body weight was higher in A-group than the other groups on the high-sodium loading. In the 2 patients of B-group, hematocrit and pulse rate increased on the low-sodium and decreased on the high-sodium loading, and the variability were larger than the other groups. In the A-group, PRA was significantly low (0.5 +/- 0.4 ng/ml/h) and increased on the low-sodium loading and decreased on the high-sodium loading, and the variability of PRA was lesser than the other groups. In the A-group, PAC was within normal range (5.4 +/- 2.8 ng/dl) and the variation of PAC paralleled with the change of PRA, but the variability of PAC was remarkably low. PE and PNE were unchanged in the A- and the C-groups, but the significant high values were observed in the B-group on the high-sodium loading.


Accreditation. Chassin and Joint Commission aim to inspire. Interview by Howard Larkin.
After two years at the helm of the Joint Commission, Mark Chassin, M.D., is pressing forward with efforts to turn the Joint Commission into a partner with hospitals and other providers and transform health care into a "high reliability" enterprise along the lines of the aviation and nuclear energy industries. Hospitals & Health Networks asked health care experts and Chassin himself how he's doing so far.


[Blood pressure control in hypertensive patients with stable coronary heart disease].
To evaluate systolic blood pressure (SBP) control in hypertensive patients with a stable coronary heart disease (CHD) in general practice in France. A survey was conducted in a sample of 206 general practitionners (GP) representative of the French medical population, in 2003 [LHYCORNE survey]. Each GP had to include 3 hypertensive patients, >18 years old, BP > or = 140/90 mmHg and/or treated for hypertension, and with evidence of CHD documented by myocardial infarction (MI) or angina pectoris (AP) [diagnosis previously established by a cardiologist]. Three office BP measurements were performed, the last two recorded. BP levels were considered as controlled by treatement if they were < 140/90 mmHg. 595 patients were included, 75% men mean age 66 years, 25% women mean age 73 years. All patients had a CHD: MI 46%, AP 54%; 533 (90%) had more than 2 cardiovascular risk factors: hyperlipidemia (411; 69%), smokers (375; 63%), diabetes (158; 27%). Mean BP was 140.7 +/- 14/80.8 +/- 9.7 mmHg; 553 (93%) of these hypertensive patients were treated, and 239 (40%) were considered as having a controlled SBP at the treshold of 140 mmHg: 47% in patients with previous MI and 38% with AP (p < 0.001). Diastolic BP (DBP) was <90 mmHg in 480 (81%) and pulse pressure was >65 mmHg in 202 (34%); 313 (53%) patients received a combination of three drugs or more; 354 (60%) had a beta-blocker, 260 (44%) a calcium channel blocker, 237 (40%) an ACE inhibitor, 287 (48%) other antihypertensive drugs (246 diuretics, 41%); 502 (84%) received antiplatelet therapy, 403 (68%) statins. This survey shows that systolic BP is not at goal in 6/10 hypertensive patients with stable CHD suggesting there is a place for a more effective combination therapy according to evidence-based medicine.


Fabrication of one dimensional polyaniline nanofibers by UV-assisted polymerization in the aqueous phase.
At the room temperature, a novel and environmental friendly approach for synthesizing polyaniline (PANI) nanofibers on a large scale is presented firstly in the aqueous phase by ultraviolet (UV)-assisted polymerization using cetyltrimethylammonium bromide (CTAB) as the "soft-template." It is obvious that the polymerization process can be accelerated under the illumination of UV light and the preliminary mechanism has been pointed out. Furthermore, it also can be noted that the lower concentrations of CTAB and HCl are helpful for the fabrication of smooth and uniform PANI nanofibers. As observed with FE-SEM and TEM, the as-synthesized PANI nanostructures under the appropriate conditions are composed of uniform nanofibers with the average diameter of about 100 nm and the length of several micrometers. Subsequently, the synthesized PANI nanostructures are characterized with UV-vis, FT-IR, XRD spectra, and the typical physical and chemical properties of PANI are displayed. In addition, the conductivity of the synthesized PANI nanofibers was also measured with the four probe method and the excellent conductivity was presented. In summary, the procedure presented here only involving exposure of an acidic aqueous solution of aniline to UV light illumination is so simple and the needed equipment is so low cost, from the viewpoint of technological applications, that the large-scale UV-assisted polymerization of PANI nanofibers from the monomer solution is feasible and promising.


Wnt signaling pathway in retinal vascularization.
Wnt-signaling, a ubiquitous pathway that directs differentiation, cell polarity, and tissue specificity, has been implicated as an important gene-expression pathway in retinal development. An increasing body of evidence supports the importance of Wnt-signaling, and specifically, norrin-mediated Wnt-signaling in retinal development and retinal maintenance. Gene mutations affecting the Wnt-signaling pathways result in a variety of inherited vitreoretinopathies. Additionally, there is growing evidence that prematurity and associated retinopathy are associated with alterations in the Wnt-signaling pathways. Further investigations may allow for improved diagnoses, management, and therapies in the future.


[Maybe it hurts more than we think! Neonatal pain].
Neonatal pain is often undertreated. This is based on the assumption that because of the immature nervous system and the lack of the myelinisation preterm and newborn does not feel pain. It is confirmed by a number of articles that the fetus and neonate can experience and respond to painful events. This publication gives a brief overview of the ontogeny of the pain, short- and long-term postnatal consequences, as well as the perception of the possibility of a particularly frail child population: premature infants and neonates, based on animal and human studies.


Use of iodized salt in processed Philippine food products.
The effects of iodized salt use on the quality of processed Philippine food products were evaluated. Samples for the study included dried-salted and smoked fish products, nitrite-cured pork, and fermented plain and flavored shrimp pastes. Generally, no significant differences were detected between the physicochemical, microbiological and sensory characteristics of the test products prepared with iodized and unfortified NaCl salts. The salting process in each food operation significantly increased the iodine content of the test products. However, subsequent losses in the absorbed iodine were recorded due to the boiling, smoking, drying, fermenting and heating processes in the different operations. It was recommended that studies be undertaken on the addition of iodine to semi-processed or completely processed food products to lessen iodine losses.


Types of pregnancy loss in recurrent miscarriage: implications for research and clinical practice.
In recurrent pregnancy loss, there is much debate about cause and association, as exact pathophysiological mechanisms have not been elucidated. The aim of this study was to assess whether recurrent pregnancy loss (RPL) patterns differ according to causal/associated conditions, suggesting differing disease processes. Following investigation, 427 women with RPL were classified into the following 'diagnostic' groups: idiopathic, oligomenorrhoea, antiphospholipid syndrome (APS) and 'possible' APS. A total of 323 subsequently conceived, and underwent serial ultrasonography in early pregnancy; of these, 87 (26.9%) miscarried, and the types of pregnancy loss for the four diagnostic groups were allocated to either embryo loss (fetal heart never seen) and fetal loss (fetal heart seen prior to pregnancy loss). Overall, there were 75 embryonic losses and 12 fetal losses. The fetal loss rates in each group were similar: idiopathic 5.1%, oligomenorrhoea 3.4%, 'possible' APS 4.9% and APS 4.8%. Serial ultrasound helps to discriminate type of pregnancy loss and demonstrates that embryo loss is more common than fetal loss. More importantly, pregnancy loss patterns do not seem to differ between diagnostic groups in a treated population. The fetal loss rate in each of the diagnostic groups is similar to that in other reported populations.


Recruitment of CRABS CLAW to promote nectary development within the eudicot clade.
Nectaries are secretory organs that are widely present in flowering plants that function to attract floral pollinators. Owing to diversity in nectary positions and structures, they are thought to have originated multiple times during angiosperm evolution, with their potential contribution to the diversification of flowering plants and pollinating animals being considerable. We investigated the genetic basis of diverse nectary forms in eudicot angiosperm species using CRABS CLAW (CRC), a gene required for nectaries in Arabidopsis. CRC expression is conserved in morphologically different nectaries from several core eudicot species and is required for nectary development in both rosids and asterids, two major phylogenetic lineages of eudicots. However, in a basal eudicot species, no evidence of CRC expression in nectaries was found. Considering the phylogenetic distribution of nectary positions and CRC expression analyses in eudicots, we propose that diverse nectaries in core eudicots share conserved CRC gene regulation, and that derived nectary positions in eudicots have altered regulation of CRC. As the ancestral function of CRC lies in the regulation of carpel development, it may have been co-opted as a regulator of nectary development within the eudicots, concomitant with the association of nectaries with reproductive organs in derived lineages.


[Planned non-hospital births in industrialized countries: bureaucratic dream vs. professional responsibility].
This article addresses in how far planned non-hospital births should be an alternative to planned hospital births. Advocates of planned non-hospital deliveries have emphasised patient safety, patient satisfaction, cost effectiveness, and respect for women's rights. We provide a critical evaluation of each of these claims and have doubts that the information available for the pregnant women and the public is in accord with professional responsibility. We understand that the increasing rates of interventions and operative deliveries in hospital births demand an answer, but we doubt that planned home birth is the appropriate professional solution. Complications during non-hospital births inevitably demand a transport of mother and child to a perinatal centre. The time delay by itself is an unnecessary risk for both and this cannot be abolished by bureaucratic quality criteria as introduced for non-hospital births in Germany. Evidence-based studies have shown that modern knowledge of the course of delivery including ultrasound as well as intensive care during the delivery all reduce the rate of operative deliveries. Unfortunately, this is not well-known and only rarely considered during any delivery. All these facts, however, are the best arguments to find a cooperative model within perinatal centres to combine the art of midwifery with modern science, reduction of pain and perinatal care of the pregnant women before, during and after birth. We therefore call on obstetricians, midwifes and health-care providers as well as health politicians to carefully analyse the studies from Western countries showing increasing risks if the model of intention-to-treat is considered and accoordingly not to support planned non-hospital births nor to include these models into prospective trials. Alternatively, we recommend the introduction of a home-like climate within hospitals and perinatal centres, to avoid unnecessary invasive measures and to really care for the pregnant mother before, during and after delivery within a cooperative model without the lack of patient safety for both mother and child in case of impending or acute emergencies.


Long-Term Results after Intraocular Surgery in Treated Retinoblastoma Eyes.
Introduction: The aim of the study was to analyze the results of intraocular surgery in treated retinoblastoma eyes and to assess the long-term results with a priority on local recurrences, secondary enucleation, and metastases. Methods: Retrospective noncomparative case series. Results: From March 1964 to January 2020, 42 eyes of 40 retinoblastoma patients underwent intraocular surgery. Time interval between the last therapy and surgery was 9.5 years (mean: 114 months; median: 54.5 months). 31 eyes were treated for radiogenic cataract formation with a gain in visual acuity of 61.3%. One child developed an upper eyelid metastasis, 3 showed second primary malignancies (SPM), one a late recurrence, and 2 eyes were enucleated. Retinal surgery was performed in 17 eyes; 6 eyes were done as a combined procedure. Indications were radiogenic complications in the sense of a vitreous hemorrhage in 11 eyes and a rhegmatogenous retinal detachment in 6 eyes. 41.2% of the treated eyes had a postoperative gain in visual acuity, whereas 9.5% of the eyes could not be preserved in the long term. Regarding systemic involvement 2 patients developed late recurrences and one a SPM. Conclusion: Surgical therapy in treated retinoblastoma is necessary in isolated cases. In our series, cataract surgery was a safe procedure with a good option of a significant increase in visual acuity. As expected, vitreoretinal treated eyes showed a limited gain in visual acuity, a higher risk of late recurrences, and a lower globe retention rate. Therefore, a careful indication and individual risk-benefit analysis are mandatory.


Fluoroethylnormemantine (FENM) shows synergistic protection in combination with a sigma-1 receptor agonist in a mouse model of Alzheimer's disease.
Fluoroethylnormemantine (FENM) is a Memantine derivative with anti-amnesic and neuroprotective activities showed in the Aβ25-35 pharmacological mouse model of Alzheimer's disease (AD). As AD is a complex multi-factorial neurodegenerative pathology, combination therapies relying on drugs acting through different pathways, have been suggested to more adequately address neuroprotection. As several agonists of the sigma-1 receptor (S1R), an intracellular chaperone, are presently in phase 2 or 3 clinical trials in neurodegenetrative diseases including AD, we examined the potentialities of S1R drug-based combinations with FENM, or Memantine. Aβ25-35-treated mice were treated with S1R agonists (PRE-084, Igmesine, Cutamesine) and/or FENM, or Memantine, during 7 days after intracerebroventricular administration of oligomerized Aβ25-35. Mice were then tested for spatial short-term memory on day 8 and non-spatial long-term memory on days 9-10, using the spontaneous alternation or passive avoidance tests, respectively. The FENM or Memantine combination with Donepezil, that non-selectively inhibits acetylcholinesterase and activates S1R, was also tested. The efficacy of combinations using maximal non-active or minimal active doses of S1R agonist or FENM was analyzed using calculations of the combination index, based on simple isobologram representation. Data showed that most of the FENM-based combinations led to synergistic protection against Aβ25-35-induced learning deficits, for both long- and short-term memory responses, with a higher efficiency on the latter. Memantine led to synergistic combination in short-term memory but poorly in long-term memory responses, with either PRE-084 or Donepezil. These study showed that drug combinations based on FENM and S1R agonists may lead to highly effective and synergistic protection in AD, particularly on short-term memory.


Purkinje cell loss in the cerebellar flocculus in patients with ataxia with ocular motor apraxia type 1/early-onset ataxia with ocular motor apraxia and hypoalbuminemia.
We genetically screened patients with ataxia with ocular motor apraxia type 1 (AOA1)/early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), with a Japanese variant form of Friedreich's ataxia. Three patients were found to have a homozygous insertion mutation of the aprataxin gene (689insT). An elder sister of a patient in this series died of cerebral hemorrhage at the age of 45, and underwent autopsy. In her cerebellar cortex, the mean density of Purkinje cells in the flocculus had predominantly decreased to 6.7% of normal controls, whereas the Purkinje cells in the other areas of the cerebellar hemisphere had decreased to 78.2%. This suggests that the cerebellar flocculus is the primary affected lesion in AOA1/EAOH, which should be associated with ocular motor apraxia.


Tumor inhibition by titanocene complexes: influence upon two xenografted human lung carcinomas.
The influence of the organometallic complexes titanocene dichloride, titanocene dibromide, titanocene bis(hydrogenmaleinate), and titanocene bis(p-aminothiophenolate) bis(hydrochloride) on the development of a lung adenocarcinoma and a small cell lung carcinoma, both xenografted into athymic mice, was investigated in the present study. The tumors were growing s.c., and the substances administered i.p. as fivefold injections according to a Q2D X 5 (every 2 days X 5) or a Q3D X 5 schedule. In the case of lung adenocarcinoma, titanocene complexes inhibited tumor growth by more than 50% resulting in treated/control values of 20%-50%. The suppression remained stable beyond the end of the treatment period. In the case of small cell lung carcinoma, only those Q2D X 5 schedules, which corresponded to LD10 doses, effected considerable and stable growth inhibition to less than 50% of control values. Titanocene dichloride showed the greatest activity against both human tumors, followed by the p-aminothiophenolate, and hydrogenmaleinate derivatives.


Consumer-driven and commercialised practice in dentistry: an ethical and professional problem?
The rise and persistence of a commercial model of healthcare and the potential shift towards the commodification of dental services, provided to consumers, should provoke thought about the nature and purpose of dentistry and whether this paradigm is cause for concern. Within this article, whether dentistry is a commodity and the legitimacy of dentistry as a business is explored and assessed. Dentistry is perceived to be a commodity, dependent upon the context of how services are to be provided and the interpretation of the patient-professional relationship. Commercially-focused practices threaten the fiduciary nature of the interaction between consumer and provider. The solution to managing commercial elements within dentistry is not through rejection of the new paradigm of the consumer of dental services, but in the rejection of competitive practices, coercive advertising and the erosion of professional values and duty. Consumerism may bring empowerment to those accessing dental services. However, if the patient-practitioner relationship is reduced to a mere transaction in the name of enhanced consumer participation, this empowerment is but a myth.


[Underlying Mechanisms of Methamphetamine-Induced Self-Injurious Behavior and Lethal Effects in Mice].
Relatively high doses of psychostimulants induce neurotoxicity on the dopaminergic system and self-injurious behavior (SIB) in rodents. However the underlying neuronal mechanisms of SIB remains unclear. Dopamine receptor antagonists, N-methyl-D-aspartic acid (NMDA) receptor antagonists, Nitric Oxide Synthase (NOS) inhibitors and free radical scavengers significantly attenuate methamphetamine-induced SIB. These findings indicate that activation of dopamine as well as NMDA receptors followed by radical formation and oxidative stress, especially when mediated by NOS activation, is associated with methamphetamine-induced SIB. On the other hand, an increase in the incidence of polydrug abuse is a major problem worldwide. Coadministered methamphetamine and morphine induced lethality in more than 80% in mice, accompanied by an increase in the number of poly (ADP-ribose) polymerase (PARP)-immunoreactive cells in the heart, kidney and liver. The lethal effect and the increase in the incidence of rupture or PARP-immunoreactive cells induced by the coadministration of methamphetamine and morphine were significantly attenuated by pretreatment with a phospholipase A2 inhibitor or a radical scavenger, or by cooling of body from 30 to 90 min after drug administration. These results suggest that free radicals play an important role in the increased lethality induced by the coadministration of methamphetamine and morphine. Therefore, free radical scavengers and cooling are beneficial for preventing death that is induced by the coadministration of methamphetamine and morphine. These findings may help us better understand for masochistic behavior, which is a clinical phenomenon on SIB, as well as polydrug-abuse-induced acute toxicity.


Surgical management of the tight lip syndrome in the Shar-Pei dog.
The lower lip in some Shar-Pei puppies curls up over the mandible, causing lingual displacement of the incisor and canine teeth and may result in interference with the natural growth of the mandible. Surgical correction of this defect at the proper age can allow the mandible to grow normally and avoid development of an uncomfortable mouth. Two methods of correction are described. Cheiloplasty has been used by the author on 99 puppies over a 10 year period, only two of which were returned for additional surgery because the result was inadequate; the cheiloplasty procedure was repeated in these two dogs. Excision of an elliptical section of the skin of the chin was performed once during the same 10 year period.


Measurement of axial phase difference of density fluctuations owing to spontaneously excited waves by using microwave reflectometer on GAMMA 10/PDX.
In the GAMMA 10/PDX tandem mirror, plasma with strong ion-temperature anisotropy is produced by using the ion cyclotron range of frequency waves. This anisotropy of ion temperature causes several Alfvén-Ion-Cyclotron (AIC) waves to spontaneously excite in the frequency range just below the ion cyclotron frequency. In addition, difference-frequency (DF) waves are excited in the radial inner region of the plasma by wave-wave coupling among the AIC waves. The radial density profiles were measured at multi-axial positions using a frequency-modulation reflectometer with an axial array of microwave antennas, and an axial variation of the density was found to be significant. In addition, a relative phase difference of the DF wave between axially separated two points was first obtained by finely choosing the probing frequency of the reflectometers with a maximum coherence used as a measure, indicating that the DF wave is a propagating wave, while the pump AIC waves are standing waves in the axial region of measurement.


Galectin-3: an early predictive biomarker of modulation of airway remodeling in patients with severe asthma treated with omalizumab for 36 months.
Bronchial asthma is a heterogeneous disease characterized by three cardinal features: chronic inflammation, variable airflow obstruction, and airway hyperresponsiveness. Asthma has traditionally been defined using nonspecific clinical and physiologic variables that encompass multiple phenotypes and are treated with nonspecific anti-inflammatory therapies. Based on the modulation of airway remodeling after 12 months of anti-immunoglobulin E (IgE) treatment, we identified two phenotypes (omalizumab responder, OR; and non-omalizumab responder, NOR) and performed morphometric analysis of bronchial biopsy specimens. We also found that these two phenotypes were correlated with the presence/absence of galectin-3 (Gal-3) at baseline (i.e., before treatment). The aims of the present study were to investigate the histological and molecular effects of long-term treatment (36 months) with anti-IgE and to analyze the behavior of OR and NOR patients. All patients were treated with the monoclonal antibody anti-IgE omalizumab for 36 months. The bronchial biopsy specimens were evaluated using morphometric, eosinophilic, and proteomic analysis (MudPIT). New data were compared with previous data, and unsupervised cluster analysis of protein profiles was performed. After 36 months of treatment with omalizumab, reduction of reticular basement membrane (RBM) thickness was confirmed in OR patients (Gal-3-positive at baseline); similarly, the protein profiles (over 500 proteins identified) revealed that, in the OR group, levels of proteins specifically related to fibrosis and inflammation (e.g., smooth muscle and extracellular matrix proteins (including periostin), Gal-3, and keratins decreased by between 5- and 50-fold. Eosinophil levels were consistent with molecular data and decreased by about tenfold less in ORs and increased by twofold to tenfold more in NORs. This tendency was confirmed (p < 0.05) based on both fold change and DAVE algorithms, thus indicating a clear response to anti-IgE treatment in Gal-3-positive patients. Our results showed that omalizumab can be considered a disease-modifying treatment in OR. The proteomic signatures confirmed the presence of Gal-3 at baseline to be a biomarker of long-term reduction in bronchial RBM thickness, eosinophilic inflammation, and muscular and fibrotic components in omalizumab-treated patients with severe asthma. Our findings suggest a possible relationship between Gal-3 positivity and improved pulmonary function.


Three colorimetric and off-on fluorescent chemosensors for Fe3+ in aqueous media.
Three Rhodamine B derivatives were synthesized and characterized by ESI-MS, NMR, HR-MS and IR. The probes exhibit high selectivity and sensitivity towards Fe(3+) over other metal ions in CH3CN-water. Upon the addition of Fe(3+), the spirocyclic ring of the probe was opened and a significant enhancement of visible color and fluorescence within the range of 540-700 nm was observed. The colorimetric and fluorescent response to Fe(3+) can be conveniently detected even by the naked eye, which provides a facile method for the visual detection of Fe(3+). Job's plot, fluorescence titration and MS indicated the formation of 1:2 complexes between the probes and Fe(3+). The reversibility of the reaction establishes the potential of these probes as chemosensors for Fe(3+) detection.


Intelligibility of sentences recorded from the uterus of a pregnant ewe and from the fetal inner ear.
The intelligibility of sentences recorded from the uterus of a pregnant ewe and from the near-term fetal sheep inner ear was judged by 30 listeners. Sentences were presented to the ewe at 95 and 105 dB SPL while sequential recordings of sound with a hydrophone and a cochlear microphonic (CM) with electrodes were made. Recordings were randomized and presented to listeners to judge the intelligibility of sentences processed through the ewe and fetal inner ear. Intelligibility scores were nearly 99% for air and uterus conditions, dropped to 73% for CM ex utero and to 41% for CM in utero. Results indicated that filtering provided by the tissues and fluids of the maternal abdomen did not affect sentence intelligibility significantly, but the filtering effects as the signal passed into the fetal inner ear resulted in much poorer intelligibility.


Langevin picture of anomalous diffusion processes in expanding medium.
The expanding medium is very common in many different fields, such as biology and cosmology. It brings a nonnegligible influence on particle's diffusion, which is quite different from the effect of an external force field. The dynamic mechanism of a particle's motion in an expanding medium has only been investigated in the framework of a continuous-time random walk. To focus on more diffusion processes and physical observables, we build the Langevin picture of anomalous diffusion in an expanding medium, and conduct detailed analyses in the framework of the Langevin equation. With the help of a subordinator, both subdiffusion process and superdiffusion process in the expanding medium are discussed. We find that the expanding medium with different changing rate (exponential form and power-law form) leads to quite different diffusion phenomena. The particle's intrinsic diffusion behavior also plays an important role. Our detailed theoretical analyses and simulations present a panoramic view of investigating anomalous diffusion in an expanding medium under the framework of the Langevin equation.


Use of a Garment as an Alternative to Body Painting in Equine Musculoskeletal Anatomy Teaching.
Living anatomy is gaining increasing popularity as an alternative to the use of preserved cadaver specimens in musculoskeletal anatomy teaching. This article describes the development of a garment painted with musculoskeletal structures as an alternative to body painting. Garments offer some advantages over traditional body painting in anatomy teaching. The technique can be used across different disciplines, enhances students' ability to identify anatomic structures in living bodies, and provides insights into the topography of one or more body systems at the same time. The fact that garments are amenable to palpation by large groups of students with no damage to the painting favors repeated use in hands-on wet labs. Garments such as the one described in this article introduce a novel approach to interdisciplinary teaching and learning, which can be combined with traditional anatomy teaching methods. The first garment produced depicts part of the equine musculoskeletal system. Steps in garment construction are highlighted and indications, advantages, and limitations of the method discussed.


[The possibility of modern segregation analysis to discriminate monogenic and multifactorial types of the inheritance of traits. The reliability of models and the power of the analysis].
Using computer simulation of family data sets within segregation analysis limits the comparative research of the autosomal major locus model (MLM) and the multifactorial model (MFM) which described the basic types of inheritance of the alternative traits (affected--nonaffected) has been conducted. Robustness of models (statistical aspect) and the power of the analysis (its possibility to discriminate MLM and MFM) are tested. It is shown that permissible level of relative errors for estimated population's frequency is increased, when the values of parameters of models are increased (with decrease of sporadic cases' portion). The power of the analysis is the greatest in the field of greatest robustness of models: the higher the parameters of models, the portion of sporadic cases being low, the stronger the power of the analysis. MFM satisfactorily describes family distribution given by additive MLM. On the contrary, if the MLM corresponds to the multifactorial traits, this model is additive. It is shown that the possibility of the analysis to reject alternative model is decreased when determination of model grows down.


Fibonacci anyons from Abelian bilayer quantum Hall states.
The possibility of realizing non-Abelian statistics and utilizing it for topological quantum computation (TQC) has generated widespread interest. However, the non-Abelian statistics that can be realized in most accessible proposals is not powerful enough for universal TQC. In this Letter, we consider a simple bilayer fractional quantum Hall system with the 1/3 Laughlin state in each layer. We show that interlayer tunneling can drive a transition to an exotic non-Abelian state that contains the famous "Fibonacci" anyon, whose non-Abelian statistics is powerful enough for universal TQC. Our analysis rests on startling agreements from a variety of distinct methods, including thin torus limits, effective field theories, and coupled wire constructions. We provide evidence that the transition can be continuous, at which point the charge gap remains open while the neutral gap closes. This raises the question of whether these exotic phases may have already been realized at ν=2/3 in bilayers, as past experiments may not have definitively ruled them out.


Airway obstruction and the risk of myocardial infarction and death from coronary heart disease: a national health examination survey with a 33-year follow-up period.
Chronic obstructive pulmonary disease (COPD) has been associated with coronary mortality. Yet, data about the association between COPD and acute myocardial infarction (MI) remain scarce. We aimed to study airway obstruction as a predictor of MI and coronary mortality among 5576 Finnish adults who participated in a national health examination survey between 1978 and 1980. Subjects underwent spirometry, had all necessary data, showed no indications of cardiovascular disease at baseline, and were followed up through record linkage with national registers through 2011. The primary outcome consisted of a major coronary event-that is, hospitalization for MI or coronary death, whichever occurred first. We specified obstruction using the lower limit of normal categorization. Through multivariate analysis adjusted for potential confounding factors for coronary heart disease, hazard ratios (HRs) (with the 95% confidence intervals in parentheses) of a major coronary event, MI, and coronary death reached 1.06 (0.79-1.42), 0.84 (0.54-1.31), and 1.40 (1.04-1.88), respectively, in those with obstruction compared to others. However, in women aged 30-49 obstruction appeared to predict a major coronary event, where the adjusted HR reached 4.21 (1.73-10.28). In conclusion, obstruction appears to predict a major coronary event in younger women only, whereas obstruction closely associates with the risk of coronary death independent of sex and age.


Local-pooled-error test for identifying differentially expressed genes with a small number of replicated microarrays.
In microarray studies gene discovery based on fold-change values is often misleading because error variability for each gene is heterogeneous under different biological conditions and intensity ranges. Several statistical testing methods for differential gene expression have been suggested, but some of these approaches are underpowered and result in high false positive rates because within-gene variance estimates are based on a small number of replicated arrays. We propose to use local-pooled-error (LPE) estimates and robust statistical tests for evaluating significance of each gene's differential expression. Our LPE estimation is based on pooling errors within genes and between replicate arrays for genes in which expression values are similar. We have applied our LPE method to compare gene expression in naïve and activated CD8+ T-cells. Our results show that the LPE method effectively identifies significant differential-expression patterns with a small number of replicated arrays. The methodology is implemented with S-PLUS and R functions available at http://hesweb1.med.virginia.edu/bioinformatics


[The Millennia 2015 Women and eHealth Study 2010-2012: networks and innovative programs].
The Women and eHealth Study 2010-2012 is conducted with the vision to constitute a Millennia 2015 powerful demonstration of women empowerment in the arena of eHealth and telemedicine through digital solidarity and gender equity. The overall objective is to stimulate more women to use advanced technologies combined with innovative integrated collaborative leadership programs. The article describes the study and the subsequent networks WeTelemed and WeObservatory conducted by women in developing countries with the ambition to reach the populations living in isolated communities.


Ultrastructural localization of scrapie prion proteins in cytoplasmic vesicles of infected cultured cells.
Infectious scrapie prions are composed largely, if not entirely, of an abnormal isoform of the prion protein (PrP) designated PrPSc. In scrapie-infected mouse neuroblastoma (ScN2a) and hamster brain (ScHaB) cells, PrPSc accumulates primarily within the cell cytoplasm, whereas cellular PrP (PrPC) is anchored to the external surface of the plasma membrane by a glycoinositol phospholipid moiety. To determine the subcellular localization of PrPSc, scrapie-infected cells were grown to approximately 75% confluency, fixed briefly, and then incubated with guanidine thiocyanate before antibody staining and examination by electron microscopy. PrPSc immunoreactivity was enhanced by denaturation with guanidine isothiocyanate which also permeabilized cells (Taraboulos et al., J Cell Biol 110:2117, 1990). As judged both by deposition of immunoperoxidase reaction product (diaminobenzidine) and by presence of immunogold particles, PrPSc was identified in discrete vesicular foci and some large bodies in the cytoplasm of scrapie-infected cells. Some vesicles with PrPSc staining also contained myelin figures resembling those found in autophagic vacuoles forming secondary lysosomes. The presence of PrPSc in secondary lysosomes is inferred from colocalization of guanidine isothiocyanate enhanced PrP immunoreactivity and acid phosphatase. Neither the diaminobenzidine reaction product nor immunogold particles were observed in association with the nucleus, endoplasmic reticulum, or Golgi stacks. Exposure of scrapie-infected cells to the brefeldin A dispersed the Golgi apparatus but did not alter the morphologic distribution of PrPSc, indicating that no detectable PrPSc was associated with Golgi stacks. It remains to be established whether secondary lysosomes are involved in the post-translational formation of PrPSc.


[Role of medical technologists in the infection control team].
The infection control team (ICT) plays important roles in many different aspects of infection control. They include (1) surveillance for hospital-acquired infection, (2) developing the infection control manual, (3) checking that the manual is followed correctly, (4) giving information about the isolation of microorganisms in the hospital, (5) educating and instructing medical staff, etc. Many data have been accumulated on a database in the microbiology laboratory. Bacterial samples are also examined in the microbiological laboratory therefore medical technologists will be the first to notice hospital-acquired infection. Offering prompt information, obtained by surveillance or routine work, greatly contributes to infection control. Furthermore, a 24hr system for the microbiological laboratory may prevent occupational infection of health care workers. The role of the medical technologist in ICT is thus important. To prevent outbreaks of infection, the regional network is also important for the collection of information about the pathogen and the susceptibility of antimicrobial agents in the region. The medical technologist should participate in and communicate with this network. As mentioned above, the inclusion of medical technologists in infection control practice is essential. To participate in the ICT, medical technologists need to have communication skills, and be recognized by other team members as an essential member.


Clonal variation in Xenorhabdus nematophila virulence and suppression of Manduca sexta immunity.
Virulence of the insect pathogen Xenorhabdus nematophila is attributed in part to its ability to suppress immunity. For example, X. nematophila suppresses transcripts encoding several antimicrobial proteins, even in the presence of Salmonella enterica, an inducer of these transcripts. We show here that virulence and immune suppression phenotypes can be lost in a subpopulation of X. nematophila. Cells that have undergone 'virulence modulation' (vmo) have attenuated virulence and fail to suppress antimicrobial transcript levels, haemocyte aggregation and nodulation in Manduca sexta insects. When plated on certain media, vmo cells have a higher proportion of translucent (versus opaque) colonies compared with non-vmo cells. Like vmo strains, translucent colony isolates are defective in virulence and immune suppression. The X. nematophila genome encodes two 'opacity' genes with similarity to the Ail/PagC/Rck family of outer membrane proteins involved in adherence, invasion and serum resistance. Quantitative polymerase chain reaction analysis shows that RNA levels of one of these opacity genes, opaB, are higher in opaque relative to translucent colonies. We propose that in X. nematophila opaB may be one of several factors involved in immune suppression during infection, and expression of these factors can be co-ordinately eliminated in a subpopulation, possibly through a phase variation mechanism.


High concentrations of N-terminal peptide of type III procollagen in the sera of patients with various cancers, with special reference to liver cancer.
The concentrations of N-terminal peptide of type III procollagen in the sera of patients with various cancers were measured by radioimmunoassay. The mean value (with standard deviation) in the control group was 9.9 +/- 2.6 ng/ml. Serum levels exceeding 15 ng/ml were defined as positive, and it was found that 94% of 18 patients with primary liver cancer with cirrhosis, 88% of 8 patients with primary liver cancer without cirrhosis, 77% of 13 patients with metastatic liver cancer, 86% of 7 patients with recurrent breast cancer, 86% of 8 patients with colonic cancer, 75% of 8 patients with pancreatic cancer, 70% of 23 patients with stomach cancer, 51% of 35 patients with lung cancer, and 54% of 28 patients with uterine cancer showed positive levels. The concentrations showed great intersubject variations, probably reflecting the activity of tumor growth and/or invasion. The concentrations in the sera of patients with primary liver cancer with cirrhosis were generally higher than those in patients with liver cirrhosis alone or primary liver cancer without cirrhosis. This result suggested that the growth of primary liver cancer complicated by cirrhosis might be detected by serial measurements of this peptide in the serum of patients with liver cirrhosis. Present data suggested that this peptide is not cancer-specific, but assay of the peptide might be of value as an auxiliary means of detecting and monitoring various cancers, especially liver cancer.


Identification of allosteric inhibitors of the ecto-5'-nucleotidase (CD73) targeting the dimer interface.
The ecto-5'-nucleotidase CD73 plays an important role in the production of immune-suppressive adenosine in tumor micro-environment, and has become a validated drug target in oncology. Indeed, the anticancer immune response involves extracellular ATP to block cell proliferation through T-cell activation. However, in the tumor micro-environment, two extracellular membrane-bound enzymes (CD39 and CD73) are overexpressed and hydrolyze efficiently ATP into AMP then further into immune-suppressive adenosine. To circumvent the impact of CD73-generated adenosine, we applied an original bioinformatics approach to identify new allosteric inhibitors targeting the dimerization interface of CD73, which should impair the large dynamic motions required for its enzymatic function. Several hit compounds issued from virtual screening campaigns showed a potent inhibition of recombinant CD73 with inhibition constants in the low micromolar range and exhibited a non-competitive inhibition mode. The structure-activity relationships studies indicated that several amino acid residues (D366, H456, K471, Y484 and E543 for polar interactions and G453-454, I455, H456, L475, V542 and G544 for hydrophobic contacts) located at the dimerization interface are involved in the tight binding of hit compounds and likely contributed for their inhibitory activity. Overall, the gathered information will guide the upcoming lead optimization phase that may lead to potent and selective CD73 inhibitors, able to restore the anticancer immune response.


Electron microscopic mapping of secondary structures in bacterial 16S and 23S ribosomal ribonucleic acid and 30S precursor ribosomal ribonucleic acid.
Electron microscopy revealed reproducible secondary structure patterns within partially denatured 16S and 23S ribosomal ribonucleic acid (rRNA) from Escherichia coli. When prepared with 50% formamide-100 mM ammonium acetate, 16S rRNA included two small hairpins that appeared in over 50% of all molecules. Three open loops were observed with frequencies of less than 25%. In contrast, 23S rRNA included a terminal open loop and two additional large structures in over 75% of all molecules. These secondary structure patterns were conserved in the 16S and 23S rRNA from Pseudomonas aeruginosa. The secondary structure of the 30S precursor rRNA from the ribonclease III-deficient E. coli mutant AB105 was mapped after partial denaturation in 70% formamide-100 mM ammonium acetate. Two large open loops were superimposed on the 16S and 23S rRNA secondary structure patterns. These loops were the most frequent structures found on the precursor, and their stems coincided with ribonuclease III cleavage sites. A tentative 5'-3 orientation was determined for the secondary structure patterns of 16S and 23S rRNA from their relative locations within 30S precursor rRNA. The relation of secondary structure to ribosomal protein binding and ribonuclease III cleavage is discussed.


Triangulating abuse liability assessment for flavoured cigar products using physiological, behavioural economic and subjective assessments: a within-subjects clinical laboratory protocol.
In the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability. Participants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18-25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models. The Virginia Commonwealth University Institutional Review Board approved the study (VCU IRB: HM20007848). Dissemination channels for study findings include scientific journals, scientific meetings, and policy briefs. NCT02937051.


Deep Symmetric Adaptation Network for Cross-Modality Medical Image Segmentation.
Unsupervised domain adaptation (UDA) methods have shown their promising performance in the cross-modality medical image segmentation tasks. These typical methods usually utilize a translation network to transform images from the source domain to target domain or train the pixel-level classifier merely using translated source images and original target images. However, when there exists a large domain shift between source and target domains, we argue that this asymmetric structure, to some extent, could not fully eliminate the domain gap. In this paper, we present a novel deep symmetric architecture of UDA for medical image segmentation, which consists of a segmentation sub-network, and two symmetric source and target domain translation sub-networks. To be specific, based on two translation sub-networks, we introduce a bidirectional alignment scheme via a shared encoder and two private decoders to simultaneously align features 1) from source to target domain and 2) from target to source domain, which is able to effectively mitigate the discrepancy between domains. Furthermore, for the segmentation sub-network, we train a pixel-level classifier using not only original target images and translated source images, but also original source images and translated target images, which could sufficiently leverage the semantic information from the images with different styles. Extensive experiments demonstrate that our method has remarkable advantages compared to the state-of-the-art methods in three segmentation tasks, such as cross-modality cardiac, BraTS, and abdominal multi-organ segmentation.


The relevance of the bleeding severity in the treatment of acquired haemophilia - an update of a single-centre experience with 67 patients.
Acquired haemophilia (AH), an autoimmune disorder with clinical features ranging from harmless haematomas to life-threatening bleedings, still has a mortality rate of up to 25%. Owing to its low frequency (1-4 x 10(6)), standardized treatment protocols for its variable manifestations are not available. In case of prominent severe bleedings, the treatment should aim at rapid elimination of the antibody to protect patients from bleedings and on reinduction of long-term immune tolerance. Clinical data, short- and long-term treatment results of 67 patients diagnosed by our centre are presented. Patients were treated depending on their bleeding severity either by an immunosuppressive treatment alone, or in case of life-threatening bleedings, by a combined protocol (modified Bonn-Malmö protocol, MBMP) consisting of antibody depletion through immunoadsorption, intravenous immunoglobulin treatment, immunosuppression and high-dose factor VIII (FVIII) substitution. Mild bleedings occurred in two patients who were treated successfully alone by immunosuppression. Complete remission (CR) was achieved in 90% of the patients treated with MBMP (60). Of the six patients (10%) who achieved a partial remission (PR), four suffered from cancer. Mortality under MBMP was not seen. In contrast, five patients, in whom diagnosis of AH was delayed, experienced fatal outcome during surgical interventions before initiation of MBMP treatment. Prognosis in AH depends mainly on its prompt diagnosis. Treatment procedures should be adapted to bleeding severity and inhibitor titres. Under these conditions, AH is a potentially curable autoimmune disorder with an excellent prognosis.


Carbon monoxide activation via O-bound CO using decamethylscandocinium-hydridoborate ion pairs.
Ion pairs [Cp*(2)Sc](+)[HB(p-C(6)F(4)R)(3)](-) (R = F, 1-F; R = H, 1-H) were prepared and shown to be unreactive toward D(2) and α-olefins, leading to the conclusion that no back-transfer of hydride from boron to scandium occurs. Nevertheless, reaction with CO is observed to yield two products, both ion pairs of the [Cp*(2)Sc](+) cation with formylborate (2-R) and borataepoxide (3-R) counteranions. DFT calculations show that these products arise from the carbonyl adduct of the [Cp*(2)Sc](+) in which the CO is bonded to scandium through the oxygen atom, not the carbon atom. The formylborate 2-R is formed in a two-step process initiated by an abstraction of the hydride by the carbon end of an O-bound CO, which forms an η(2)-formyl intermediate that adds, in a second step, the borane at the carbon. The borataepoxide 3-R is suggested to result from an isomerization of 2-R. This unprecedented reaction represents a new way to activate CO via a reaction channel emanating from the ephemeral isocarbonyl isomer of the CO adduct.


[Studies on immunospecificity of skin test using tumor extract in gynecological malignancy (author's transl)].
Twenty-four patients of cervical cancer and 15 of ovarian cancer were studied to ascertain the presence of tumor-specific immune-response by in vivo and in vitro immunoassays. Soluble extracts of cell membranes as antigens were prepared from surgically obtained tumor tissues and normal tissues by 3M-Kcl method. Skin test and in vitro assays, such as Macrophage Migration Inhibition test, Leucocyte Adherence Inhibition assay and lymphocyte blastogenesis, were performed using these extracted antigens. 1. In skin test with autochthonous tumor extracts, positive reaction was revealed in 12.5% of cervical cancer cases and in 13.3% of ovarian cancer cases. There was no positive reaction in skin test with normal tissue extracts and allogeneic tumor extracts. 2. In in vitro assays, the percentage of positive was 30 to 40% in cervical cancer and 50 to 60% in ovarian cancer. It was observed that the patients with positive skin test tended to show also positive reaction in in vitro assays. 3. The positive percentage of non-specific skin tests (PHA, DNCB, PPD and SK-SD) was higher in the positive cases than in the negative in the tumor-specific skin test. Consequently, it was suggested that there were tumor-specific antigens in tumor tissues of cervical cancer or ovarian cancer and immune response of patients to these antigens might depend on individual-specificity.


[Epstein-Barr virus-related B-cell lymphoma of the skin which developed early after cord blood transplantation for angioimmunoblastic T-cell lymphoma].
We report here a rare case of EBV-related post-transplantation lymphoproliferative disorder (PTLD) localized to the skin. The patient was a 64-year-old man diagnosed with angioimmunoblastic T cell lymphoma (AITL). He underwent cord blood transplantation with a reduced intensity conditioning regimen during partial remission after chemotherapy. On day 70 after transplantation, subcutaneous tumors developed near the left scapula and in the left upper arm. Pathological examination of the skin tumor revealed that this tumor was composed of diffuse large centroblast-like cells, the majority of which were CD20 positive, CD 79a positive, CD30 positive and Epstein-Barr virus (EBV) latency-associated RNA (EBER) positive, and EBV-DNA was also detected in tumor cells. At that time, real-time polymerase chain reaction documented no evidence of the EBV genome in his blood. Chimerism analysis revealed that the tumor cells were derived from donor cells, which led to the diagnosis of EBV-related PTLD. For treatment, in addition to decreasing the dose of tacrolimus, we administered rituximab and local irradiation to skin lesions, which led to disappearance of the tumors followed by continued complete remission.


A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis.
Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS). To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS. A sample of MS patients, 60 relapsing-remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT). The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery. The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.


Evaluation of the specificity of an intradermal test with recombinant tuberculosis allergen in Bacillus Calmette-Guérin-vaccinated healthy volunteers.
The tuberculin skin test has significant limitations for use in individuals vaccinated with BCG. The presence in the genome of Mycobacterium tuberculosis of the RDI region, which is absent in the genome of Mycobacterium bovis BCG and most non-tuberculous mycobacteria, made it possible to develop new skin tests, which include a skin test with a recombinant tuberculosis allergen [RTA (Diaskintest®, JSC Generium, Russia)]. Diaskintest has shown high diagnostic performance in clinical trials and in conditions of high prevalence of tuberculosis infection. In 2021, the Russia was excluded from the WHO list of high TB burden countries, which makes relevant an assessment of the specificity of the RTA test under conditions of low epidemiologic risk for tuberculosis to confirm the high specificity of the test. To assess the specificity of Diaskintest in the regions of the Russian Federation with low epidemiologic risk for tuberculosis. A multicenter, open-label, prospective study was conducted, which included 150 healthy volunteers aged 18-30 years old, vaccinated with BCG, who were not at risk of tuberculosis, from regions with low epidemiologic risk (Oryol region, Ryazan region, and Arkhangelsk region). During the study, 4 visits were scheduled for each participant: [Visit 0 (screening), Visit 1, Visit 2 (in 72 h) and Visit 3 (in 28 days)]. All participants, who excluded active and latent tuberculosis infection, underwent a test with RTA. To assess the safety of RTA tests, all systemic and local adverse events that occurred during 28 days were recorded. The trial was filed in the NIH clinical trials database ClinicalTrials.gov (NCT05203068). In individuals with a negative T-SPOT.TB test, the specificity of the RTA test was 97% (95% CI: 92-99%) with a cut-off of >0 mm. The study findings confirm data 2009: 100.00 (95% CI: 94-100). When evaluating the safety of the RTA test during 28 days of follow-up, the participants did not report local and systemic adverse reactions that had a causal relationship with the RTA test. Diaskintest is highly specific and safe, therefore it is a valuable tool as a screening test for early detection of tuberculosis.


Experiences of caregivers of infants who have been on bubble continuous positive airway pressure at Queen Elizabeth Central Hospital, Malawi: A descriptive qualitative study.
An innovative, low-cost bubble continuous positive airway pressure (bCPAP) device has recently been introduced in Malawi for the treatment of respiratory distress in infants. While this novel bCPAP system has been shown to be safe and effective in reducing infant mortality, caregivers' experiences have not been investigated. The purpose of this study was to explore experiences of parents and guardians of infants who had been on bCPAP at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi. This was a descriptive phenomenological study that was carried out at the Chatinkha nursery unit and the paediatric nursery ward at QECH, from January to February 2015. Purposive sampling was used to select participants for in-depth interviews. Data saturation was reached with 12 caregivers. Data were analysed using Colaizzi's framework. Caregivers received inadequate, inconsistent, and sporadic information about bCPAP. Student nurses and doctors were best able to answer caregivers' questions and concerns. When their infants were on bCPAP, caregivers felt anxious and fearful. However, upon implementation of bCPAP treatment for their children, the caregivers were satisfied with it. The main sources of psychological stress were limited parent-child interaction and the constraints of prescribed visiting hours. Family, friends, and caregiver involvement in the care of infants provided some psychological comfort. The results show gaps in the information and psychological support that mothers of infants on bCPAP receive in hospital. We recommend that psychological support be given to the mothers of infants on bCPAP at QECH.


The low-dose model of UVB-induced immunosuppression.
Recent interest in photoimmunology has led to the development of the low-dose model of UVB-induced immunosuppression, an experimental framework in which inhibition of contact hypersensitivity is associated with alterations in the morphology and the antigen-presenting function of Langerhans cells in locally irradiated skin, and with the appearance of hapten-specific T-suppressor cells in systemic circulation. This article reviews the scientific data that has been generated from the utilization of this model. It focuses particular attention on current evidence that identifies distinct epidermal cell populations as key sources of the immunosuppression evoked by low-dose UVB.


Cross-sectional multicentre study on the cohort of all the French junior lecturers in general practice.
General practice became an academic discipline quite recently in many western countries. In France, junior lecturer work is specified in a three-part mandate: medical work in general practice, teaching in the university, and research. Since 2007, 130 junior lecturers have been appointed in general practice. The aim of the creation of junior lecturer status was to align general practice with other specialties and to develop research and education in primary care. To describe the healthcare, teaching and research undertaken by junior lecturers in general practice, practising in October 2014. A cross-sectional multicentre study using an online self-administered questionnaire on the cohort composed of all the junior lecturers in general practice with open questions and the qualitative analysis of written verbatim accounts. Of the 95 junior lecturers practising at the date of the study, 75 (79%) responded; average age 32 years; gender ratio (F/M) 2.4:1. They spent five, two and three half-days per week respectively in healthcare, teaching and research. The healthcare activity was predominantly carried out in the community (73%). Thirty-nine per cent worked as part of a multi-professional team taking on 50 consultations per week. Most of the educational work involved lecturing and mentoring students specializing in general practice (median 86 hours per year). Research output increased during the fellowship. Research topics were varied and relevant to the disciplinary field. During the fellowship, the balancing, and even the reinforcement, of healthcare and research contributions were accompanied by a significant investment in educational provision.


Aerobic bacterial isolates from choledochal bile at a tertiary hospital.
We studied the aerobic bacterial isolates from bile and their susceptibilty pattern in patients with biliary tract disease. Samples of bile collected during endoscopic retrograde cholangio pancreatography (ERCP) and surgery, were inoculated on standard media. Bacterial identification and susceptibility were done by standard techniques. A total of 209 samples were cultured, out of which 128 samples showed growth. Total number of isolates obtained was 221. Poly-microbial infection was detected in 67 patients. Predominant aerobic bacterial isolates obtained were Escherichia coli 30% (67), Klebsiella species 23.98% (53), Enterococcus species 12.21% (27). Multi-drug resistance was noted in 57%. Higher resistance rate was noted among Gram negative bacilli for ampicillin (92.4%), cephalexin (82.46%), ciprofloxacin (68.42%), piperacillin (64.33%). Sensitivity to meropenem was 90.64% and amikacin was 76.61%. Gram positive bacteria showed high resistance to gentamicin (39.53%). Sensitivity to ampicillin was 86.05% and penicillin was 81.4%. Vancomycin and teicoplanin showed 100% sensitivity. From our study we conclude that E. coli, Klebsiella species and Enterococcus species are common pathogens infecting biliary tract. Poly-microbial infection and multi-drug resistance warrants culture and sensitivity to guide antimicrobial therapy. We recommend combination of amikacin and ampicillin for empirical therapy at our institution.


Failing our children: lead in U.S. school drinking water.
Lead is the most prevalent toxicant in U. S. school drinking water. Yet for the vast majority of schools, federal regulation for testing taps and remediating contamination is voluntary. Using school case studies, this article discusses the regulatory vacuum that leaves children unprotected from potential exposure to very high lead doses through consumption of school water. Controlling lead hazards from water fountains, coolers, and other drinking water outlets in schools requires improved sampling protocols that can capture the inherent variability of lead release from plumbing and measure both the particulate and dissolved lead present in water. There is a need to reevaluate the potential public health implications of lead-contaminated drinking water in schools. Accounting for this misunderstood and largely overlooked exposure source is necessary in order to better understand and address childhood lead poisoning in the U. S.


Promoting Health for All Kansans Through Mass Media: Lessons Learned From a Pilot Assessment of Student Ebola Perceptions.
We aimed to assess student knowledge of Ebola virus disease (EVD) and opinions about media coverage of EVD. We conducted a pilot study with a cross-sectional survey and a convenience sample. Sixty-five college students participated in the survey and reported a low level of basic knowledge of EVD, high health literacy levels, and Internet and health professionals as sources for health information. This pilot study was an important first step to understanding students' knowledge of Ebola, common sources of health information, and health literacy levels. Results from this study highlight the need to improve health communication training and further evaluate the quality of health information dissemination via all communication sources. (Disaster Med Public Health Preparedness. 2016;10:641-643).


Ultrasensitive silicon nanowire for real-world gas sensing: noninvasive diagnosis of cancer from breath volatolome.
We report on an ultrasensitive, molecularly modified silicon nanowire field effect transistor that brings together the lock-and-key and cross-reactive sensing worlds for the diagnosis of (gastric) cancer from exhaled volatolome. The sensor is able to selectively detect volatile organic compounds (VOCs) that are linked with gastric cancer conditions in exhaled breath and to discriminate them from environmental VOCs that exist in exhaled breath samples but do not relate to the gastric cancer per se. Using breath samples collected from actual patients with gastric cancer and from volunteers who do not have cancer, blind analysis validated the ability of the reported sensor to discriminate between gastric cancer and control conditions with >85% accuracy, irrespective of important confounding factors such as tobacco consumption and gender. The reported sensing approach paves the way to use the power of silicon nanowires for simple, inexpensive, portable, and noninvasive diagnosis of cancer and other disease conditions.


[Molecular characteristic of duck hepatitis A virus type 1 causing pancreatitis ].
[OBJECTIVE] We studied the molecular characteristics of the full-length genome of duck hepatitis A virus type 1 causing pancreatitis in Muscovy ducklings. [METHODS] We determined the entire genomic sequence of duck hepatitis A virus type 1 strain MPZJ1206 using reverse transcription polymerase chain reaction assay and analyzed the bioinformatics of the viral genome sequence. [ RESULTS] The genome length of strain MPZJ1206 comprised 7703 bases, with a G + C content of 43.05%. The genome of MPZJ1206 contains a single, long open reading frame encoding a polypeptide of 2249 amino acids, with a genomic orgariization similar to those of other isolates of duck hepatitis A virus type 1. MPZJ1206 is identical with previously isolates by 93. 5% - 99. 6% in nucleotide sequence and 97. 9% - 99. 6% in amino acid sequence and shares genetic distance no more than 7%. Phylogenetic analysis based on genome sequence indicates that MPZJ1206 shares a close genetic relationship with two strains isolated in 2011. [CONCLUSION] Although pathotype caused by MPZJ1206 strain is significantly distinct from those induced by classical isolates of duck hepatitis A virus type 1, the genome of MPZJ1206 shares high homology with those of previous isolates. The change of pathotype may result from an alteration in viral tissue tropism of MPZJ1206.


The efficacy and safety of neoadjuvant chemotherapy on patients with advanced gastric cancer: A multicenter randomized clinical trial.
Exploring the efficacy and safety of perioperative chemotherapy on patients with AGC at different clinical and pathological stages. A phase III randomized, multicenter, trial comparing adjuvant (arm A) or perioperative S-1 plus oxaliplatin (SOX, arm B), and perioperative capecitabine plus oxaliplatin (XELOX, arm C) was initiated in T3/4, node + gastric cancer patients (unclear). Each patient received an 8-cycle chemotherapy (3 weeks for one cycle). Group arms B and C received two cycles preoperatively, and six cycles postoperatively. Primary endpoints were R0 resection rate and DFS, and secondary endpoints included OS, ORR, DCR, and safety. This study was registered on Clinicaltrials.gov. NCT01516944. A total of 749 patients were randomly assigned into groups A, B, and C. Group A received 1460 circles chemotherapy and group B received 1177 circles while group C received 1200 circles. R0 resection rates in the three groups were 81.7%, 88.7%, and 83.1%, respectively. The difference between groups A and B was considered to be statistically significant (P = .018), and no significant difference between groups B and C (P = .051). Hazard ratio were compared between groups B and C and DFS showed 0.72 (0.67-0.77 with 95% CI), Pnon-inferiority < .0001, Plog-rank = .064). The CI top limit actually lower than the estimated value of 1.38, which indicated noninferiority of SOX to XELOX. Compared with PAC, perioperative chemotherapy showed a significant improvement in R0 resection rates and prognosis in AGC patients with higher safety rates. This study was powered to show superiority of perioperative over adjuvant SOX, and noninferiority of SOX to XELOX. Volume measurement, repeated laparoscopic exploration combined with exfoliative cytology can be used as a supplementary method in the clinical staging and efficacy evaluation of AGC.


POLONIUM-210: A VOLATILE RADIOELEMENT IN CIGARETTES.
Polonium-210, which emits alpha particles, is a natural contaminant of tobacco. For an individual smoking two packages of cigarettes a day, the radiation dose to bronchial epithelium from Po(210) inhaled in cigarette smoke probably is at least seven times that from background sources, and in localized areas may be up to 1000 rem or more in 25 years. Radiation from this source may, therefore, be significant in the genesis of bronchial cancer in smokers.


Butyrate reduces liver metastasis of rat colon carcinoma cells in vivo and resistance to oxidative stress in vitro.
Injection of the rat colon carcinoma cell line CC531 into spleen of syngeneic rats results in considerable amounts of liver metastases within 14 days. We investigated whether preincubation of the cells with butyrate reduced their metastatic ability in vivo and whether this was accompanied by reduction in related properties such as secretion of metalloproteinases and their ability to withstand oxidative stress. Butyrate incubation reduced cell growth rate and initiated apoptosis in a dose- and time-related manner, but proliferation was retrieved when cultivation was continued in medium without butyrate. Splenic injection of butyrate treated, proliferating cells resulted in significantly reduced amounts of tumor mass compared to untreated cells. The butyrate treated cells were more susceptible to oxidative stress than control cells, as demonstrated by increased number of apoptotic cells and reduced cell growth after exposure to menadione. A reduction in cellular glutathione was found after prolonged incubation with butyrate. Butyrate appeared not to alter the secretion of active metalloproteinases from the cells although an apparent increase in proforms was demonstrated. Neither did butyrate alter the synthesis of metalloproteinase inhibitors. Lastly, a reduced adhesion of the tumor cells to collagen coated matrix was found after butyrate treatment. Thus, the inhibitory effects of butyrate on tumor malignancy are caused by a diversity of mechanisms.


The Human Face of Health News: A Multi-Method Analysis of Sourcing Practices in Health-Related News in Belgian Magazines.
Health journalists are central gatekeepers who select, frame, and communicate health news to a broad audience, but the selection and content of health news are also influenced by the sources journalists, rely on (Hinnant, Len-Rios, & Oh, 2012). In this paper, we examine whether the traditional elitist sourcing practices (e.g., research institutions, government) are still important in a digitalized news environment where bottom-up non-elite actors (e.g., patients, civil society organizations) can act as producers (Bruns, 2003). Our main goal, therefore, is to detect whether sourcing practices in health journalism can be linked with strategies of empowerment. We use a multi-method approach combining quantitative and qualitative research methods. First, two content analyses are developed to examine health-related news in Belgian magazines (popular weeklies, health magazines, general interest magazines, and women's magazines). The analyses highlight sourcing practices as visible in the texts and give an overview of the different stakeholders represented as sources. In the first wave, the content analysis includes 1047 health-related news items in 19 different Belgian magazines (March-June 2013). In the second wave, a smaller sample of 202 health-related items in 10 magazines was studied for follow-up reasons (February 2015). Second, to contextualize the findings of the quantitative analysis, we interviewed 16 health journalists and editors-in-chief. The results illustrate that journalists consider patients and blogs as relevant sources for health news; nonetheless, elitist sourcing practices still prevail at the cost of bottom-up communication. However, the in-depth interviews demonstrate that journalists increasingly consult patients and civil society actors to give health issues a more "human" face. Importantly, the study reveals that this strategy is differently applied by the various types of magazines. While popular weeklies and women's magazines give a voice to ordinary citizens to translate complex issues and connect with their audiences, general interest magazines and health magazines prefer elite sources and use ordinary citizen stories as a way of "window dressing."


Quantitative analysis of retinal vessel attenuation in eyes with retinitis pigmentosa.
Retinal vessel attenuation is a key finding in the diagnosis of retinitis pigmentosa (RP), but there have been no studies to determine whether quantitative measurement of this retinal sign is useful. We aimed to investigate retinal vessel caliber and its relationship with the severity of RP. This is a cross-sectional study based on 74 patients (145 eyes) with RP who had visual field assessment with Goldmann permeter and good-quality retinal images for vessel size measurements identified by retrospective medial chart review (1973-2007) in the electrophysiology clinic of a tertiary eye hospital in Australia. Retinal vessel calibers were measured using a computer-based program as the central retinal artery and vein equivalent (CRAE and CRVE). Goldmann visual field area for III4e white test light was measured quantitatively using ImageJ software as a clinical parameter to indicate the severity of RP. We used the generalized estimating equation models to estimate the difference in retina vessel calibers accounting for correlation between right and left eyes. Mean CRAE and CRVE were significantly narrower in persons with smaller visual field area. For each 100 cm2 decrease in visual field area, CRAE and CRVE decreased by -15.2 μm (95% confidence interval -20.7, -9.78) and -26.8 μm (-35.1, -18.5), respectively (both P<0.001). In RP patients, the severity of visual field loss is correlated with retinal vessel attenuation. Quantitative retinal vessel caliber measurement may be a useful additional clinical marker for monitoring progression of RP or potential treatment response.


Induction of insulin autoantibodies and protection from diabetes with subcutaneous insulin B:9-23 peptide without adjuvant.
Insulin B chain peptide B:9-23 given with incomplete Freund's adjuvant (IFA) subcutaneously to NOD and BALB/c mice induces insulin autoantibodies (IAA). We also found that subcutaneous administration of the peptide without adjuvant induced IAA in normal BALB/c mice. The autoantibodies react with intact insulin and cannot be absorbed by the B:9-23 peptide. With the induction of IAA by the self-peptide without adjuvant, we hypothesized that the peptide given subcutaneously without adjuvant would prevent the development of diabetes mellitus in NOD mice. The peptide B:9-23, when given in standard doses of 100 microg and low doses of 10 microg, protected female NOD mice versus unvaccinated controls from diabetes. Presently, NOD mice vaccinated with the standard dose and the low dose have a 44% and 60% survival, respectively, at 26 weeks compared to controls with a 10% diabetes-free survival at 22 weeks (n = 10 for each group, P < 0.001 for both vaccine doses). As expected, the level of IAA expressed was significantly higher for the vaccinated mice versus the control group. We conclude that insulin B chain peptide B:9-23 can confer protection from diabetes in NOD mice even when administered subcutaneously without adjuvant.


Amyotrophic lateral sclerosis progression and stability of brain-computer interface communication.
Our objective was to investigate the relationship between brain-computer interface (BCI) communication skill and disease progression in amyotrophic lateral sclerosis (ALS). We sought also to assess stability of BCI communication performance over time and whether it is related to the progression of neurological impairment before entering the locked-in state. A three years follow-up, BCI evaluation in a group of ALS patients (n = 24) was conducted. For a variety of reasons only three patients completed the three years follow-up. BCI communication skill and disability level, using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, were assessed at admission and at each of the three follow-ups. Multiple non-parametric statistical methods were used to ensure reliability of the dependent variables: correlations, paired test and factor analysis of variance. Results demonstrated no significant relationship between BCI communication skill (BCI-CS) and disease evolution. The patients who performed the follow-up evaluations preserved their BCI-CS over time. Patients' age at admission correlated positively with the ability to achieve control over a BCI. In conclusion, disease evolution in ALS does not affect the ability to control a BCI for communication. BCI performance can be maintained in the different stages of the illness.


Alternative sigma factor σE has an important role in stress tolerance of Yersinia pseudotuberculosis IP32953.
Yersinia pseudotuberculosis is an important pathogen that probably survives well in the modern food chain. However, little is known about the mechanisms that allow the growth of this pathogen in foods under stress conditions. The expression of rpoE encoding σ(E) was defined by quantitative real-time reverse transcription-PCR. Expression of rpoE was induced at 3°C, 37°C, and 42°C, under exposure to 3% NaCl, 3% ethanol, or high and low pH, in relation to its expression at the optimum growth temperature of 28°C of Y. pseudotuberculosis. Mutation of rpoE either impaired or abolished growth under stresses caused by low or high temperature, low pH, and ethanol. In addition, the growth temperature range of the mutant was significantly diminished compared to that of the wild-type strain IP32953. The results were confirmed with complementation of the mutant. Thus, σ(E) plays a significant role in the stress tolerance of Y. pseudotuberculosis IP32953 and probably contributes to the survival of this pathogen in the food chain.


[Effect of inhibiting brain reactive oxygen species on sympathetic nerve activity in DOCA-salt hypertensive rats].
To investigate whether brain reactive oxygen species mediate sympathoexcitation and arterial pressure elevation in DOCA-salt hypertensive rats. DOCA-salt hypertensive model was established in male SD rats by subcutaneous injection of DOCA after uninephrectomy and drinking 1% NaCl solution for 4 weeks. The baseline mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded in the rats under mild anesthesia, and MAP changes following intravenous hexamethonium injection were observed. The responses of MAP, HR and RSNA to intracerebroventricular administration of tempol (20 µmol/L in 10 µl) were evaluated; plasma NE level was measured with ELISA, and ROS level and NAD(P)H oxidase activity in the hypothalamus were detected using chemiluminescence assay. MAP and plasma NE levels were significantly increased in DOCA-salt rats as compared with those in the control group (P<0.01). In DOCA-salt hypertensive rats, intravenous hexamethonium injection induced a blood pressure reduction 240% of that in control rats, and significantly increased the levels of superoxide anion and NAD(P)H oxidase activity in the hypothalamus. Intracerebroventricular microinjection of tempol also resulted in more significant changes of MAP, HR and RSNA in DOCA-salt rats than in the control group (P<0.01). Sympathoexcitation due to increased NAD(P)H oxidase-derived ROS levels in the hypothalamus may mediate arterial pressure elevation in DOCA-salt hypertensive rats.


Effect of pharmacy practice residency training on residents' knowledge of and interest in clinical research.
The effect of pharmacy practice residency training on subjectively and objectively assessed research knowledge, skills, and interests of residents was studied. A preintervention versus post-intervention design was used. Residency year 2004- 05 residents were administered a validated Web-based survey at the beginning of residency and again at the end of residency. The survey collected resident responses to questions regarding resident and residency characteristics, subjective assessments of specific professional skills and research skills and knowledge, and objective assessments of basic research knowledge. For residents who completed beginning and end of residency surveys, results were linked when possible to allow for paired and unpaired statistical analyses. Totals of 346 (33.2% response rate) and 222 (21.3% response rate) surveys were completed at the beginning and the end of the residency, respectively, with 129 respondents completing both. Statistically significant improvements were observed for the total and paired population in subjectively assessed research-related skills and abilities and general professional skills. Subjectively assessed understanding of specific statistical tests revealed a significant improvement. Total population analysis and paired population analysis revealed no changes in objectively assessed research-related knowledge from the beginning of the residency to the end of the residency. Although there was improvement from the beginning to the end of residency in subjectively assessed research-related skills and abilities and in self-assessed understanding of most statistical tests, the end of residency objectively assessed research-related knowledge scores were unchanged. Residents' expectations that the residency would increase research knowledge, skills, and desire for research involvement were unmet. These results suggest that training based on residency program standards may not increase residents' interest or provide them with the skills necessary to participate in clinical research.


Ferroelectric Polarized in Transistor Channel Polarity Modulation for Reward-Modulated Spike-Time-Dependent Plasticity Application.
Reward signals reflect the developmental tendency of reinforcement learning (RL) agents. Reward-modulated spike-time-dependent plasticity (R-STDP) is an efficient and concise information processing feature in RL. However, the physical construction of R-STDP normally demands complex circuit design engineering, resulting in large power consumption and large area. In this work, we studied the role of ferroelectric polarization in the modulation of carbon nanotube transistor channel polarity. Furthermore, we applied a modulating channel method to construct a 2T synaptic component by spin-coating technology. Based on the nonvolatility of ferroelectric polarization, the synaptic component constructed has the characteristics of reconfigurable polarity. One channel could be modulated to n-type and the other to p-type. One modulated channel was used to perform the STDP function when the reward signal arrived, and the other modulated channel was used to perform the anti-STDP function when the punishment signal arrived. Finally, R-STDP learning rules are implemented on hardware. This work provides a strategy for hardware construction of RL.


Pathophysiology of chronic subdural haematoma: inflammation, angiogenesis and implications for pharmacotherapy.
Chronic subdural haematoma (CSDH) is an encapsulated collection of blood and fluid on the surface of the brain. Historically considered a result of head trauma, recent evidence suggests there are more complex processes involved. Trauma may be absent or very minor and does not explain the progressive, chronic course of the condition. This review focuses on several key processes involved in CSDH development: angiogenesis, fibrinolysis and inflammation. The characteristic membrane surrounding the CSDH has been identified as a source of fluid exudation and haemorrhage. Angiogenic stimuli lead to the creation of fragile blood vessels within membrane walls, whilst fibrinolytic processes prevent clot formation resulting in continued haemorrhage. An abundance of inflammatory cells and markers have been identified within the membranes and subdural fluid and are likely to contribute to propagating an inflammatory response which stimulates ongoing membrane growth and fluid accumulation. Currently, the mainstay of treatment for CSDH is surgical drainage, which has associated risks of recurrence requiring repeat surgery. Understanding of the underlying pathophysiological processes has been applied to developing potential drug treatments. Ongoing research is needed to identify if these therapies are successful in controlling the inflammatory and angiogenic disease processes leading to control and resolution of CSDH.