Human osteoblast-like cells phagocytose metal particles and express the macrophage marker CD68 in vitro.
Periprosthetic osteolysis is a major cause of aseptic loosening in artificial joint replacement. It is assumed to occur in conjunction with the activation of macrophages. We have shown in vitro that human osteoblast-like cells, isolated from bone specimens obtained from patients undergoing hip replacement, phagocytose fine particles of titanium alloy (TiAlV). The human osteoblast-like cells were identified immunocytochemically by the presence of bone-specific alkaline phosphatase (BAP). With increasing duration of culture, a variable number of the osteoblastic cells became positive for the macrophage marker CD68, independent of the phagocytosis of particles, with a fine granular cytoplasmic staining which was coexpressed with BAP as revealed by immunodoublestaining. The metal particles were not toxic to the osteoblastic cells since even in culture for up to four weeks massively laden cells were vital and had a characteristic morphology. Cells of the human osteosarcoma cell line (HOS 58) were also able to phagocytose metal particles but had only a low expression of the CD68 antigen. Fluorescence-activated cell scanning confirmed our immunocytochemical results. Additionally, the cells were found to be negative for the major histocompatibility complex-II (MHC-II) which is a marker for macrophages and other antigen-presenting cells. Negative results of histochemical tests for tartrate-resistant acid phosphatase excluded the contamination by osteoclasts or macrophages in culture. Our observations suggest that the osteoblast can either change to a phagocytosing cell or that the phagocytosis is an underestimated property of the osteoblast. The detection of the CD68 antigen is insufficient to prove the monocytic lineage. In order to discriminate between macrophages and osteoblasts additional markers should be used. To our knowledge, this is the first demonstration of cells of an osteoblastic origin which have acquired a mixed phenotype of both osteoblasts and macrophages.


Inhibition of endoplasmic reticulum associated degradation reduces endoplasmic reticulum stress and alters lysosomal morphology and distribution.
Disturbances in proteostasis are observed in many neurodegenerative diseases. This leads to activation of protein quality control to restore proteostasis, with a key role for the removal of aberrant proteins by proteolysis. The unfolded protein response (UPR) is a protein quality control mechanism of the endoplasmic reticulum (ER) that is activated in several neurodegenerative diseases. Recently we showed that the major proteolytic pathway during UPR activation is via the autophagy/lysosomal system. Here we investigate UPR induction if the other major proteolytic pathway of the ER -ER associated degradation (ERAD)-is inhibited. Surprisingly, impairment of ERAD results in decreased UPR activation and protects against ER stress toxicity. Autophagy induction is not affected under these conditions, however, a striking relocalization of the lysosomes is observed. Our data suggest that a protective UPR-modulating mechanism is activated if ERAD is inhibited, which involves lysosomes. Our data provide insight in the cross-talk between proteolytic pathways involved in ER proteostasis. This has implications for neurodegenerative diseases like Alzheimer's disease where disturbed ER proteostasis and proteolytic impairment are early phenomena in the pathology.


Characterization of cerebral aneurysms for assessing risk of rupture by using patient-specific computational hemodynamics models.
Hemodynamic factors are thought to play an important role in the initiation, growth, and rupture of cerebral aneurysms. This report describes a pilot clinical study of the association between intra-aneurysmal hemodynamic characteristics from computational fluid dynamic models and the rupture of cerebral aneurysms. A total of 62 patient-specific models of cerebral aneurysms were constructed from 3D angiography images. Computational fluid dynamics simulations were performed under pulsatile flow conditions measured on a normal subject. The aneurysms were classified into different categories, depending on the complexity and stability of the flow pattern, the location and size of the flow impingement region, and the size of the inflow jet. The 62 models consisted of 25 ruptured and 34 unruptured aneurysms and 3 cases with unknown histories of hemorrhage. The hemodynamic features were analyzed for associations with history of rupture. A large variety of flow patterns was observed: 72% of ruptured aneurysms had complex or unstable flow patterns, 80% had small impingement regions, and 76% had small jet sizes. By contrast, unruptured aneurysms accounted for 73%, 82%, and 75% of aneurysms with simple stable flow patterns, large impingement regions, and large jet sizes, respectively. Aneurysms with small impingement sizes were 6.3 times more likely to have experienced rupture than those with large impingement sizes (P = .01). Image-based patient-specific numeric models can be constructed in an efficient manner that allows clinical studies of intra-aneurysmal hemodynamics. A simple flow characterization system was proposed, and interesting trends in the association between hemodynamic features and aneurysmal rupture were found. Simple stable patterns, large impingement regions, and jet sizes were more commonly seen with unruptured aneurysms. By contrast, ruptured aneurysms were more likely to have disturbed flow patterns, small impingement regions, and narrow jets.


Ooplasmic transfer in mature human oocytes.
Ooplasmic transplantation aimed at restoring normal growth in developmentally compromised oocytes and embryos was evaluated in seven couples (eight cycles) with multiple implantation failures. Two approaches were investigated to transfer ooplasm from donor eggs at metaphase II (MII) stage into patient MII eggs: (i) electrofusion of a ooplasmic donor fragment into each patient egg (three cycles), and (ii) direct injection of a small amount of ooplasm from a donor egg into each patient egg (five cycles). Some donor eggs were used multiple times. Donor eggs were divided into two groups, one being used for ooplasmic extraction and the other one for egg donation. Cleaved embryos resulting from the latter were cryopreserved, where numbers and satisfactory development permitted. A second control group consisted of embryos derived from patient eggs after intracytoplasmic sperm injection without ooplasmic transfer. This was performed when sufficient number of eggs were available (n = 5). Donor eggs (n = 40) were evaluated cytogenetically after micromanipulation in order to confirm the presence of chromosomes. One egg was anuclear and the recipient embryos were not transferred. Normal fertilization was significantly higher after injection of ooplasm (63%) in comparison with fusion (23%). Pronuclear anomalies appeared enhanced after fusion with ooplasts. Embryo morphology was not improved in the three cycles with electrofusion and patients did not become pregnant. An improvement in embryo morphology was noted in two patients after injection of ooplasm and both became pregnant, but one miscarried. A third pregnancy was established in the repeat patient, without obvious embryo improvement. One baby was born and the third pregnancy is ongoing with a normal karyotype. Two other patients with male factor infertility had poor embryos after ooplasmic injection, but the donor embryo controls were also poor. The patients did not become pregnant and had no donor embryos frozen. Ooplasmic transfer at the MII stage may be promising in patients with compromised embryos; however, evaluation of ooplasmic anomalies and optimization of techniques will require further investigation prior to widescale application.


Medication Palatability Affects Physician Prescribing Preferences for Common Pediatric Conditions.
The objective of this study was to determine if physicians would alter their prescribing preferences after sampling liquid formulations of medications for common pediatric diagnoses. This was a prospective interventional before/after study conducted at an academic medical center in the United States. The participants of interest included emergency, family medicine, and pediatric physicians. Participants initially completed a brief survey for their primary oral liquid medication of choice for the treatment of selected disease states. These included otitis media, sinusitis, cellulitis, asthma, colitis, and pneumonia. Participants were asked to choose one of the medication options for each disease and then were given all medications to sample for a taste test. The prescribing preference survey was then repeated. The primary outcome was change in prescribing. McNemar's test was used to evaluate change in proportion of medications chosen before and after taste testing. There were 101 physicians who participated in the study. There were three conditions for which participants changed their prescribing preferences significantly. These were otitis media (change from amoxicillin to cefdinir, difference = 13.2%, 95% confidence interval [CI] = 5.5% to 21.0%), asthma exacerbation (change from dexamethasone or prednisone to prednisolone, 28%, 95% CI = 15.9% to 40.1%), and pneumonia (change from azithromycin to amoxicillin, 16.0%, 95% CI = 6.4% to 25.6%). There was no significant change with respect to the other scenarios. Physicians showed preferences for certain pediatric medications based on taste and showed significant changes in prescribing preferences for some common pediatric diagnoses after tasting different medications for these conditions.


Elimination of local macrophages in intestine prevents chronic colitis in interleukin-10-deficient mice.
Uncontrolled activation of T cells and macrophages is involved in the development of inflammatory bowel disease (IBD). However, the precise role of intestinal macrophages for development of IBD is till unclear. To investigate the role of local macrophages for development of IBD, we developed poly-D, L-lactic acid microspheres containing dichloromethylene diphosphonate, which was specifically taken up by macrophages and depleted them, and then the animal model for human IBD was treated with this reagent. We have shown that rectal administration of the microspheres reduced the numbers of resident macrophages in the intestinal lymphoid follicles of interleukin-10-deficient mice. Importantly, depletion of intestinal macrophages was associated with suppression of development of chronic colitis. These results suggest that local macrophages in the intestine play a critical role in the development of chronic colitis in an animal model for IBD. Our study implies that elimination of resident macrophages in the intestine may become a therapeutic approach to IBD.


Correlations of hippocampal atrophy and focal low-frequency magnetic activity in Alzheimer disease: volumetric MR imaging-magnetoencephalographic study.
Patients with Alzheimer disease (AD) have more low-frequency activity on conventional EEG and increased focal magnetoencephalographic (MEG) dipole density (DD) in delta and theta bands. This activity concurs with atrophy and reduced metabolic and perfusion rates, particularly in temporoparietal structures. The relationship between functional and structural measures and their conjoined capability to improve the diagnosis of AD were assessed in this study. Whole-head MEG recordings were obtained in 15 patients in whom the diagnosis of AD had been made and in 16 healthy control subjects during a resting condition. MR imaging volumetric data were also obtained; these included global cerebral, temporal lobe, and hippocampal volumes. DD in the delta and theta bands was enhanced in the AD group compared with the healthy control subjects. Slow-wave activity differed significantly between the groups in the temporoparietal regions of both hemispheres. Left hippocampal volume was correlated with left temporal and parietal delta DD and left temporal theta DD. A combination of left hippocampal volume and left temporal theta DD enabled correct classification in 87.1% of the patients with AD or control subjects. Results support the predominant role of temporoparietal hypofunction as defined by DD and hippocampal structural deficits shown on MR images in patients with AD. A multidisciplinary perspective of different techniques may improve our understanding of the disease and our diagnostic abilities.


Roe deer sera used for TBE surveillance in Austria.
A large majority of Austrian citizens are aware of tick-borne encephalitis (TBE), consequently reflected by a high vaccination rate of 85%. In return, risk assessment and disease mapping on human cases might be hampered due to high and inhomogeneous vaccination rates and travel habitats of humans. The roe deer was used to obtain a starting point for the integral view on the actual risk of TBE in Austria. The roe deer exhibits several attributes which makes it suitable as an indicator species: the roe deer has a restricted home range and it is known to be a heavy tick carrier. Furthermore it sero-converts after infection with TBE, but no outbreak occurs. Sera from 945 roe deer were obtained from all over Austria and screened with IFAT for the antibodies against TBE. Twenty-two positive samples, 2.4%, and 17 samples at the borderline titre of 1:16 were identified. The majority of the positive samples, 70.6%, were located in known TBE areas based on human cases. Further research is needed to confirm or reject new endemic foci of TBE transmission.


Evaluation of a highly soluble calcium source and phytase in the diets of broiler chickens.
An experiment was conducted to evaluate the influence of a highly soluble Ca (HSC) source on performance, bone ash and mineralization, and apparent ileal digestibility of Ca, P, N, and energy in Ross 708 broiler chickens. Dietary Ca was supplied by the HSC source and monocalcium phosphate to provide 4 levels of Ca (0.45, 0.60, 0.75, or 0.90%). Available P (aP) was maintained at 0.32% in all the diets. Each diet was supplemented with 0, 500, or 2,500 U/kg of phytase as a 4 × 3 factorial. An additional diet was formulated using limestone to contain 0.90% Ca and 0.45% aP as a positive control (PC). Diets were fed to 7 replicate cages of 8 birds per cage from d 0 to 21 posthatch. Feed intake (FI) was linearly (P ≤ 0.05) reduced, and BW gain was quadratically (P ≤ 0.05) reduced as Ca from HSC increased from 0.45 to 0.90%. Phytase supplementation linearly (P ≤ 0.05) increased FI and BW gain and improved feed conversion ratio. Tibia ash and P weights were lower in birds fed 0.90% Ca from HSC compared with broilers fed 0.90% Ca from limestone. Phytase supplementation increased tibia ash and P weights in broilers fed 0.60, 0.75, or 0.90% HSC (Ca level × phytase P ≤ 0.05). Phytase supplementation linearly (P ≤ 0.05) increased tibia Ca weight. Reducing HSC from 0.90 to 0.45% or increasing phytase supplementation linearly (P ≤ 0.05) improved ileal P digestibility. Ileal Ca digestibility increased linearly only in broilers fed 0.45% Ca from HSC as phytase supplementation increased (Ca level × phytase P ≤ 0.05). Nitrogen or energy digestibility were quadratically (P ≤ 0.05) influenced as HSC or phytase increased. In conclusion, feeding HSC with phytase allowed for reductions in dietary Ca while maintaining broiler performance and bone ash. In addition, P digestibility and P in the bones were increased in broilers fed reduced dietary Ca in the presence of phytase.


A Veterans' Healthcare Administration (VHA) antibiotic stewardship intervention to improve outpatient antibiotic use for acute respiratory infections: A cost-effectiveness analysis.
The Core Elements of Outpatient Antibiotic Stewardship provides a framework to improve antibiotic use, but cost-effectiveness data on implementation of outpatient antibiotic stewardship interventions are limited. We evaluated the cost-effectiveness of Core Element implementation in the outpatient setting. An economic simulation model from the health-system perspective was developed for patients presenting to outpatient settings with uncomplicated acute respiratory tract infections (ARI). Effectiveness was measured as quality-adjusted life years (QALYs). Cost and utility parameters for antibiotic treatment, adverse drug events (ADEs), and healthcare utilization were obtained from the literature. Probabilities for antibiotic treatment and appropriateness, ADEs, hospitalization, and return ARI visits were estimated from 16,712 and 51,275 patient visits in intervention and control sites during the pre- and post-implementation periods, respectively. Data for materials and labor to perform the stewardship activities were used to estimate intervention cost. We performed a one-way and probabilistic sensitivity analysis (PSA) using 1,000,000 second-order Monte Carlo simulations on input parameters. The proportion of ARI patient-visits with antibiotics prescribed in intervention sites was lower (62% vs 74%) and appropriate treatment higher (51% vs 41%) after implementation, compared to control sites. The estimated intervention cost over a 2-year period was $133,604 (2018 US dollars). The intervention had lower mean costs ($528 vs $565) and similar mean QALYs (0.869 vs 0.868) per patient compared to usual care. In the PSA, the intervention was dominant in 63% of iterations. Implementation of the CDC Core Elements in the outpatient setting was a cost-effective strategy.


Personality disorder--not otherwise specified evidence of validity and consideration for DSM-5.
Personality disorder-not otherwise specified (PD-NOS) has received little study despite being a very prevalent diagnosis of personality disorder (PD). Although some studies suggest that PD-NOS is intermediate in severity between subjects with, and without, formal PD, studies examining a comprehensive set of measures and control subjects have not been reported. Nearly 800 subjects were studied with semi-structured diagnostic interviews and with a variety of measures of temperament, character, and specific dimensions of personality and behavior. The subjects were divided into healthy controls (n = 176), Axis I controls (n = 87), PD subjects (n = 344) and PD-NOS subjects (n = 177). Subjects who met General Diagnostic Criteria for Personality Disorder (GDCPD), but not criteria for any one, specific PD, were designated as PD-NOS. On nearly all measures, PD-NOS differed from Healthy and from Axis I Controls in the direction of more pathology. Although subjects meeting criteria for specific PDs appeared more pathological than PD-NOS, this was always due to severity of PD as reflected by the Structured Interview for the Diagnosis of DSM Personality 4 severity score. When compared with subjects with only one specific PD diagnosis, subjects with PD-NOS did not differ in any way. When diagnosed by GDCPD, subjects with PD-NOS are similar to subjects with specific personality disorders and differ, as expected, from Healthy and Axis I Controls on measures of psychosocial function and on various dimensions of personality and related behavior. Accordingly, PD-NOS by GDCPD is as valid a PD as any other specific PD by DSM criteria.


Information needs and problem solving behavior of parents of infants.
Two approaches were used to investigate the problems or issues that parents of infants encounter: the study of circumstances that are naturally recognized by the parent as an issue, and the study of simulated problems concerning commonly occurring infant care issues. A paradigm of problem solving behavior was used to formulate the component of a descriptive study for the purpose of examining the problem solving behavior of mothers during their infants' first 3 months. Mothers who participated in both studies were married or living with a partner, were 17 years or older, and had healthy infants. The objective of the first study was to capture in the mothers' own terms their specification and description of the issues on which they were working and the nature of the infant care task, including the types of help mothers used and the stressors and supports they experienced. Logs were used by 62 mothers (38 primiparae and 24 multiparae) for 90 days after their infants' births to record these issues, types of help, stressors, and supports. Predetermined categories were used to code the data. The type of help used varied significantly by category of issue. Books were used most frequently for issues of growth and development and baby care, and they were used more often than all types of clinicians combined for these types of issues. For over one-third of issues, no help of any type was used. Multiparae and primiparae did not differ significantly in the total number of issues reported, nor in the frequency with which help was used. The objective of the second study was to examine the types of goals and decision making rules that mothers applied to two simulated infant care problems: one concerning the amount of the feeding, and the second concerning noncontingent crying. Four simulated problem exercises were presented to 22 mothers (14 primiparae and 8 multiparae), using a telephone interview in the infants' first 3 months. The results of the study revealed that mothers gave a variety of names to the same problem. The types of goals that mothers identified varied by type of problem. More mothers cited competence as a goal for the crying than the feeding problem. More mothers were able to state the decision rule they had used for naming the problem than for choice of action to solve the problem (implementing).(ABSTRACT TRUNCATED AT 400 WORDS)


Does caffeine enhance bowel recovery after elective colorectal resection? A prospective double-blinded randomized clinical trial.
Postoperative ileus is a common condition following abdominal surgery. Previous studies have shown the positive effects of coffee on gastrointestinal motility. The aim of this study was to assess whether caffeine is the stimulatory agent in coffee that triggers bowel motility and thus may reduce the duration of postoperative ileus. This was a single-centered, prospective, randomized controlled, double-blinded clinical trial. Patients scheduled to undergo elective laparoscopic colectomy between November 2017 and March 2019 were randomly assigned to receive either oral caffeine (100 mg three times daily) or placebo following the procedure. Primary endpoints were time to first flatus and time to first bowel movement. Secondary endpoints were time to tolerate a solid, low-residue diet and length of hospital stay. Registration number: NCT03097900. Seventy patients were included, [35 males, median age 56 years (range 19-79 years)]. After the exclusion of 12 patients, there were 30 patients in the caffeine group and 28 patients in the placebo group. The first passage of stool in the caffeine group occurred 18 h earlier than in the placebo group (p = 0.012); other endpoints did not reach statistical significance. No caffeine-related adverse events were observed. Caffeine consumption following colectomy is safe, leads to a significantly shorter time to first bowel movement, and may thus potentially lead to a shorter postoperative hospital stay.


The role of free oxygen radicals in the aetiopathogenesis of rosacea.
A possible link between superoxide dismutase activity and malondialdehyde level with the clinical manifestations of rosacea was investigated. We found differences in superoxide dismutase activities between mild rosacea (stages I and II) and severe involvement (stage III) groups, as well as between disease and control groups that were statistically significant (P < 0.05). In the mild involvement group (stages I and II), the superoxide dismutase activity was higher than in the control group (P < 0.05), while the malondialdehyde levels did not differ from the control. In the severe involvement group (stage III), the superoxide dismutase activity was lower than in the control group (P < 0.05), and this was coupled to a raised level of malondialdehyde (P < 0.05). These findings clearly show that in the mild involvement phase of rosacea patients, superoxide dismutase activity was stimulated to protect the skin against reactive oxygen species so that the malondialdehyde levels were maintained. In contrast, in more severe disease, due to a decrease in the capacity of the antioxidant defence system, the malondialdehyde levels were increased. These findings support the 'antioxidant system defect hypothesis' in rosacea patients.


[Evaluation of change by patients and staff and specialist physicians in psychosomatic rehabilitation--a catamnestic comparison].
Considering three single outcome criteria reflecting the change of a) physical state, b) general condition and c) ability to work catamnestic ratings of patients and of external doctors are compared. The ratings were assessed by questionnaires 12 months after the end of inpatient psychosomatic treatments ("direct measurement of change"). Mayor findings are: a) the judgements of both data sources indicated positive change or improvement for a majority of patients, b) the ratings of the external doctors were more favourable than the patients' self-ratings, c) moderate but statistically significant correlations between the ratings of the two groups of judges were to be observed. From a more methodological point of view it will be attempted to analyze the meaning of these correlations somewhat more in detail.


Quantitative neuropathologic correlates of changes in ratio of N-acetylaspartate to creatine in macaque brain.
To elucidate the neuropathologic basis of transient changes in the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the primate brain by using a simian immunodeficiency virus (SIV)-infected macaque model of the neurologic manifestation of acquired immune deficiency syndrome. This study was approved by the Massachusetts General Hospital Subcommittee on Research and Animal Care and the Institutional Animal Care and Use Committee of Harvard University. Rhesus macaques infected with SIV were evaluated during the 1st month of infection. A total of 11 animals were studied, including four control animals, three animals sacrificed 12 days after infection, three animals sacrificed 14 days after infection, and one animal sacrificed 28 days after infection. All animals underwent in vivo proton ((1)H) magnetic resonance (MR) spectroscopy, and postmortem frontal lobe tissue was investigated by using high-spectral-resolution (1)H MR spectroscopy of brain extracts. In addition, quantitative neuropathologic analyses were performed. Stereologic analysis was performed to determine neuronal counts, and immunohistochemical analysis was performed to analyze three neuronal markers: synaptophysin, microtubule-associated protein 2 (MAP2), and calbindin. Analysis of variance (ANOVA) was used to determine substantial changes in neuropathologic and MR spectroscopic markers. Spearman rank correlations were calculated between plasma viral load and neuropathologic and spectroscopic markers. During acute infection with SIV, the macaque brain exhibited significant changes in NAA/Cr (P < .02, ANOVA) and synaptophysin (P < .013, ANOVA). There was no significant change in the concentration of Cr. No significant changes were found in neuronal counts or other immunohistochemical neuronal markers. With the Spearman rank test, a significant direct correlation was detected between synaptophysin and ex vivo NAA/Cr (r(s) = 0.72, P < .013). No correlation between NAA/Cr and neuronal counts, calbindin, or MAP2 was found. NAA/Cr is a sensitive marker of neuronal injury, not necessarily neuronal loss, and best correlates with synaptophysin, a marker of synaptodendritic dysfunction.


The structural subunit of glucose-6-phosphate dehydrogenase (baker's yeast).
The subunit molecular weight of glucose-6-phosphate dehydrogenase (G6PD) from baker's yeast has been evaluated. The subunit molecular weight value is shown to be 25,500 daltons by analytical ultracentrifugation, SDS-polyacrylamide gel electrophoresis, and the number of peptides produced by CNBr cleavage. The number of NADP binding sites was determined to be one per 25,500 dalton unit.


Pathologic changes of skin and hair in ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome.
Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome is a rare disorder of hair, skin, nails, and dentition caused by mutations in the p63 gene. Pathologic changes of skin and hair in AEC syndrome have previously been described in isolated case reports. Biopsies of normal and lesional skin from 19 patients with AEC syndrome were examined by light microscopy. Hair samples from 18 patients were examined by light and scanning electron microscopy. Histopathologic changes identified within the skin biopsies from clinically unaffected skin include mild atrophy, focal orthokeratosis, and mild superficial perivascular lymphocytic dermatitis. Scattered melanophages in the superficial and deep dermis likely reflect post-inflammatory change. One patient with a unilateral eruption of monomorphic papulopustules on the chest and shoulder demonstrated an acneiform intraepidermal pustule. Examination of the hair shafts revealed atrophy and loss of melanin pigment in some of the patients. Structural abnormalities included pili torti, pili trianguli et canaliculi, and irregular indentation and shallow grooves. Skin and hair findings in AEC syndrome were found to be generally similar to those described in other ectodermal dysplasia syndromes and corroborates the few prior descriptions in AEC syndrome specifically.


[Multiple organ failure in patients after surgical removal of insulinoma].
There were 96 patients with various nonpurulent pancreatic gland diseases examined. Postoperative disorders of function of myocardium, liver, kidneys, hormonal-metabolic state, inflammatory and reactive processes in blood, mostly pronounced after partial pancreatic resection conduction, were observed in 49 patients with organic hyperinsulinism having a background of initial changes in homeostasis.


The Ecology of Acidophilic Microorganisms in the Corroding Concrete Sewer Environment.
Concrete corrosion is one of the most significant problems affecting valuable sewer infrastructure on a global scale. This problem occurs in the aerobic zone of the sewer, where a layer of surface corrosion develops on the exposed concrete and the surface pH is typically lowered from around 11-10 (pristine concrete) to pH 2-4. Acidophilic microorganisms become established as biofilms within the concrete corrosion layer and enhance the loss of concrete mass. Until recently, the acidophilic community was considered to comprise relatively few species of microorganisms, however, the biodiversity of the corrosion community is now recognized as being extensive and varying from different sewer environmental conditions. The diversity of acidophiles in the corrosion communities includes chemolithoautotrophs, chemolithoheterotrophs, and chemoorganoheterotrophs. The activity of these microorganisms is strongly affected by H2S levels in the sewer gas phase, although CO2, organic matter, and iron in the corrosion layer influence this acidic ecosystem. This paper briefly presents the conditions within the sewer that lead to the development of concrete corrosion in that environment. The review focuses on the acidophilic microorganisms detected in sewer corrosion environments, and then summarizes their proposed functions and physiology, especially in relation to the corrosion process. To our knowledge, this is the first review of acidophilic corrosion microbial communities, in which, the ecology and the environmental conditions (when available) are considered. Ecological studies of sewer corrosion are limited, however, where possible, we summarize the important metabolic functions of the different acidophilic species detected in sewer concrete corrosion layers. It is evident that microbial functions in the acidic sewer corrosion environment can be linked to those occurring in the analogous acidic environments of acid mine drainage and bioleaching.


The role of GABAB receptors in human reinforcement learning.
Behavioral evidence from human studies suggests that the γ-aminobutyric acid type B receptor (GABAB receptor) agonist baclofen modulates reinforcement learning and reduces craving in patients with addiction spectrum disorders. However, in contrast to the well established role of dopamine in reinforcement learning, the mechanisms by which the GABAB receptor influences reinforcement learning in humans remain completely unknown. To further elucidate this issue, a cross-over, double-blind, placebo-controlled study was performed in healthy human subjects (N=15) to test the effects of baclofen (20 and 50mg p.o.) on probabilistic reinforcement learning. Outcomes were the feedback-induced P2 component of the event-related potential, the feedback-related negativity, and the P300 component of the event-related potential. Baclofen produced a reduction of P2 amplitude over the course of the experiment, but did not modulate the feedback-related negativity. Furthermore, there was a trend towards increased learning after baclofen administration relative to placebo over the course of the experiment. The present results extend previous theories of reinforcement learning, which focus on the importance of mesolimbic dopamine signaling, and indicate that stimulation of cortical GABAB receptors in a fronto-parietal network leads to better attentional allocation in reinforcement learning. This observation is a first step in our understanding of how baclofen may improve reinforcement learning in healthy subjects. Further studies with bigger sample sizes are needed to corroborate this conclusion and furthermore, test this effect in patients with addiction spectrum disorder.


[Effects of green tea extract on expression of human papillomavirus type 16 oncoproteins-induced hypoxia-inducible factor-1alpha and vascular endothelial growth factor in human cervical carcinoma cells].
To investigate the effects of green tea extract (GTE) and its major component (-)-epigallocatechin-3-gallate (EGCG) on the human papillomavirus (HPV) type 16 oncoproteins (E6 and E7)-induced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) in human cervical carcinoma cells. Human cervical carcinoma cells of the line C-33A were divided to 4 groups to be transiently transfected with the plasmid HA-pSG5-HPV-16E6 containing the HPV type 16 oncoprotein E6, HA-pSG5-HPV-16 E7, or empty plasmid HA-pSG5, or just exposed to the transfection reagent Lipofectamine 2000 as mock transfection control group. Western blotting and ELISA were used to detect the protein expression of HIF-1alpha and the protein expression of VEGF 18, 24, and 48 h after the transfection. Twenty-four hours after the transfection, the transfected-cells were treated with GTE (40 microg/ml) or EGCG (50 micromol/L) for 8, 16, and 24 h respectively, or treated with GTE of the concentrations of 20, 40, and 80 microg/ml or EGCG of the concentrations of 25, 50, and 100 micromol/L respectively for 16 h. The HIF-1alpha and VEGF protein levels were analyzed by Western blotting and ELISA respectively and the HIF-1alpha and VEGF mRNA levels were determined with real-time PCR. Twenty-four hours after transfection, the HIF-1alpha protein expression of the 16E6 and 16E7 groups were significantly decreased, and the VEGF protein levels of the 16E6 and 16E7 groups were (870+/-66) and (1487+/-51) pg/ml respectively, both significantly higher than that of the empty plasmid group [(366+/-65) pg/ml, both P<0.01]. Treated by 40 microg/ml of GTE or 50 micromol/L of EGCG for 16 h, (1) the HIF-1alpha protein levels of the 16E6 and 16E7 groups were significantly decreased; (2) the VEGF protein levels of the 16E6 group were (476+/-34) and (477+/-65) pg/ml respectively, and the VEGF mRNA levels of the 16E6 group were 1.208+/-0.196 and 1.174+/-0.208 respectively, all significantly lower than those of the untreated group [(870+/-66) pg/ml and 1.805+/-0.081 respectively, all P<0.01]; and (3) the VEGF protein levels of the 16E7 group were (649+/-55) and (514+/-37) pg/ml respectively, and the VEGF mRNA levels of the 16E7 group were 1.442+/-0.136 and 1.399+/-0.064 respectively, all significantly lower than those of untreated group [(1487+/-51) pg/ml and 2.123+/-0.120 respectively, all P<0.01]. The 80 microg/ml of GTE or 100 micromol/L of EGCG showed much stronger effects on the inhibition of VEGF protein expression than 40 microg/ml of GTE or 50 micromol/L of EGCG (both P<0.01). GTE and EGCG can remarkably inhibit the HPV-16 oncoproteins-induced expression of HIF-1alpha protein, and VEGF protein and mRNA in human cervical carcinoma cells. Moreover, GTE and EGCG decrease the VEGF protein expression dose-dependently.


[Ovarian cancer and borderline tumors].
Long-term trends in the incidence, prognosis, and mortality of patients with ovarian cancer and borderline tumours in Norway were examined based on data from the population-based Cancer Registry of Norway. The incidence of ovarian cancer rose continuously from the mid-1950s to the mid-1980s. There was also an increasing trend in the incidence of borderline tumours from the early 1970s to the early 1990s. The prognosis for patients with ovarian cancer has improved since the 1950s. In 1989-93 the five-year relative survival rate was 37%. The prognosis for patients with borderline tumours was very favourable, with a five-year relative survival rate of 93% (1970-93). The mortality from ovarian cancer has been almost constant since the 1960s.


Emotional responses to a romantic partner's imaginary rejection: the roles of attachment anxiety, covert narcissism, and self-evaluation.
These studies tested the associations between responses to an induced imaginary romantic rejection and individual differences on dimensions of attachment and covert narcissism. In Study 1 (N=125), we examined the associations between attachment dimensions and emotional responses to a vignette depicting a scenario of romantic rejection, as measured by self-reported negative mood states, expressions of anger, somatic symptoms, and self-evaluation. Higher scores on attachment anxiety, but not on attachment avoidance, were associated with stronger reactions to the induced rejection. Moreover, decreased self-evaluation scores (self-esteem and pride) were found to mediate these associations. In Study 2 (N=88), the relative contributions of covert narcissism and attachment anxiety to the emotional responses to romantic rejection were explored. Higher scores on covert narcissism were associated with stronger reactions to the induced rejection. Moreover, covert narcissism seemed to constitute a specific aspect of attachment anxiety.


GeneMANIA update 2018.
GeneMANIA (http://genemania.org) is a flexible user-friendly web site for generating hypotheses about gene function, analyzing gene lists and prioritizing genes for functional assays. Given a query gene list, GeneMANIA finds functionally similar genes using a wealth of genomics and proteomics data. In this mode, it weights each functional genomic dataset according to its predictive value for the query. Another use of GeneMANIA is gene function prediction. Given a single query gene, GeneMANIA finds genes likely to share function with it based on their interactions with it. Enriched Gene Ontology categories among this set can point to the function of the gene. Nine organisms are currently supported (Arabidopsis thaliana, Caenorhabditis elegans, Danio rerio, Drosophila melanogaster, Escherichia coli, Homo sapiens, Mus musculus, Rattus norvegicus and Saccharomyces cerevisiae). Hundreds of data sets and hundreds of millions of interactions have been collected from GEO, BioGRID, IRefIndex and I2D, as well as organism-specific functional genomics data sets. Users can customize their search by selecting specific data sets to query and by uploading their own data sets to analyze. We have recently updated the user interface to GeneMANIA to make it more intuitive and make more efficient use of visual space. GeneMANIA can now be used effectively on a variety of devices.


Impact of High-Intensity Interval Training on Body Composition and Depressive Symptoms in Adults under Home Confinement.
The home confinement derived from the COVID-19 pandemic has led to drastic changes in people's habits. This situation has influenced their eating, rest, physical activity and socialization patterns, triggering changes in their mental stability. It was demonstrated that physical activity is beneficial for people's physical and mental health. By its moderate volume and requiring little space or material, high-intensity interval training (HIIT) could prove to be a valid alternative in a situation of confinement. The aim of the present study was to observe the impact of an 8-week HIIT protocol on the body composition and the depressive symptoms of adults in strict home confinement. A total of 21 healthy adults, both male and female, (35.4 ± 5.6 years old; 70.50 ± 12.1 kg; 171 ± 10 cm) were divided into an experimental group (EG, n = 11) who carried out an 8-week Tabata protocol, based upon calisthenic exercises with their own weight in their homes, and a control group (CG, n = 10) who did not carry out any systematic physical activity over the same period. Following the intervention, the EG experienced a significant reduction in percentage (t = 3.86, d = 0.57, p < 0.05) and in kg (t = 4.62, d = 0.29, p < 0.05) of body fat mass (BFM) and body fat mass index (BFMI) (t = 4.61, d = 0.31, p < 0.05), as well as a reduction in depressive symptoms (t = 6.48, d = 1.3, p < 0.05). These results indicate that HIIT is a potential public health tool that could possibly be prescribed to the population in case of future situations of home confinement.


N-linked glycosylation protects gammaretroviruses against deamination by APOBEC3 proteins.
Retroviruses are pathogens with rapid infection cycles that can be a source of disease, genome instability, and tumor development in their hosts. Host intrinsic restriction factors, such as APOBEC3 (A3) proteins, are constitutively expressed and dedicated to interfering with the replication cycle of retroviruses. To survive, propagate, and persist, retroviruses must counteract these restriction factors, often by way of virus genome-encoded accessory proteins. Glycosylated Gag, also called glycosylated Pr80 Gag (gPr80), is a gammaretrovirus genome-encoded protein that inhibits the antiretroviral activity of mouse A3 (mA3). Here we show that gPr80 exerts two distinct inhibitory effects on mA3: one that antagonizes deamination-independent restriction and another one that inhibits its deaminase activity. More specifically, we find that the number of N-glycosylated residues in gPr80 inversely correlates with the sensitivity of a gammaretrovirus to deamination by mouse A3 and also, surprisingly, by human A3G. Finally, our work highlights that retroviruses which have successfully integrated into the mouse germ line generally express a gPr80 with fewer glycosylated sites than exogenous retroviruses. This observation supports the suggestion that modulation of A3 deamination intensity could be a desirable attribute for retroviruses to increase genetic diversification and avoid immune detection. Overall, we present here the first description of how gammaretroviruses employ posttranslational modification to antagonize and modulate the activity of a host genome-encoded retroviral restriction factor. APOBEC3 proteins are host factors that have a major role in protecting humans and other mammals against retroviruses. These enzymes hinder their replication and intensely mutate their DNA, thereby inactivating viral progeny and the spread of infection. Here we describe a newly recognized way in which some retroviruses protect themselves against the mutator activity of APOBEC3 proteins. We show that gammaretroviruses expressing an accessory protein called glycosylated Gag, or gPr80, use the host's posttranslational machinery and, more specifically, N-linked glycosylation as a way to modulate their sensitivity to mutations by APOBEC3 proteins. By carefully controlling the amount of mutations caused by APOBEC3 proteins, gammaretroviruses can find a balance that helps them evolve and persist.


[Involvement of the central nervous system in disseminated tuberculosis].
Four weeks after starting tuberculostatic treatment (with isoniazid, rifampicin, streptomycin and pyrazinamide) a 21-year-old man with pulmonary tuberculosis developed symptoms of a radiculomyelopathy as well as mild renal failure. After isoniazid and streptomycin had been discontinued and ethambutol and high doses of vitamin B6 had been added all signs and symptoms improved. However, 4 weeks later tuberculous meningitis occurred which at first seemed to respond to administration of 5 antituberculosis drugs and dexamethasone. But 3 weeks later the patient sustained a partial hemiparesis. Its cause was proven to be a tuberculoma in the region of the brainstem. During further administration of tuberculostatic drugs and glucocorticoids the symptoms gradually receded over 8 months. A 54-year-old man with pulmonary tuberculosis developed cranial nerve pareses and symptoms of cerebellar involvement (trunk ataxia, intention tremor, dysdiadochokinesia) 3 weeks after starting tuberculostatic treatment. Computed tomography revealed multiple intracerebral tuberculomas which gradually shrank with continuation of the tuberculostatic treatment plus glucocorticoids. These two case reports illustrate that in tuberculosis involvement of the CNS can express itself clinically through complex symptoms, sometimes even after the start of tuberculostatic treatment.


1,2-Insertion reactions of alkynes into Ge-C bonds of arylbromogermylene.
1,2-Insertion reactions of alkynes into the Ge-C bonds in dibromodigermenes afford stable crystalline bromovinylgermylenes. In contrast to previously reported Lewis-base-supported vinylgermylenes, the bromovinylgermylene obtained from reaction of the bromogermylene with 3-hexyne via such an 1,2-insertion is a donor-free monomer. A feasible reaction mechanism, proposed on the basis of the observed experimental results in combination with theoretical calculations, suggests that the [1+2]-cycloadduct and the insertion product are the kinetic and thermodynamic product, respectively.


Effects of a constructed wetland and pond system upon shallow groundwater quality.
Constructed wetland (CW) and constructed pond (CP) are commonly utilized for removal of excess nutrients and certain pollutants from stormwater. This study characterized shallow groundwater quality for pre- and post-CW and CP system conditions using data from monitoring wells. Results showed that the average concentrations of groundwater phosphorus (P) decreased from pre-CW to post-CW but increased from pre-CP to post-CP. The average concentrations of groundwater total Kjeldahl nitrogen and ammonium (NH(4)(+)) increased from pre-CW (or CP) to post-CW (or CP), whereas the average concentrations of groundwater arsenic (As), chromium, nickel, and zinc (Zn) decreased from pre-CW to post-CW regardless of the well locations. Variations of groundwater cadmium, copper, and Zn concentrations were larger in pre-CP than in post-CP and had a tendency to decrease from pre-CP to post-CP. In general, the average concentrations of groundwater aluminum and manganese decreased and of groundwater calcium, iron, magnesium, and sodium increased from pre-CP to post-CP. The average values of water levels (depth from the ground surface), redox potential, and conductance decreased and of chloride and sulfate (SO(4)(-2)) increased after the wetland and pond were constructed regardless of the well locations. Results further revealed that there were significant differences (α = 0.05) between the pre- and post-CW (or CP) for redox potential, water level, and As. This study suggests that the CW-CP system had discernible effects on some of the shallow groundwater quality constituents. This information is very useful for fully estimating overall performance of stormwater treatment with the CW-CP system.


Crosstalk between the Akt/mTORC1 and NF-κB signaling pathways promotes hypoxia-induced pulmonary hypertension by increasing DPP4 expression in PASMCs.
Abnormal wound healing by pulmonary artery smooth muscle cells (PASMCs) promotes vascular remodeling in hypoxia-induced pulmonary hypertension (HPH). Increasing evidence shows that both the mammalian target of rapamycin complex 1 (mTORC1) and nuclear factor-kappa B (NF-κB) are involved in the development of HPH. In this study, we explored the crosstalk between mTORC1 and NF-κB in PASMCs cultured under hypoxic condition and in a rat model of hypoxia-induced pulmonary hypertension (HPH). We showed that hypoxia promoted wound healing of PASMCs, which was dose-dependently blocked by the mTORC1 inhibitor rapamycin (5-20 nM). In PASMCs, hypoxia activated mTORC1, which in turn promoted the phosphorylation of NF-κB. Molecular docking revealed that mTOR interacted with IκB kinases (IKKs) and that was validated by immunoprecipitation. In vitro kinase assays and mass spectrometry demonstrated that mTOR phosphorylated IKKα and IKKβ separately. Inhibition of mTORC1 decreased the level of phosphorylated IKKα/β, thus reducing the phosphorylation and transcriptional activity of NF-κB. Bioinformatics study revealed that dipeptidyl peptidase-4 (DPP4) was a target gene of NF-κB; DPP4 inhibitor, sitagliptin (10-500 μM) effectively inhibited the abnormal wound healing of PASMCs under hypoxic condition. In the rat model of HPH, we showed that NF-κB activation (at 3 weeks) was preceded by mTOR signaling activation (after 1 or 2 weeks) in lungs, and administration of sitagliptin (1-5 mg/kg every day, ig) produced preventive effects against the development of HPH. In conclusion, hypoxia activates the crosstalk between mTORC1 and NF-κB, and increased DPP4 expression in PASMCs that leads to vascular remodeling. Sitagliptin, a DPP4 inhibitor, exerts preventive effect against HPH.


Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients: A retrospective observational study.
The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.


Angiocrine Signaling in Sinusoidal Health and Disease.
Liver sinusoidal endothelial cells (LSECs) are key players in maintaining hepatic homeostasis. They also play crucial roles during liver injury by communicating with liver cell types as well as immune cells and promoting portal hypertension, fibrosis, and inflammation. Cutting-edge technology, such as single cell and spatial transcriptomics, have revealed the existence of distinct LSEC subpopulations with a clear zonation in the liver. The signals released by LSECs are commonly called "angiocrine signaling." In this review, we summarize the role of angiocrine signaling in health and disease, including zonation in healthy liver, regeneration, fibrosis, portal hypertension, nonalcoholic fatty liver disease, alcohol-associated liver disease, aging, drug-induced liver injury, and ischemia/reperfusion, as well as potential therapeutic advances. In conclusion, sinusoidal endotheliopathy is recognized in liver disease and promising preclinical studies are paving the path toward LSEC-specific pharmacotherapies.


Spinal cord astrocytoma presenting as torticollis and scoliosis.
To illustrate the importance of a careful differential diagnosis in children presenting with torticollis. A 14-yr-old boy presented with a 6-month history of neck pain, torticollis and increasing neurological deficit. Past physiotherapy and chiropractic treatment had not helped. A myelogram and MRI scan revealed a large intramedullary lesion. He was treated by laminectomy with partial excision of the lesion, followed by radiotherapy. Pathology confirmed the diagnosis of astrocytoma. The patient developed postlaminectomy instability and required spinal fusion. The differential diagnosis of torticollis in children is extensive and should always include spinal tumor.


Urokinase plasminogen receptor and the fibrinolytic complex play a role in nerve repair after nerve crush in mice, and in human neuropathies.
Remodeling of extracellular matrix (ECM) is a critical step in peripheral nerve regeneration. In fact, in human neuropathies, endoneurial ECM enriched in fibrin and vitronectin associates with poor regeneration and worse clinical prognosis. Accordingly in animal models, modification of the fibrinolytic complex activity has profound effects on nerve regeneration: high fibrinolytic activity and low levels of fibrin correlate with better nerve regeneration. The urokinase plasminogen receptor (uPAR) is a major component of the fibrinolytic complex, and binding to urokinase plasminogen activator (uPA) promotes fibrinolysis and cell movement. uPAR is expressed in peripheral nerves, however, little is known on its potential function on nerve development and regeneration. Thus, we investigated uPAR null mice and observed that uPAR is dispensable for nerve development, whereas, loss of uPAR affects nerve regeneration. uPAR null mice showed reduced nerve repair after sciatic nerve crush. This was a consequence of reduced fibrinolytic activity and increased deposition of endoneurial fibrin and vitronectin. Exogenous fibrinolysis in uPAR null mice rescued nerve repair after sciatic nerve crush. Finally, we measured the fibrinolytic activity in sural nerve biopsies from patients with peripheral neuropathies. We showed that neuropathies with defective regeneration had reduced fibrinolytic activity. On the contrary, neuropathies with signs of active regeneration displayed higher fibrinolytic activity. Overall, our results suggest that enforced fibrinolysis may facilitate regeneration and outcome of peripheral neuropathies.


Quality-improvement strategies for the management of hypertension in chronic kidney disease in primary care: a systematic review.
Chronic kidney disease (CKD) is a relatively recently recognised condition. People with CKD are much more likely to suffer from cardiovascular events than progress to established renal failure. Controlling systolic blood pressure should slow the progression of disease and reduce mortality and morbidity. However, no systematic review has been conducted to explore the effectiveness of quality-improvement interventions to lower blood pressure in people with CKD. To assess the effectiveness of quality-improvement interventions to reduce systolic blood pressure in people with CKD in primary care, in order to reduce cardiovascular risk and slow the progression of renal disease. Papers were identified from the trial data bases of the Cochrane Effective Practice and Organisation of Care Group (EPOC) and Cochrane renal groups. In a three-round process, at least two investigators read the papers independently. Studies were initially excluded based on their abstracts, if these were not relevant to primary care. Next, full papers were read, and again excluded on relevance. Quantitative and, where this was not possible, qualitative analyses of the findings were performed. The selected studies were usually carried out on high-risk populations including ethnic minorities. The interventions were most often led by nurses or pharmacists. Three randomised trials showed a combined effect of a reduction in systolic blood pressure of 10.50 mmHg (95% confidence interval [CI] = 5.34 to 18.41 mmHg). One non-randomised study showed a reduction in systolic blood pressure of 9.30 mmHg (95% CI = 3.01 to 15.58 mmHg). Quality-improvement interventions can be effective in lowing blood pressure, and potentially in reducing cardiovascular risk and slowing progression in CKD. Trials are needed in low-risk populations to see if the same improvements can be achieved.


Assembly of human C-terminal binding protein (CtBP) into tetramers.
C-terminal binding protein 1 (CtBP1) and CtBP2 are transcriptional coregulators that repress numerous cellular processes, such as apoptosis, by binding transcription factors and recruiting chromatin-remodeling enzymes to gene promoters. The NAD(H)-linked oligomerization of human CtBP is coupled to its co-transcriptional activity, which is implicated in cancer progression. However, the biologically relevant level of CtBP assembly has not been firmly established; nor has the stereochemical arrangement of the subunits above that of a dimer. Here, multi-angle light scattering (MALS) data established the NAD+- and NADH-dependent assembly of CtBP1 and CtBP2 into tetramers. An examination of subunit interactions within CtBP1 and CtBP2 crystal lattices revealed that both share a very similar tetrameric arrangement resulting from assembly of two dimeric pairs, with specific interactions probably being sensitive to NAD(H) binding. Creating a series of mutants of both CtBP1 and CtBP2, we tested the hypothesis that the crystallographically observed interdimer pairing stabilizes the solution tetramer. MALS data confirmed that these mutants disrupt both CtBP1 and CtBP2 tetramers, with the dimer generally remaining intact, providing the first stereochemical models for tetrameric assemblies of CtBP1 and CtBP2. The crystal structure of a subtle destabilizing mutant suggested that small structural perturbations of the hinge region linking the substrate- and NAD-binding domains are sufficient to weaken the CtBP1 tetramer. These results strongly suggest that the tetramer is important in CtBP function, and the series of CtBP mutants reported here can be used to investigate the physiological role of the tetramer.


Ablation in Persistent Atrial Fibrillation Using Stochastic Trajectory Analysis of Ranked Signals (STAR) Mapping Method.
The aim of this study was to demonstrate that a stochastic vector-based mapping approach could guide ablation of atrial fibrillation (AF) drivers as evidenced by ablation response and long-term follow-up outcomes. The optimal method for mapping and ablation of AF drivers is yet to be defined. Patients undergoing persistent AF ablation were recruited. Patients underwent pulmonary vein isolation (PVI) with further ablation guided by the stochastic trajectory analysis of ranked signals (STAR) mapping method. The proportion of the time an electrode's activation was seen to precede its neighboring electrodes activation was used to determine early sites of activation (ESA). A positive ablation response at ESA was defined as AF termination or cycle length slowing of ≥30 ms. Clinical outcome was defined as recurrence of AF/atrial tachycardia (AT) during a follow-up of 12 months. Thirty-five patients were included (AF duration of 14.4 ± 5.3 months). After PVI, an average of 2.6 ± 0.8 ESA were ablated per patient with study-defined ablation response achieved in all patients. Of the 86 STAR maps created post-PVI, the same ESA was identified on 73.8 ± 26.1% of maps. ESA that resulted in AF termination were more likely to be identified on both pre- and post-PVI maps than those associated with cycle length slowing (23 of 24 vs. 16 of 49; p < 0.001). During a follow-up of 18.5 ± 3.7 months, 28 (80%) patients were free from AF/AT. The ablation response at ESA suggests they may be drivers of AF. Ablation guided by STAR mapping produced a favorable clinical outcome and warrants testing through a randomized controlled trial. (Identification, Electro-mechanical Characterisation and Ablation of Driver Regions in Persistent Atrial Fibrillation [STAR MAPPING]; NCT02950844).


Molecular cloning of two human cardiac gap junction proteins, connexin40 and connexin45.
Intercellular coupling of cardiac myocytes through gap junction channels facilitates normal cardiac impulse conduction. Multiple gap junction sequences (connexins) have been previously identified in mammalian and avian heart, but only one, connexin43 (Cx43), has been identified in the human heart. We used the polymerase chain reaction and genomic cloning to isolate DNA encoding the gap junction proteins human connexin40 (Cx40) and connexin45 (Cx45). Northern blots showed that specific probes for Cx43, Cx40 and Cx45 all hybridize to distinct mRNAs in human ventricular RNA. Immunohistochemistry with connexin-specific antibodies confirmed that Cx40, Cx43, and Cx45 all localized to intercalated disk regions in frozen sections of human left ventricle. The presence of multiple connexins in human ventricle may contribute to divergent mechanisms of regulation of cardiac conduction.


Realistic expectations: investing in organizational capacity building for chronic disease prevention.
This article presents findings that explore investment in organizational capacity building for chronic disease prevention. Specifically, this analysis examines variation in investment inputs, intervention outputs, and capacity changes to inform expectations of health-promotion capacity-building investment. This multiple case study involving both qualitative and quantitative data is based on seven provincial dissemination projects involved in the Canadian Heart Health Initiative. Data on investment, number, and type of capacity-building activities and capacity changes come from a questionnaire, key informant interviews, and project report analysis. Quantitative data were analyzed descriptively and for trends, while qualitative data were analyzed thematically. Per capita investments in capacity building ranged from a low of $0.21 in Ontario to $167.41 in Prince Edward Island. Multiple, tailored capacity-building interventions were used in each project. Mostly positive but modest changes were observed in at least five dimensions of capacity in all but one project. These findings reveal that capacity building for chronic disease prevention requires a long-term investment and is context specific. Even limited investment can produce interventions that appear to positively influence capacity for chronic disease prevention. The findings also suggest an urgent need to expand surveillance to include indicators of capacity-building investments and interventions to allow policy makers to make more informed decisions about investments in public health.


Effects of chronic chromium(vi) exposure on blood element homeostasis: an epidemiological study.
One hundred chromate production workers chronically exposed to low-level of hexavalent chromium [Cr(vi)] and eighty healthy individuals free from Cr exposure were recruited to the study. Personal sampling of airborne Cr was conducted and Cr content was quantified by Flame Atomic Absorption Spectrometry (FAAS). At the end of the sampling shift, blood samples were collected and element concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS) for Cr, Cd, Cu, Mo and Se and inductively coupled plasma atomic emission spectrometry (ICP-AES) for Ca, Fe, Mg and Zn. According to our results, 90% of the chromate production workers were exposed to airborne Cr in a concentration lower than 50 μg m(-3), which is the threshold limit value recommended by the American Conference of Governmental Industrial Hygienists and Chinese Ministry of Health. After Cr(vi) exposure, a significant increase in blood Cr, Cd, Fe, Mg, Mo, Se and Zn concentrations was observed, as well as a significant decrease in Ca concentration. A decrease in blood Cu was only observed among female workers. Blood Cr concentrations of the exposed workers (median = 15.68 ng mL(-1)) was four times higher than that of the controls (median = 3.03 ng mL(-1)), and significantly correlated with airborne Cr (r = 0.568, P<0.001). In addition, the inter-element correlations exhibited significant differences between the two groups. Our findings of the related health effects suggested that the underlying mechanisms of chronic Cr(vi) exposure on blood element homeostasis might be partly explained by oxidative stress in the body, dysfunction of Fe metabolism and renal injury.


Generalized joint laxity and multidirectional instability of the shoulder.
Generalized joint laxity and shoulder instability are common conditions that exhibit a wide spectrum of different clinical forms and may coexist in the same patient. Generalized joint laxity can be congenital or acquired. It is fundamental to distinguish laxity from instability. Laxity is a physiological condition that may predispose to the development of shoulder instability. A high prevalence of generalized joint laxity has been identified in patients with multidirectional instability of the shoulder. Multidirectional instability is defined as symptomatic instability in two or more directions. The diagnosis and treatment of this condition are still challenging because of complexities in its classification and etiology. These complexities are compounded when multidirectional instability and laxity exist in the same patient. With an improved understanding of the clinical symptoms and physical examination findings, a successful strategy for conservative and/or surgical treatments can be developed. Conservative treatment is the first-line option. If it fails, different surgical options are available. Historically, open capsular shift has been considered the gold standard in the surgical management of these patients. Nowadays, advanced arthroscopic techniques offer several advantages over traditional open approaches and have shown similar outcomes. The correct approach to the management of failed stabilization procedures has not been yet defined.


Physicochemical Properties and Intestinal Health Promoting Water-Insoluble Fiber Enriched Fraction Prepared from Blanched Vegetable Soybean Pod Hulls.
Different methods can be used to change the fiber compositions of food, and they consequently affect the physicochemical properties and physiological activities. The present study compared the effects of a blanching treatment on the physicochemical properties of water-insoluble fiber enriched fraction (WIFF) from three varieties of vegetable soybean pod hulls (tea vegetable soybean pod hull, TVSPH; black vegetable soybean pod hull, BVSPH; 305 vegetable soybean pod hulls, 305VSPH) and evaluated their effects on intestinal health in hamsters. Blanching may increase the soluble dietary fiber (SDF) content of WIFF in the 305VSPH variety by solubilizing cell wall components and releasing water-soluble sugars. Thus, the WIFF in the 305VSPH variety after blanching may be composed of cellulose and pectic substances. The WIFF of the blanched 305VSPH (B-305VSPH) variety exhibited the highest physicochemical properties, such as a water-retention capacity (11.7 g/g), oil-holding capacity (9.34 g/g), swelling property (10.8 mL/g), solubility (12.2%), and cation-exchange capacity (221 meq/kg), of the three varieties examined. The supplementation of B-305VSPH WIFF in the diet resulted in significantly (p < 0.05) lower cecal and fecal ammonia; activities of fecal β-d-glucosidase, β-d-glucuronidase, mucinase, and urease; as well as higher cecal total short-chain fatty acids relative to other diets. In addition, microbial analysis suggested that fecal bifidobacteria growth was enhanced by the consumption of B-305VSPH WIFF. Therefore, B-305VSPH WIFF may be applicable as a potential functional ingredient in the food industry for the improvement of intestinal health.


Blockade of B2 receptors attenuates the responses of group III afferents to static contraction.
Recent evidence has been presented demonstrating that group III mechanoreceptors comprise an important part of the sensory arm of the exercise pressor reflex, which in turn functions to increase arterial blood flow to contracting skeletal muscles. Although group III afferents are stimulated by mechanical distortion of their receptive fields, they are also stimulated by bradykinin, which is produced by skeletal muscle when it contracts. Moreover, blockade of B (bradykinin)2 receptors has been shown to decrease the magnitude of the exercise pressor reflex. Nevertheless, the effect of blockade of B2 receptors on responses of group III afferents to contraction is not known. We therefore determined the effect of B2 receptor blockade with HOE 140 (40μg/kg) on the responses to both static and intermittent contraction of group III afferents with endings in the triceps surae muscle of decerebrated unanesthetized cats. We found that HOE 140 significantly attenuated (P=0.04) the responses of 14 group III afferents to static contraction, but did not significantly attenuate (P=0.16) the responses of 16 group III afferents to intermittent contraction. The attenuation induced by HOE 140 was present throughout the static contraction period, and led us to speculate that blockade of B2 receptors on the endings of group III afferents decreased their sensitivity to mechanical events occurring in the working muscles.


Rat lung hyper-reactivity to stress.
Rats have been used frequently as a model for determining the pulmonary response to various stressful situations. It has been shown in the literature that rat lungs are remarkably sensitive to factors which result in the development of gross pulmonary injury, such as stress from exposure to hyperbaric oxygen. Similarly, a high degree of pulmonary reactivity was found in rats after administration of various CNS, convulsants and also exposure to mechanical vibration. The present study was confined to a determination of the gross pulmonary response of rats exposed to mechanical CNS traumatization compared to that of 10 other laboratory species. The frequency and severity of pulmonary injury from CNS traumatization, as indicated by lung weight/body weight ratios and gross appearance, was very striking in the traumatized rats, but we found little or no change in cats, dogs, rabbits and guinea pigs, in Rhesus, squirrel, vervet, and cynomolgus monkeys or in baboons and chimpanzees. Previous studies showed that the gross pulmonary injury from this mechanical head injury in rats, as well as from hyperbaric oxygen exposure, vibration, and CNS convulsants, was ameliorated by the prior administration of various sympathetic blocking agents. The results from the present comparative study tend to suggest that rat lungs are hyper-reactive to this stress.


The Acceptance, Usability, and Utility of a Web Portal for Back Pain as Recommended by Primary Care Physicians: Qualitative Interview Study With Patients.
An ever-increasing number of patients seek health information via the internet. However, there is an overabundance of differing, often low-quality information available, while a lack of health literacy makes it difficult for patients to understand and assess the quality and trustworthiness of the information at hand. The web portal tala-med was thus conceived as an evidence-based, up-to-date, and trustworthy information resource for lower back pain (LBP), which could be used by primary care physicians (PCPs) and patients during and following consultations for LBP. The current evidence demonstrates that patients with LBP could benefit from web portals. However, the use of such portals by patients remains low, thus limiting their effectiveness. Therefore, it is important to explore the factors that promote or hinder the use of web portals and investigate how patients perceive their usability and utility. In this study, we investigated the acceptance, usability, and utility of the web portal tala-med from the patient perspective. This qualitative study was based on telephone interviews with patients who had access to the web portal tala-med from their PCP. We used a semistructured interview guide that consisted of questions about the consultation in which patients were introduced to tala-med, in addition to questions regarding patient perceptions, experiences, and utilization of tala-med. The interviews were recorded, transcribed, and analyzed through framework analysis. A total of 32 half-hour interviews were conducted with 16 female and 16 male patients with LBP. We identified 5 themes of interest: the use of tala-med by PCPs during the consultation, the use of tala-med by patients, its usability, added values derived from its use, and the resultant effects of using tala-med. PCPs used tala-med as an additional information resource for their patients and recommended the exercises. The patients appreciated these exercises and were willing to use tala-med at home. We also identified factors that promoted or hindered the use of tala-med by patients. Most patients rated tala-med positively and considered it a clear, comprehensible, trustworthy, and practical resource. In particular, the trustworthiness of tala-med was seen as an advantage over other information resources. The possibilities offered by tala-med to recap and reflect on the contents of consultations in a time-flexible and independent manner was perceived as an added value to the PCP consultation. Tala-med was well accepted by patients and appeared to be well suited to being used as an add-on to PCP consultations. Patient perception also supports its usability and utility. Tala-med may therefore enrich consultations and assist patients who would otherwise be unable to find good-quality web-based health information on LBP. In addition, our findings support the future development of digital health platforms and their successful use as a supplement to PCP consultations. RR2-10.1186/s12875-019-0925-8.


Assessment of Antioxidant Effect of Beta-Glucan on the Whole Blood Oxidative DNA Damage with the Comet Assay in Colorectal Cancer.
The present study aims to evaluate the antioxidant effect of beta-glucan on oxidative DNA damage by comet assay. A total of 19 adult females and males diagnosed with stage 3-4 colorectal cancer and a control group of 20 age-matched healthy subjects were enrolled in the study. Blood samples of the participants were analyzed using Comet Assay for the parameters of DNA damage. Significantly increased DNA damage was observed in patients versus the control group as indicated by greater values of tail moment, tail percent DNA and tail length. Following incubation with β-glucan, a substantial reduction was found in the aforementioned parameters of DNA damage. Comet assay revealed significant levels of endogenous DNA damage in patients as shown by remarkable increases in the tail moment, the percentage of DNA in the tail and the tail length values, in comparison with the control group. Following treatment of fresh whole blood with β-glucan incubation, DNA damages were significantly reduced, but lower values were observed after β-glucan incubation in the patient group versus control group. β-Glucan was found to reduce DNA damage substantially in colorectal cancer patients and show antimutagenic effects. Our results suggested that dietary β-glucan intake might be important in the genesis of colorectal cancer tumors.


Neobacillus rhizosphaerae sp. nov., isolated from the rhizosphere, and reclassification of Bacillus dielmonensis as Neobacillus dielmonensis comb. nov.
A Gram-stain-positive, facultative anaerobic endospore-forming bacterium, which originated from roots/rhizosphere of maize (Zea mays), was investigated for its taxonomic position. On the basis of 16S rRNA gene sequence similarities, strain JJ-3T was grouped together with Neobacillus species showing the highest similarities to Neobacillus bataviensis (98.8 %) and the three species Neobacillus dendrensis, Neobacillus soli and Neobacillus cucumis (all 98.6 %). The 16S rRNA gene sequence similarities to the sequences of the type strains of other Neobacillus species were lower than 98.5 %. The average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between the JJ-3T genome assembly and those of the other Neobacillus type strains were <83, <85 and <27 %, respectively. Chemotaxonomic features supported the grouping of the strain to the genus Neobacillus, e.g. the major fatty acids were C15 : 0 anteiso and C15 : 0 iso, the polar lipid profile contained the major components diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine, and the major quinone was menaquinone MK-7. Physiological and biochemical test results were slightly different from those of the most closely related species. For this reason, JJ-3T represents a novel species of the genus Neobacillus, for which we propose the name Neobacillus rhizosphaerae sp. nov., with JJ-3T (= CIP 111895T=LMG 32087T=DSM 111784T=CCM 9084T) as the type strain. We also propose to reclassify Bacillus dielmonensis as Neobacillus dielmonensis comb. nov. based mainly on the results of phylogenomic and conserved signature indel analyses.


Central nervous system active medications and risk for fractures in older women.
Use of central nervous system (CNS) active medications may increase the risk for fractures. Prior studies are limited by incomplete control of confounders. To determine whether use of CNS active medications, including benzodiazepines, antidepressants, anticonvulsants, and narcotics, increases fracture risk in elderly, community-dwelling women, we examined use of these 4 categories of medications in a cohort of 8127 older women and followed the participants prospectively for incident nonspine fractures, including hip fractures. Current use of CNS active medications was assessed by interview with verification of use from containers between 1992 and 1994 and between 1995 and 1996. Use was coded as a time-dependent variable. Incident nonspine fractures occurring after the initial medication assessment until May 31, 1999, were confirmed by radiographic reports. During an average follow-up of 4.8 years, 1256 women (15%) experienced at least one nonspine fracture, including 288 (4%) with first hip fractures. Compared with nonusers, women taking narcotics (multivariate hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.06-1.83) and those taking antidepressants (multivariate HR, 1.25; 95% CI, 0.99-1.58) had increases in the risks for any nonspine fractures. Women taking tricyclic antidepressants and those using selective serotonin reuptake inhibitors (SSRIs) had similar fracture rates. There were no independent associations between benzodiazepine use or anticonvulsant use and risk for nonspine fracture. Women taking antidepressants compared with nonusers had a 1.7-fold increase in the risk for hip fracture (multivariate HR, 1.65; 95% CI, 1.05-2.57). We did not observe independent associations between use of any of the other 3 classes of CNS active medications and risk of hip fracture. Community-dwelling older women taking narcotics have an increased risk for any nonspine fracture, and those taking antidepressants have a greater risk for nonspine fractures, including hip fracture. Rates of fracture were similar in women taking tricyclic antidepressants and those using SSRIs. Benzodiazepine use and anticonvulsant use were not independently associated with an increased risk of nonspine fractures, including hip fracture.


Multipotential mesoangioblast stem cell therapy in the mdx/utrn-/- mouse model for Duchenne muscular dystrophy.
Duchenne muscular dystrophy is a progressive, lethal muscle-wasting disease for which there is no treatment. We have isolated wild-type mesoangioblasts from aorta and tested their effectiveness in alleviating severe muscle disease in the dystrophin/utrophin knockout (mdx/utrn-/-) mouse model for Duchenne muscular dystrophy. Mesoangioblast clones express Sca-1 and Flk-1 and differentiate into smooth and skeletal muscle, glial cells and adipocytes in vitro. Mesoangioblasts proliferate in vivo, incorporate into muscle fibers, form new fibers, and promote synthesis of dystrophin and utrophin. Muscle fibers that have incorporated mesoangioblasts, as well as surrounding fibers, are protected from damage, with approximately 50-fold less damage than fibers in muscle injected with saline. Some mesoangioblasts localize beneath the basal lamina and express c-met, whereas others differentiate into smooth muscle cells at the periphery of vessels and express alpha-smooth muscle actin. In mdx/utrn-/- muscle, some mesoangioblasts also form Schwann cells. Mesoangioblasts differentiate into multiple cell types damaged during the progression of severe muscle disease and protect fibers from damage. As such, they are good candidates for therapy of Duchenne muscular dystrophy and perhaps other neuromuscular diseases.


Lipocalin 2 Deficiency Restrains Aging-Related Reshaping of Gut Microbiota Structure and Metabolism.
Gut microbiota modulate age-associated changes in metabolism, innate immune responses, and cognitive function. However, the involvement of host factors in the regulation of age-dependent gut microbial structure and intestinal inflammation is largely unknown. Lipocalin 2 (Lcn2) has previously been identified as an adipocytokine and characterized as an important regulator of diet-induced obesity and inflammation. Previous studies have shown that Lcn2 plays a role in high fat diet-induced reshaping of gut microbiota and intestinal inflammation. However, the role of Lcn2 in the regulation of aging-related reshaping of gut microbiota is unclear. Herein, we demonstrate that fecal levels of Lcn2 are reduced during aging. Age reshaped gut microbiota composition in wild-type (WT) mice. Interestingly, Lcn2 deficiency diminished this effect of aging in Lcn2 knockout (LKO) mice, leading to decreased bacterial diversity and increased Firmicutes to Bacteroidetes (F to B) ratio. Specifically, we identified 16 bacteria at the family level that were differentially abundant between WT and LKO mice at old age. Several health-promoting bacteria, including SCFA-producing bacteria, were significantly less prevalent in old LKO mice compared to WT mice, indicating that Lcn2 deficiency shifts the aging-related gut microbial community towards an unhealthy population and lowers microbial butyrate production. Our results provide a line of evidence that Lcn2 plays a role in the control of aging-related reshaping of gut microbiota composition and metabolites.


Pancuronium pharmacokinetics in patients with liver cirrhosis.
The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.


Cytopathological and Microbiological Profile of Tuberculous Lymphadenitis in HIV-Infected Patients with Special Emphasis on Its Corroboration with CD4+ T-Cell Counts.
The present study was performed to evaluate various cytological patterns and acid fast bacillus (AFB) grades in HIV-infected patients with tuberculous lymphadenitis and to correlate these with each other as well as with peripheral CD4+ T-cell counts. Ninety-two HIV-seropositive patients, cytologically diagnosed with tuberculous lymphadenitis, were evaluated. Fine needle aspiration cytology was performed as an outpatient procedure. Sonographic guidance was sought for internally sited lymph nodes. Cytopathological details were assessed on routinely stained and Ziehl-Neelsen-stained smears. Appropriate AFB grades were assigned. CD4+ T-cell counts were obtained immediately. Finally, the cytopathological findings, AFB grades and CD4+ T-cell counts were corroborated with each other. Epithelioid cell granuloma in the presence of caseation appeared to be the most frequent (66.3%) cytomorphology on aspirated smears. AFB grades 3+ (37%) and 4+ (35.9%) were the commonest patterns of bacillary involvement. The mycobacterial density and cytological features significantly correlated with CD4+ T-cell counts. In HIV-associated tuberculous lymphadenitis, AFB grade and CD4+ T-cell counts worsen with the appearance of necrosis. Here, the peripheral CD4+ T-cell counts inversely correlated with bacillary load. Collectively, peripheral CD4+ T-cell counts, cytological findings and AFB grade exemplify the immune status in these patients.


Fracture loads of all-ceramic crowns under wet and dry fatigue conditions.
The aim of this study was to test the hypothesis that fracture loads of fatigued dental ceramic crowns are affected by testing environment and luting cement. One hundred and eighty crowns were prepared from bovine teeth using a lathe. Ceramic crowns were prepared from three types of ceramic systems: an alumina-infiltrated ceramic, a lithia-disilicate-based glass ceramic, and a leucite-reinforced ceramic. For each ceramic system, 30 crowns were cemented with a composite resin cement, and the remaining 30 with a resin-modified glass ionomer cement. For each ceramic system and cement, ten specimens were loaded to fracture without fatiguing. A second group (n = 10) was subjected to cyclic fatigue and fracture tested in a dry environment, and a third group (n = 10) was fatigued and fractured in distilled water. The results were statistically analyzed using one-way ANOVA and Tukey HSD test. The fracture loads of ceramic crowns decreased significantly after cyclic fatigue loading (p<or= 0.05); furthermore, fracture loads of crowns fatigued in a wet environment were statistically lower than those in a dry environment (p < 0.05). Crowns luted with a composite resin cement showed statistically greater fracture loads than those luted with a resin-modified glass ionomer cement (p<or= 0.05). Fracture load of the three ceramic systems was found to be influenced by ceramic composition. Moreover, cement and fatigue condition influenced the fracture loads of the crown specimens evaluated in this study.


Tritium Labeling of Neuromedin S by Conjugation with [3H]N-Succinimidyl Propionate.
The human neuropeptide neuromedin S (NMS) consists of 33 amino acids. The introduction of tritium atoms into NMS has not been described so far. This represents a gap for using [3H]NMS in radioreceptor binding assays or in tracking and monitoring their metabolic pathway. Two approaches for the incorporation of tritium into NMS were explored in this study: (1) halogenation at the His-18 residue followed by catalyzed iodine-127/tritium exchange and (2) conjugation of tritiated N-succinimidyl-[2,3-3H3]propionate ([3H]NSP) to at least one of the three available primary amines of amino acids Ile-1, Lys-15, and Lys-16 in the peptide sequence. Although iodination of histidine was achieved, subsequent iodine-127/deuterium exchange was unsuccessful. Derivatization at the three possible amino positions in the peptide using nonradioactive NSP resulted in a mixture of unconjugated NSM and 1- to 3-conjugations at different amino acids in the peptide sequence. Each labeling position in the mixture was assigned following detailed LC-MS/MS analysis. After separating the mixture, it was shown in an in vitro fluorometric imaging plate reader (FLIPR) and in a competitive binding assay that the propionyl-modified NMS derivatives were comparable to the unlabeled NMS, regardless of the degree of labeling and the labeling position(s). A molecular simulation with NMS in the binding pocket of the protein neuromedin U receptor 2 (NMUR2) confirmed that the possible labeling positions are located outside the binding region of NMUR2. Tritium labeling was achieved at the N-terminal Ile-1 using [3H]NSP in 7% yield with a radiochemical purity of >95% and a molar activity of 90 Ci/mmol. This approach provides access to tritiated NMS and enables new investigations to characterize NMS or corresponding NMS ligands.


Salient space detection algorithm for signal extraction from contaminated and distorted spectrum.
An algorithm for signal extraction from a contaminated and distorted spectrum is proposed. First, this algorithm combines the salient space of the spectrum and the statistical characteristics of the noise to detect signal regions at different scales. Second, it extracts signals by subtracting the baseline from the spectrum in the signal regions. The baseline is fitted by segmented polynomial functions. This algorithm has been applied to simulated and experimental data, and the results show that this algorithm can accurately and automatically extract signals with varying widths from a contaminated spectrum. This method minimizes the influence of baseline distortion and exhibits good anti-noise capability and high real-time performance.


Apneic Oxygenation During Prolonged Laryngoscopy in Obese Patients: a Randomized, Double-Blinded, Controlled Trial of Nasal Cannula Oxygen Administration.
Obese patients have a propensity to desaturate during induction of general anesthesia secondary to their reduced functional residual capacity and increased oxygen consumption. Apneic oxygenation can provide supplemental oxygen to the alveoli, even in the absence of ventilation, during attempts to secure the airway. In this study, we hypothesized that oxygen administration through a nasopharyngeal airway and standard nasal cannula during a simulated prolonged laryngoscopy would significantly prolong the safe apneic duration in obese patients. One hundred thirty-five obese patients undergoing non-emergent surgery requiring general anesthesia were randomized to either the control group or to receive apneic oxygenation with air versus oxygen. All patients underwent a standard intravenous induction. For patients randomized to receive apneic oxygenation, a nasopharyngeal airway and standard nasal cannula were inserted. A simulated prolonged laryngoscopy was performed to determine the duration of the safe apneic period, defined as the beginning of laryngoscopy until the peripheral oxygen saturation (SpO2) reached 95%. The oxygen group had a median safe apneic duration that was 103 s longer than the control group. The lowest mean SpO2 value during the induction period was 3.8% higher in the oxygen group compared to the control group. Following intubation, patients in the oxygen group had a mean end tidal carbon dioxide (ETCO2) level that was 3.0 mmHg higher than patients in the control group. In obese patients, oxygen insufflation at 15 L/min through a nasopharyngeal airway and standard nasal cannula can significantly increase the safe apneic duration during induction of anesthesia.


Quality of life and psychosocial situation before and after a lung, liver or an allogeneic bone marrow transplant. Results from a prospective study.
Only few comparative prospective studies have been published on psychosocial issues of organ transplant. This study investigated patient groups with various organ transplants with respect to their quality of life and psychosocial situation before and after surgery. 76 patients receiving an organ transplant (lung n = 22, liver n = 26, allogeneic bone marrow n = 28) were investigated with regard to quality of life (SF-36), life satisfaction (FLZ), social support (F-SozU), and psychological symptoms (HADS-D) before (T0) as well as six (T1) and twelve (T2) months after transplant. In the pre-transplant period the values of the psychosocial variables were partly lower than those of the community normal sample. After transplant lung and bone marrow patients reported less anxiety and depression and a higher life satisfaction, and liver patients reported less depression, compared to the norms. Quality of life, life satisfaction and psychological symptoms of all patients improved significantly post-transplant, whereas the perceived social support decreased. Contrary to the other groups, the psychological well-being of liver transplant recipients was deteriorating between T1 and T2. An organ transplant improved the patients' quality of life and psychosocial situation to a great extent. This effect was better in lung and bone marrow than in liver transplant patients.


Changes in gene expression in PBMCs profiles of PPARα target genes in obese and non-obese individuals during fasting.
The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Q-PCR was utilized to assess the mRNA expression levels of target genes. In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors.


Modulation by thyroid hormones of the development of external plexiform layer in the rat olfactory bulb.
Width of the external plexiform layer in olfactory bulbs and mean area of mitral and granule cell dendritic and glial processes were measured of normal, hypo- and hyperthyroid rat pups at the age of 24 days. Hypothyroidism was induced by treating the rats with a reversible goitrogen 6-n-propyl-2-thiouracil dissolved in their drinking water, while the hyperthyroid group was given water containing thyroxine. The 6-n-propyl-2-thiouracil treatment was begun on gestational day 18 and on the day of birth. Thyroxine treatment started on the day of birth. Both treatments were continued till the day of sacrifice. A significant decrease in the width of the external plexiform layer of the olfactory bulb in the prenatally 6-n-propyl-2-thiouracil treated group and a significant increase in the width of the external plexiform layer of the hyperthyroid group was shown by the Student's paired t-test. The areas of neuronal and glial processes were measured at electron microscopic level by using an IBAS image analysing system. A significant decrease was found by the Kruskal-Wallis test and Dunn's range test in the mean area of (1) mitral cell dendrites in the prenatal 6-n-propyl-2-thiouracil treated group, (2) granule cell dendrites in both the postnatally 6-n-propyl-2-thiouracil treated and in the hyperthyroid groups and (3) glial processes in the thyroxine treated group comparing to controls.


Self-Assembled Hierarchical Superstructures from the Benzene-1,3,5-Tricarboxamide Supramolecules for the Fabrication of Remote-Controllable Actuating and Rewritable Films.
The well-defined hierarchical superstructures constructed by the self-assembly of programmed supramolecules can be organized for the fabrication of remote-controllable actuating and rewritable films. To realize this concept, we newly designed and synthesized a benzene-1,3,5-tricarboxamide (BTA) derivative (abbreviated as BTA-3AZO) containing photoresponsive azobenzene (AZO) mesogens on the periphery of the BTA core. BTA-3AZO was first self-assembled to nanocolumns mainly driven by the intermolecular hydrogen-bonds between BTA cores, and these self-assembled nanocolumns were further self-organized laterally to form the low-ordered hexagonal columnar liquid crystal (LC) phase below the isotropization temperature. Upon cooling, a lamello-columnar crystal phase emerged at room temperature via a highly ordered lamello-columnar LC phase. The three-dimensional (3D) organogel networks consisted of fibrous and lamellar superstructures were fabricated in the BTA-3AZO cyclohexane-methanol solutions. By tuning the wavelength of light, the shape and color of the 3D networked thin films were remote-controlled by the conformational changes of azobenzene moieties in the BTA-3AZO. The demonstrations of remote-controllable 3D actuating and rewritable films with the self-assembled hierarchical BTA-3AZO thin films can be stepping stones for the advanced flexible optoelectronic devices.