[Effect of metabolism activation on the oxidative cell damage induced by cigarette smoking].
To explore the effect of metabolic activation on the oxidative cell damage induced by mainstream smoke (MS). A549 cells were treated with different concentrations of MS for 2 hours in the presence and absence of S9 mix. ROS levels were determined. DNA and chromosome damages were detected. The activities of SOD and GSH-Px were measured. With different concentrations of MS treatment, the contents of ROS in the cells with S9 mix were significantly higher than those without S9 mix (P<0.05). More serious chromosome and DNA damages in the cells with S9 mix were observed than those without S9 mix. The micronucleus rate, comet rate, L Tail and OTM in the cells with S9 mix were significantly higher than those without S9 mix (P<0.05). With increased dose of MS, the activities of SOD and GSH-Px decreased in both cells with and without S9 mix. But the tendency of decrease in the cells with S9 mix was more obvious than those without S9 mix (P<0.05). MS induces oxidative damage in A549 cells and the metabolic activations could increase the oxidative stress and potentiate the cellular genotoxicity.


Lack of head sparing following third-trimester caloric restriction among Tanzanian Maasai.
The reduction of food intake during pregnancy is part of many cultural and religious traditions around the world. The impact of such practices on fetal growth and development are poorly understood. Here, we examined the patterns of diet intake among Maasai pregnant women and assessed their effect on newborn morphometrics. We recruited 141 mother-infant pairs from Ngorongoro Conservation Area (NCA) in Northern Tanzania and quantified dietary intake and changes in maternal diet during pregnancy. We obtained measurements of body weight (BW) and head circumference (HC) at birth. We found that Maasai women significantly reduced their dietary intake during the third trimester, going from an average of 1601 kcal/day during the first two trimesters to 799 kcal/day in the final trimester. The greatest proportion of nutrient reduction was in carbohydrates. Overall, 40% of HC Z-scores of the NCA sample were more than 2 standard deviations below the WHO standard. Nearly a third of neonates classify as low birth weight (< 2500g). HC was smaller relative to BW in this cohort than predicted using the WHO standard. This contrasts markedly to a Tanzanian birth cohort obtained at the same time in an urban context in which only 12% of infants exhibited low weight, only two individuals had HC Z-scores < 2 and HC's relative to birth weight were larger than predicted using the WHO standards. The surprising lack of head sparing in the NCA cohort suggests that the impact of third trimester malnutrition bears further investigation in both animal models and human populations, especially as low HC is negatively associated with long term health outcomes.


[Principles and perspectives of primary biliary cirrhosis therapy].
A survey of existing methods of pathogenetic and symptomatic treatment of primary biliary cirrhosis has been made and it has reviewed prospective directions of its therapy. Is also presents a retrospective analysis of our own data of S-adenosylmethionine (Heptral) in 27 patients PBC receiving UDCA basic therapy. In its application intravenously of 400 mg 2 times daily for 3 weeks showed a reduction in the severity of pruritus, assessed by visual analogue scale, a subjective decrease fatigability and a decrease level of serum bilirubin.


[On clinical manifestations of rotavirus-related gastroenteritis and possible links with its viral phoretype].
The results are presented of the study of rotavirus gastroenteritis course in 45 patients (23 children and 22 adults) with different phoretypes. Phoretypical heterogeneity of rotavirus population was discovered among which the "long" phoretype prevailed. Rotavirus infection ran with diverse clinical symptoms: mild, moderate and severe. A lethal outcome occurred in an old male patient. No correlation was found between the phoretype and severity of the disease.


Patient Experiences Using a Self-Monitoring App in Eating Disorder Treatment: Qualitative Study.
The Recovery Record smartphone app is a self-monitoring tool for individuals recovering from an eating disorder. Unlike traditional pen-and-paper meal diaries, which are often used in eating disorder treatment, the app holds novel features, such as meal reminders, affirmations, and patient-clinician in-app linkage, the latter allowing for clinicians to continuously monitor patients' app data. To explore patients' experiences with using Recovery Record as part of outpatient eating disorder treatment. A total of 41 patients from a Danish eating disorder treatment facility were included in the study. All 41 patients participated in participant observations of individual or group treatment sessions, and 26 were interviewed about their experiences with using the app in treatment. The data material was generated and analyzed concurrently, applying the inductive methodology of Interpretive Description. The patients' experiences with Recovery Record depended on its app features, the impact of these features on patients, and their specific app usage. This patient-app interaction affected and was affected by changeable contexts making patients' experiences dynamic. The patient-app interaction affected patients' placement of specific Recovery Record app features along a continuum from supportive to obstructive of individual everyday life activities including the eating disorder treatment. As an example, some patients found it supportive being notified by their clinician when their logs had been monitored as it gave them a sense of relatedness. Contrarily, other patients felt under surveillance, which was obstructive, as it made them feel uneasy or even dismissing the app. Some patients experienced the app and its features as mostly supportive of their everyday life and the eating disorder treatment, while others experienced it primarily as obstructive. When applying apps in eating disorder treatment, we therefore recommend that patients and clinicians collaborate to determine how the app in question best fits the capacities, preferences, and treatment needs of the individual patient. Thus, we encourage patients and clinicians to discuss how specific features of the applied app affect the individual patient to increase the use of supportive features, while limiting the use of obstructive ones.


[Energy exchange in mitochondria and contractility of bundles of glycerinated myocardial fibers in traumatic shock].
The state of energy exchange on the basis of respiratory chain reactions of myocardial mitochondria and contractility of bundles of glycerinated muscle fibers in traumatic shock, were investigated. The mitochondria isolated from animal myocardium at the terminal stage of traumatic shock were found to be capable to carry out oxidative phosphorylation at the level typical for healthy animal mitochondria. Parallel tensometric analyses of contractility of bundles of glycerinated muscle fibers showed that in rats and dogs with traumatic shock the most pronounced changes occur in isometric tension and specific power. At the same time relative fiber shortening under isotonic conditions is insignificantly reduced.


[The male factor. I. Testicular function and gametogenesis].
The knowledge and treatment of human reproduction impairments have had an outstanding development during the last 15 years, mainly in topics related with infertility and sterility. Unfortunately in the area of male reproduction development has not been the same and despite the efforts accomplished, progress in the diagnosis and therapeutics of male infertility is limited. The functions of the male gonad are sperm production as well as the synthesis and secretion of steroid hormones, mainly testosterone. The efficient regulation of these functions depends on both the precise pituitary secretion of gonadotropic hormones and the endocrine, paracrine and autocrine responses of the testicular somatic cells to this stimulation. In this review we discuss the main events associated with the spermatogenic process, including the interactions among the testicular somatic cells and some characteristics of the physiological function of the hypothalamus-pituitary-testicle axis, as well as some pathophysiological states related to male infertility due to "pretesticular causes".


Nanoscale variation of bioadhesive substrates as a tool for engineering of cell matrix assembly.
Although molecular and physical mechanisms of fibroblast matrix assembly have been widely investigated, the role of adhesive ligand presentation on matrix assembly has only been recently probed (Pereira et al. Tissue Eng., 2007). In the present study, various-sized albumin-derived nanocarriers (ANCs) were fabricated as nanoscale organization units for functionalization with the cell adhesion domain of fibronectin. The adhesion, morphology, and matrix assembly of human dermal fibroblasts were compared on substrate-deposited, ligand-ANCs of varying size. At early time points, fibroblast attachment, stress fiber formation, and spreading were higher on functionalized, larger-sized carriers than on smaller carriers. Matrix assembly was greatest at the highest ligand density on larger nanocarriers but was undetectable at the same ligand density on smaller carriers. Tracking of fluorophore-encapsulated ANCs showed that larger carriers were displaced less than smaller carriers and that atomic force microscopy of ligand-ANCs binding to adherent cells demonstrated that the larger ligand-ANCs required larger dissociation forces. Taken together, these data suggest that the greater inertia of larger adhesive nanocarriers may generate more cellular tension, which in turn, promotes up-regulation of matrix assembly. Thus, the size of the nanocarrier and the density of ligand on that nanocarrier combine to dictate the early kinetics of fibroblast matrix assembly. These insights may be useful for understanding cell-matrix interactions, as well as for development of bioactive materials with defined cell-adhesive activities such as wound repair and matrix remodeling events.


First detection of herpesvirus and hemosporidians in the endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus).
Pathogens affect wild bird populations worldwide, contributing to their decline. Considering the scarce health data regarding the endangered Pyrenean Capercaillie (Tetrao urogallus aquitanicus), we molecularly surveyed selected pathogens (Newcastle disease virus, Avian influenza virus, Chlamydia psittaci, avian pathogenic Escherichia coli, Campylobacter jejuni, and Salmonella spp.) in 30 Pyrenean Capercaillie feces collected in the field (Catalonia, northeastern Spain). Additionally, swab and tissue samples from eight wild Pyrenean Capercaillies of Catalonia and Andorra were molecularly tested for herpesvirus and hemosporidians (Plasmodium spp., Haemoproteus spp., and Leucocytozoon spp.). All fecal samples were negative for the pathogens tested. Nevertheless, we detected a novel herpesvirus in 50% (4/8) of the Pyrenean Capercaillies, and hemosporidian DNA in 62.5% (5/8) of the tissue samples (i.e., Haemoproteus sp. [4 of 8] and/or Leucocytozoon sp. [3 of 8]). To our knowledge, this is the first detection of herpesvirus and hemosporidians infections in Pyrenean Capercaillies. The putative novel herpesvirus belongs to the genus Iltovirus. The presence of hemosporidian parasites in this mountain bird species is of concern, and could be related to the marked increase in the average temperature in the Pyrenees as a consequence of climate change. Our findings are fundamental to improve the conservation plans for the endangered Pyrenean Capercaillie population.


The role of angiogenic growth factors in organogenesis.
Angiogenic growth factors are a class of molecules which exert a fundamental role in the process of blood vessel formation. Besides vasculogenic and angiogenic properties, these compounds mediate a complex series of patterning activities during organogenesis. Angiogenic factors cooperate in the growth and development of embryo tissues in a cross-talk between endothelial cells and tissue cells. It is well established that many tissue-derived factors are involved in blood vessel formation, but there is now emerging evidence that angiogenic factors and endothelial cells themselves represent a crucial source of instructive signals to non-vascular tissue cells during organ development. Thus, angiogenic factors and endothelial cell signalling are currently believed to provide fundamental cues for cell fate specification, embryo patterning, organ differentiation and postnatal tissue remodelling. This review article will summarize some of the recent advances in our understanding of the role of angiogenic factors and endothelial cells as effectors in organ formation.


Identification of REO1, a gene involved in negative regulation of COX5b and ANB1 in aerobically grown Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the COX5a and COX5b genes constitute a small gene family that encodes two forms of cytochrome c oxidase subunit V, Va and Vb, either of which can provide a function essential for cytochrome c oxidase activity and respiration. In aerobically grown wild-type yeast cells, Va is the predominant form of subunit V. The COX5b gene alone does not produce enough Vb to support a respiration rate sufficient to allow growth on nonfermentable carbon sources. By selecting for mutations that increase the respiratory capacity of a strain deleted for COX5a, we have identified a gene that is involved in negative regulation of COX5b expression under aerobic growth conditions. Each of four independently isolated reo1 mutations are shown to be recessive, unlinked to COX5b, but dependent on COX5b for phenotypic expression. The mutations define a single complementation and linkage group: designated as REO1 for regulator of expression of oxidase. reo1 mutations increase expression of COX5b in aerobically grown cells, but not in anaerobically grown cells, where expression is already elevated. These mutations have no effect on COX5a, the other member of this small gene family which is positively regulated by heme and oxygen. The REO1 gene does play a role in repression of ANB1, a gene that is normally repressed under aerobic but not anaerobic conditions. Neither rox1 or rox3 mutations, which have previously been shown to increase ANB1 expression, are in the same complementation group as reo1 mutations.


Short- and Long-Range Mechanical and Chemical Interphases Caused by Interaction of Boehmite (γ-AlOOH) with Anhydride-Cured Epoxy Resins.
Understanding the interaction between boehmite and epoxy and the formation of their interphases with different mechanical and chemical structures is crucial to predict and optimize the properties of epoxy-boehmite nanocomposites. Probing the interfacial properties with atomic force microscopy (AFM)-based methods, especially particle-matrix long-range interactions, is challenging. This is due to size limitations of various analytical methods in resolving nanoparticles and their interphases, the overlap of interphases, and the effect of buried particles that prevent the accurate interphase property measurement. Here, we develop a layered model system in which the epoxy is cured in contact with a thin layer of hydrothermally synthesized boehmite. Different microscopy methods are employed to evaluate the interfacial properties. With intermodulation atomic force microscopy (ImAFM) and amplitude dependence force spectroscopy (ADFS), which contain information about stiffness, electrostatic, and van der Waals forces, a soft interphase was detected between the epoxy and boehmite. Surface potential maps obtained by scanning Kelvin probe microscopy (SKPM) revealed another interphase about one order of magnitude larger than the mechanical interphase. The AFM-infrared spectroscopy (AFM-IR) technique reveals that the soft interphase consists of unreacted curing agent. The long-range electrical interphase is attributed to the chemical alteration of the bulk epoxy and the formation of new absorption bands.


Association testing to detect gene-gene interactions on sex chromosomes in trio data.
Autism Spectrum Disorder (ASD) occurs more often among males than females in a 4:1 ratio. Among theories used to explain the causes of ASD, the X chromosome and the Y chromosome theories attribute ASD to the X-linked mutation and the male-limited gene expressions on the Y chromosome, respectively. Despite the rationale of the theory, studies have failed to attribute the sex-biased ratio to the significant linkage or association on the regions of interest on X chromosome. We further study the gender biased ratio by examining the possible interaction effects between two genes in the sex chromosomes. We propose a logistic regression model with mixed effects to detect gene-gene interactions on sex chromosomes. We investigated the power and type I error rates of the approach for a range of minor allele frequencies and varying linkage disequilibrium between markers and QTLs. We also evaluated the robustness of the model to population stratification. We applied the model to a trio-family data set with an ASD affected male child to study gene-gene interactions on sex chromosomes.


Minimally invasive spine surgery for adult degenerative lumbar scoliosis.
Historically, adult degenerative lumbar scoliosis (DLS) has been treated with multilevel decompression and instrumented fusion to reduce neural compression and stabilize the spinal column. However, due to the profound morbidity associated with complex multilevel surgery, particularly in elderly patients and those with multiple medical comorbidities, minimally invasive surgical approaches have been proposed. The goal of this meta-analysis was to review the differences in patient selection for minimally invasive surgical versus open surgical procedures for adult DLS, and to compare the postoperative outcomes following minimally invasive surgery (MIS) and open surgery. In this meta-analysis the authors analyzed the complication rates and the clinical outcomes for patients with adult DLS undergoing complex decompressive procedures with fusion versus minimally invasive surgical approaches. Minimally invasive surgical approaches included decompressive laminectomy, microscopic decompression, lateral and extreme lateral interbody fusion (XLIF), and percutaneous pedicle screw placement for fusion. Mean patient age, complication rates, reoperation rates, Cobb angle, and measures of sagittal balance were investigated and compared between groups. Twelve studies were identified for comparison in the MIS group, with 8 studies describing the lateral interbody fusion or XLIF and 4 studies describing decompression without fusion. In the decompression MIS group, the mean preoperative Cobb angle was 16.7° and mean postoperative Cobb angle was 18°. In the XLIF group, mean pre- and postoperative Cobb angles were 22.3° and 9.2°, respectively. The difference in postoperative Cobb angle was statistically significant between groups on 1-way ANOVA (p = 0.014). Mean preoperative Cobb angle, mean patient age, and complication rate did not differ between the XLIF and decompression groups. Thirty-five studies were identified for inclusion in the open surgery group, with 18 studies describing patients with open fusion without osteotomy and 17 papers detailing outcomes after open fusion with osteotomy. Mean preoperative curve in the open fusion without osteotomy and with osteotomy groups was 41.3° and 32°, respectively. Mean reoperation rate was significantly higher in the osteotomy group (p = 0.008). On 1-way ANOVA comparing all groups, there was a statistically significant difference in mean age (p = 0.004) and mean preoperative curve (p = 0.002). There was no statistically significant difference in complication rates between groups (p = 0.28). The results of this study suggest that surgeons are offering patients open surgery or MIS depending on their age and the severity of their deformity. Greater sagittal and coronal correction was noted in the XLIF versus decompression only MIS groups. Larger Cobb angles, greater sagittal imbalance, and higher reoperation rates were found in studies reporting the use of open fusion with osteotomy. Although complication rates did not significantly differ between groups, these data are difficult to interpret given the heterogeneity in reporting complications between studies.


Prevalence and Associated Factors of Thyroid Incidentaloma among Adult People Attending Gondar University Hospital, Northwest Ethiopia.
Incidentally discovered thyroid lesions have become highly common in the development and more frequent utilization of highly sensitive imaging modalities, like ultrasound. However, little is known about its prevalence and associated factors in Ethiopia. The aim of this study was to determine the prevalence of thyroid incidentalomas and associated factors through ultrasound (US) among adults attending Gondar University Hospital. A hospital-based cross-sectional study was carried out on 290 adults aged 15 years and above. Out of the adults who visited the hospital during the study, those who neither had history of thyroid disease, thyroid surgery, nor clinically palpable thyroid nodules were involved in the investigation. The participants were examined using a high frequency linear-array transducer (7 MHz). For comparing men and women, the unpaired t-test was used. Binary logistic analysis was used to identify the associated factors, and a P-value < 0.05 was considered statistically significant. The frequency of thyroid incidentaloma was found to be 33.4% (95% CI: 27.9, 38.9). Thyroid incidentaloma was detected in 42.4% of the females and 22.7% of the males (P<0.001). About 63% had single and 37% multiple thyroid nodules. About 25.8% had thyroid nodules greater than 1cm. In the multivariable logistic regression analysis, increasing age (AOR=5.96; 2.34, 15.15) and female sex (AOR=3.01; 1.73, 5.26) were significantly associated with thyroid incidentalomas. The frequency of thyroid incidentaloma (TI) was found to be high in this study and much higher among older women. Solitary and small sized thyroid nodules were commonly seen in the study.


Left ventricular pump function in renal hypertensive dogs with cardiac hypertrophy.
We compared open-chest left ventricular (LV) pump performance after autonomic blockade under controlled loading conditions in normal dogs and in dogs where chronic renovascular hypertension had produced moderate concentric LV hypertrophy (LVH). Mean LV pressure (MLVP) provided a measure of ventricular load independent of vascular properties. We found an inverse relationship between MLVP and cardiac index (CI) in both groups when peripheral resistance was altered at constant left atrial pressure. However, CI declined significantly less in LVH hearts as MLVP was increased. The slope of the linear MLVP-CI plot (LV source resistance) was 1.91 times the value observed in normal dogs. LVH hearts developed more steady-flow external power than their normal counterparts, and the power optimum was reached at a much higher mean arterial pressure. Isovolumic maximum rate of LVP rise was 1.28 times higher in LVH than normal dogs (P less than 0.01) in proportion to the increase in wall thickness. Our results suggest that additional muscle with normal contractile properties and greater emptying due to the increased wall-to-lumen ratio accounted for the increased pump performance in LVH.


[Surgical treatment of hip fractures in 90-year-olds].
During 1973-1987 178 patients of 90 years and over were operated for a fracture of the hip in the Diaconesseninrichting 'Bronovo', The Hague. Fifty patients were suffering of senile dementia which made reactivation difficult and contributed to 43% of the mortality. The overall in-hospital mortality was 18% and the survivors were discharged after 35 days on average. Patients with lateral and pertrochanteric fractures were treated according to McLaughlin (6), to Ender (74) and with a dynamic hip screw (17) and medial fractures with a dynamic hip screw (54) or a prosthesis (27). The in-hospital mortality rates were 16, 28, 6, 11 en 11% respectively. Postoperatively 7 Ender pins sagged out and 6 patients treated with a dynamic hip screw secondarily needed a prosthesis, 3 of them after discharge. It is advised to use Ender pins in lateral or pertrochanteric fractures in inactive patients only, and a dynamic hip screw in active patients; in medial fractures a dynamic hip screw only in inactive patients and in others a prosthesis. An increase in the number of very old people with hip fractures is to be expected in the near future.


Fluid transport and tubular intercellular spaces in reptilian kidneys.
Renal tubules of crocodiles, lizards, snakes, and turtles have intercellular spaces similar in type to those observed in the mammalian gall bladder, but different from those of mammalian renal tubules. The fluid movements across renal tubules of reptiles are correlated with the width of the tubular intercellular spaces. In the proximal tubules, where transport is always isosmotic, the spaces are open whenever the tubular epithelium is tranporting, but closed when no transport is taking place. In distal tubules, intercellular spaces are wide open when the osmolality of the urine is close to that of the blood, that is, when the fluid resorbed is almost isosmotic to the tubular fluid. The apical two-thirds of the intercellular spaces are closed when the urine is hypoosmotic. They are also closed when the tubules are not transporting, as in collapsed tubules or tubules poisoned with ouabain. Thus, as in the gall bladder, the open intercellular spaces appear to be found whenever there is fluid transport across the epithelium.


Treatment of parkinsonism with N-n-propyl norapomorphine and levodopa (with or without carbidopa).
The effects of the concomitant administration of N-n-propyl norapomorphine (NPA) and levodopa, with and without carbidopa, were studied in 12 patients with unsatisfactory symptom control. Double-blind evaluation of the effects of NPA with suboptimal doses of levodopa or levodopa plus carbidopa (Sinemet) showed a mean overall improvement of 44% (20% to 74%) in nine patients and improvement of the "on-off" effect in five. Dyskinesia diminished in some patients after diminution of basal medication. In three patients, plasma dopa and growth hormone patterns did not differ substantially with and without NPA. The magnitude and timing of the therapeutic and side effects did not correlate with the pattern of growth hormone secretion, which suggests that this hormone might not be instrumental in the induction of these effects. N-n-propyl norapomorphine is a useful adjunct in the long-term management of patients with unsatisfactory response to levodopa.


Impact of dementia on hospitalization.
The purpose of this study was to analyze and determine the prevalence and clinical characteristics of hospitalized dementia patients compared with nondemented patients. We examined hospital discharge database records dated 1998-2003 from public hospitals in Andalusia, Spain. We used ICD-9-CM codes to identify patients with dementia. The variables examined included age, length of stay, discharge diagnosis, diagnostic-related groups, and mortality of both dementia and nondementia patients over 65 years of age. A diagnosis of dementia was documented for 40,482 cases. The prevalence of dementia increased from 3.43% to 4.64% between 1998 and 2003 and was higher among older patients and women. Dementia was the reason for admission in 5.6% of cases. Medical reasons constituted 82.4% of admittances. Dementia patients had hip surgery more frequently than patients without dementia, and other procedures (orthopedic surgery, cataracts, or hernia repair) were less frequent (p < 0.001). The mean duration of the hospital stay was longer (13.4 vs. 10.7 days) and the intra-hospital mortality rate was greater (19.3% vs. 8.7%) for patients with dementia compared to those without dementia. Dementia was an independent predictor of mortality (OR 1.77; 95% CI 1.72-1.82). Dementia is increasing among hospitalized patients. Dementia patients have different reasons for hospitalization and higher mortality. It is necessary to identify these differences and to improve the hospital care of dementia patients.


Malignant glioma in laboratory workers.
In 1989 an increased risk of cancer, with a higher than expected incidence of brain tumours, was reported in laboratory workers at the Pasteur Institute, Paris. Three cases of primary brain tumours occurring in three laboratory workers from one laboratory in a district general hospital also came to light. Although this may have been due to coincidence or geographic clustering, the need for stringent safety standards in all laboratories is reiterated, and it is proposed that a national register should be established to record the causes of death in laboratory workers.


A phantom extinction? New insights into extinction dynamics of the Don-hare Lepus tanaiticus.
The Pleistocene to Holocene transition was accompanied by a worldwide extinction event affecting numerous mammalian species. Several species such as the woolly mammoth and the giant deer survived this extinction wave, only to go extinct a few thousand years later during the Holocene. Another example for such a Holocene extinction is the Don-hare, Lepus tanaiticus, which inhabited the Russian plains during the late glacial. After being slowly replaced by the extant mountain hare (Lepus timidus), it eventually went extinct during the middle Holocene. Here, we report the phylogenetic relationship of L. tanaiticus and L. timidus based on a 339-basepair (bp) fragment of the mitochondrial D-loop. Phylogenetic tree- and network reconstructions do not support L. tanaiticus and L. timidus being different species. Rather, we suggest that the two taxa represent different morphotypes of a single species and the extinction of 'L. tanaiticus' represents the disappearance of a local morphotype rather than the extinction of a species.


Smoking cessation practices in the dental setting.
According to the US Centers for Disease Control, approximately 20.6% of the American adult population currently smokes cigarettes. There is no doubt that tobacco use has a negative effect on oral and general health. Dentists can be effective in assessing their patients' smoking status, health beliefs, and related behavior patterns. A total of 608 patients-smokers, former smokers, and nonsmokers-participated in this study. The Five A's protocol was utilized with follow-up interviews to assess smoking cessation (quit rates) among the patients. Of the 608 subjects, 170 (28%) were current smokers, 140 (23%) were former smokers, and 298 (49%) had never smoked. Females comprised 56% of the study group. Of the 170 smokers who were assessed at baseline, successful follow-ups were performed with 64 (38%). Based on a follow-up of these smokers, the 7-day abstinence quit rate was 22%. Among participants who received nicotine replacement therapy (NRT), 40% quit. Of the participants who did not receive NRT, 19% quit.


Six years of wild bee monitoring shows changes in biodiversity within and across years and declines in abundance.
Wild bees form diverse communities that pollinate plants in both native and agricultural ecosystems making them both ecologically and economically important. The growing evidence of bee declines has sparked increased interest in monitoring bee community and population dynamics using standardized methods. Here, we studied the dynamics of bee biodiversity within and across years by monitoring wild bees adjacent to four apple orchard locations in Southern Pennsylvania, USA. We collected bees using passive Blue Vane traps continuously from April to October for 6 years (2014-2019) amassing over 26,000 bees representing 144 species. We quantified total abundance, richness, diversity, composition, and phylogenetic structure. There were large seasonal changes in all measures of biodiversity with month explaining an average of 72% of the variation in our models. Changes over time were less dramatic with years explaining an average of 44% of the variation in biodiversity metrics. We found declines in all measures of biodiversity especially in the last 3 years, though additional years of sampling are needed to say if changes over time are part of a larger trend. Analyses of population dynamics over time for the 40 most abundant species indicate that about one third of species showed at least some evidence for declines in abundance. Bee family explained variation in species-level seasonal patterns but we found no consistent family-level patterns in declines, though bumble bees and sweat bees were groups that declined the most. Overall, our results show that season-wide standardized sampling across multiple years can reveal nuanced patterns in bee biodiversity, phenological patterns of bees, and population trends over time of many co-occurring species. These datasets could be used to quantify the relative effects that different aspects of environmental change have on bee communities and to help identify species of conservation concern.


The Effect of the Length and Distribution of Implants for Fixed Prosthetic Reconstructions in the Atrophic Posterior Maxilla: A Finite Element Analysis.
In this study, different prosthetic designs that could be applied instead of advanced surgical techniques in atrophic maxilla were evaluated with finite element analysis. Atrophic posterior maxilla was modeled using computer tomography images and four models were prepared as follows: Model 1 (M1), two implants supporting a three-unit distal cantilever prosthesis; Model 2 (M2), two implants supporting a three-unit conventional fixed partial denture; Model 3 (M3), three implants supporting three connected crowns; and Model 4 (M4), two implants supporting two connected crowns. Implants 4 mm in width and 8 mm or 13 mm in length were used. A linear three-dimensional finite element programme was used for analysis. The maximum principle stress (tensile) and minimum principle stress (compressive) were used to display stress in cortical and cancellous bones. The von Mises criteria were used to evaluate the stress on the implants. M1 was found to be the most risky model. The short dental arch case (M4) revealed the lowest stresses among the models but is not recommended when one more implant can be placed because of the bending forces that could occur at the mesial implant. In M2 and M3, the distal implants were placed bicortically between the crestal and sinus cortical plates, causing a fall of the stresses because of the bicortical stability of these implants.


[Comparative analysis for mental patients' life quality between developed and developing regions].
To explore the differences, causes and countermeasures for mental patients' life quality between developed and developing regions. Methods: Based on the Quality of Life Questionnaire for Psychiatric Patients (QOL-P) and adopting convenient random sampling method, a total of 340 mental patients in Shanghai and Guangxi were investigated, and the data were analyzed by methods of Paired Design Crosstabulation Data hypothesis test, multivariate logistic regression, and independent sample Kruskal-Wallis test. The differences in patients' life quality in the 2 regions and the influential factors were evaluated. Results: There were high consistency and correlation in the total scores of self-evaluation items G (self overall evaluation of life quality by patient) between the 2 regions. Region and gender significantly affected mental patients' life quality in the basic demography characteristics in the 2 regions. The differences between total scores of 4 independent samples grouped by region and sex were significant (P<0.01). The male and femal patients in Guangxi in the dimensions of physiology, psychology, society and symptom were better than those in Shanghai (P<0.01). There was certain homoplasy between the patients from Shanghai and those from Guangxi in terms of the most prominent matters that affect the mental patients' life quality, with the former being affected more seriously than the latter. Conclusion: To a certain extent, the mental patients' life quality in the developing region (Guangxi) is better than that in the developed region (Shanghai).


Intracellular analysis of excitatory-inhibitory synaptic interactions in crayfish stretch receptors.
1. To determine the membrane mechanisms underlying the interactions between inhibitory postsynaptic potentials (IPSPs) and excitatory inputs, we investigated, at the membrane potential level, the combined influences of low-frequency (0.05-0.50 Hz) imposed sinusoidal transmembrane currents (termed sine currents), representing the excitatory drive, and trains of regular (3-30/s) IPSPs. The two simplest possible neuron systems exemplified by the slowly and rapidly adapting stretch receptors of crayfish (RM1 and RM2, respectively) were used. 2. At constant elongation the RM1 and RM2 behaved as a pacemaker and a neuron without self-sustained oscillations, respectively, but in dynamic conditions uninhibited controls and IPSP sine current interactions were essentially identical in both RMs. Controls showed the usual smooth variation of the RM firing rate in response to the gradually varying excitatory input. IPSP effects were characterized by the expected overall reduction of the postsynaptic firing rate. More important, special effects were also present, such as the simple fixed alternations of IPSP and postsynaptic spikes (e.g., 1 IPSP, 1 postsynaptic or 1:1; 1 IPSP, 2 postsynaptic or 1:2; 2 IPSPs, 1 postsynaptic spike or 2:1), where interspike intervals were more constant than uninhibited controls and where the sensitivity to the excitatory input was reduced to small values, and the sudden firing rate discontinuities consisting of instantaneous discharge accelerations or decelerations (termed "jumps") between successive alteration ratios, where sensitivity increased to large values. Therefore with inhibition the RM firing rate varied discontinuously in response to the gradually changing input, and the discharge rate could take one of several discrete values by switching between different alteration ratios. 3. At the alternations the times elapsed between an IPSP and the closest spike before (phase, phi) or after it (cophase, theta) increased and decreased, respectively, with increasing excitation. The major membrane potential modification that accompanied the interactions at the alternations was the gradual increase of the post-IPSP slope as a function of excitatory drive, which reduced the time to reach the firing level or theta. 4. Inhibition introduced subtle and complex nonlinear modifications in the coding of convergent excitatory input. The most notable nonlinearity was the discontinuous variations of the firing rate as a function of the gradually changing excitatory input. Effects were due to voltage interactions occurring at the extrasynaptic membrane, with a decisive involvement of the spike generator and insignificant participation of the shunting action of IPSPs. The results provide yet another example of the predominant influence of intrinsic membrane properties in determining the effects of synaptic-evoked activity.(ABSTRACT TRUNCATED AT 400 WORDS)


Melatonin and ubiquitin: what's the connection?
Melatonin has been widely studied for its role in photoperiodism in seasonal breeders; it is also a potent antioxidant. Ubiquitin, a protein also widespread in living cells, contributes to many cellular events, although the most well known is that of tagging proteins for destruction by the proteasome. Herein, we suggest a model in which melatonin interacts with the ubiquitin-proteasome system to regulate a variety of seemingly unrelated processes. Ubiquitin, for example, is a major regulator of central activity of thyroid hormone type 2 deiodinase; the subsequent regulation of T3 may be central to the melatonin-induced changes in seasonal reproduction and seasonal changes in metabolism. Both melatonin and ubiquitin also have important roles in protecting cells from oxidative stress. We discuss the interaction of melatonin and the ubiquitin-proteasome system in oxidative stress through regulation of the ubiquitin-activating enzyme, E1. Previous reports have shown that glutathiolation of this enzyme protects proteins from unnecessary degradation. In addition, evidence is discussed concerning the interaction of ubiquitin and melatonin in activation of the transcription factor NF-κB as well as modulating cellular levels of numerous signal transducing factors including the tumor suppressor, p53. Some of the actions of melatonin on the regulatory particle of the proteasome appear to be related to its inhibition of the calcium-dependent calmodulin kinase II, an enzyme which reportedly copurifies with proteasomes. Many of the actions of melatonin on signal transduction are similar to those of a proteasome inhibitor. While these actions of melatonin could be explained by a direct inhibitory action on the catalytic core particle of the proteasome, this has not been experimentally verified. If our hypothesis of melatonin as a general inhibitor of the ubiquitin-proteasome system is confirmed, it is predicted that more examples of this interaction will be demonstrated in a variety of tissues in which ubiquitin and melatonin co-exist. Furthermore, the hypothesis of melatonin as an inhibitor of the ubiquitin-proteasome system will be a very useful model for clinical testing of melatonin.


Seroprevalence of Toxoplasma gondii and Neospora caninum in dogs from Korea.
Toxoplasma gondii and Neospora caninum are closely related protozoan parasites, they share many common hosts, and can cause neurological diseases in dogs. Dogs can have close contacts with humans and livestock and therefore they can act as reservoirs of these parasites. The aim of this study was to survey the seroprevalence of antibodies against T. gondii and N. caninum and their co-infection rate in dogs in Korea. In total, sera from 553 domestic dogs were collected from different breeds, sexes, and ages of dogs from nine provinces across the country of Korea during 2006 and 2007. The presence of antibodies against T. gondii and N. caninum was analyzed using the latex agglutination test (LAT) with a cut-off value of 1:32, and the indirect fluorescent antibody test (IFAT) using a serum titer of 1:100. In the total dog population, 71 (12.8%) dogs were positive for anti-T. gondii antibodies and only 20 (3.6%) were positive for anti-N. caninum antibodies. Relatively higher seropositive frequencies of antibodies against T. gondii (20.1%) and N. caninum (4.9%) were detected in the dog population from the Gyeonggi. A higher proportion of animals seropositive for anti-T. gondii antibodies was found in stray dog populations as compared to household dog populations: 18.5% (59/319) vs 5.1% (12/234), respectively. The Chi-square tests revealed significant differences in the seropositive frequencies of antibodies against T. gondii between stray and household dogs in the total population (p<0.0001), and in dogs from the Gyeonggi (p<0.01). No significant differences were observed for the presence of antibodies against T. gondii or N. caninum when compared across the sex or age (p>0.05). The first serological survey on antibodies against both T. gondii and N. caninum parasites across the entire country showed that co-infection was not common in these canine populations with a seropositive level of 0.72%. The significantly higher positive frequency of T. gondii antibodies in stray dogs in both, Gyeonggi and in the total dog populations suggests that further investigation on the seroprevalence of parasites should focus on stray dogs.


Identification of helper T cell master regulator candidates using the polar score method.
The T helper paradigm is currently being revised from the Th1-Th2 dichotomy to a multi-state paradigm involving a number of different cell phenotypes. Transcriptional profiling using microarrays has been used to study the development of these phenotypes. There is however no clear consensus on how to approach the analysis of this data, especially in the context of cells that are triggered to expand rapidly, and massively change their gene expression pattern. We develop a method we call 'polar score' to identify genes that are related to T helper cell polarization. This method is designed to identify polarizing genes in a set where many genes change expression. To illustrate the use of this technique, we apply it to published T cell microarray data and compare it to conventional analysis methods. With the new method, we find evidence for the existence of IL9 producing T cells ('Th9 cells') that are induced by a combination of TGFβ and IL4. We identify several candidate master regulator genes for this phenotype. Furthermore, treatment with TGFβ and IL12 results in a Treg and Th17 hybrid cell phenotype.


Ulex Europaeus Agglutinin-1 Is a Reliable Taste Bud Marker for In Situ Hybridization Analyses.
Taste signals are received by taste buds. To better understand the taste reception system, expression patterns of taste-related molecules are determined by in situ hybridization (ISH) analyses at the histological level. Nevertheless, even though ISH is essential for determining mRNA expression, few taste bud markers can be applied together with ISH. Ulex europaeus agglutinin-1 (UEA-1) appears to be a reliable murine taste bud marker based on immunohistochemistry (IHC) analyses. However, there is no evidence as to whether UEA-1 can be used for ISH. Thus, the present study evaluated UEA-1 using various histochemical methods, especially ISH. When lectin staining was performed after ISH procedures, UEA-1 clearly labeled taste cellular membranes and distinctly indicated boundaries between taste buds and the surrounding epithelial cells. Additionally, UEA-1 was determined as a taste bud marker not only when used in single-colored ISH but also when employed with double-labeled ISH or during simultaneous detection using IHC and ISH methods. These results suggest that UEA-1 is a useful marker when conducting analyses based on ISH methods. To clarify UEA-1 staining details, multi-fluorescent IHC (together with UEA-1 staining) was examined, resulting in more than 99% of cells being labeled by UEA-1 and overlapping with KCNQ1-expressing cells.


An alternative leukocyte homotypic adhesion mechanism, LFA-1/ICAM-1-independent, triggered through the human VLA-4 integrin.
The VLA-4 (CD49d/CD29) integrin is the only member of the VLA family expressed by resting lymphoid cells that has been involved in cell-cell adhesive interactions. We here describe the triggering of homotypic cell aggregation of peripheral blood T lymphocytes and myelomonocytic cells by mAbs specific for certain epitopes of the human VLA alpha 4 subunit. This anti-VLA-4-induced cell adhesion is isotype and Fc independent. Similar to phorbol ester-induced homotypic adhesion, cell aggregation triggered through VLA-4 requires the presence of divalent cations, integrity of cytoskeleton and active metabolism. However, both adhesion phenomena differed at their kinetics and temperature requirements. Moreover, cell adhesion triggered through VLA-4 cannot be inhibited by cell preincubation with anti-LFA-1 alpha (CD11a), LFA-1 beta (CD18), or ICAM-1 (CD54) mAb as opposed to that mediated by phorbol esters, indicating that it is a LFA-1/ICAM-1 independent process. Antibodies specific for CD2 or LFA-3 (CD58) did not affect the VLA-4-mediated cell adhesion. The ability to inhibit this aggregation by other anti-VLA-4-specific antibodies recognizing epitopes on either the VLA alpha 4 (CD49d) or beta (CD29) chains suggests that VLA-4 is directly involved in the adhesion process. Furthermore, the simultaneous binding of a pair of aggregation-inducing mAbs specific for distinct antigenic sites on the alpha 4 chain resulted in the abrogation of cell aggregation. These results indicate that VLA-4-mediated aggregation may constitute a novel leukocyte adhesion pathway.


Implications of urbanization for artisanal parrotfish fisheries in the Western Solomon Islands.
Increasing migration into urbanized centers in the Solomon Islands poses a great threat to adjacent coral reef fisheries because of negative effects on the fisheries and because it further erodes customary management systems. Parrotfish fisheries are of particular importance because the feeding habits of parrotfish (scrape and excavate coral) are thought to be critical to the resilience of coral reefs and to maintaining coral reef health within marine protected areas. We investigated the ecological impact of localized subsistence and artisanal fishing pressure on parrotfish fisheries in Gizo Town, Western Solomon Islands, by analyzing the density and size distribution of parrotfish with an underwater visual census (UVC), recall diary (i.e., interviews with fishers), and creel surveys to independently assess changes in abundance and catch-per-unit-effort (CPUE) over 2 years. We then compared parrotfish data from Gizo Town with equivalent data from sites open to and closed to fishing in Kida and Nusa Hope villages, which have different customary management regimes. Results indicated a gradient of customary management effectiveness. Parrotfish abundance was greater in customary management areas closed to fishing, especially with regard to larger fish sizes, than in areas open to fishing. The decline in parrotfish abundance from 2004 to 2005 in Gizo was roughly the same magnitude as the difference in abundance decline between inside and outside customary management marine reserves. Our results highlight how weak forms of customary management can result in the rapid decline of vulnerable fisheries around urbanized regions, and we present examples in which working customary management systems (Kinda and Nusa Hope) can positively affect the conservation of parrotfish--and reef fisheries in general--in the highly biodiverse Coral Triangle region.


Pseudomembranous colitis: spectrum of imaging findings with clinical and pathologic correlation.
Pseudomembranous colitis (PMC) is a potentially life-threatening acute infectious colitis caused by one or more toxins produced by an unopposed proliferation of Clostridium difficile bacteria. PMC is characterized by the presence of elevated, yellow-white plaques forming pseudomembranes on the colonic mucosa. These plaques can be visualized at both pathologic analysis and endoscopy. Plain radiography, contrast enema studies, and computed tomography (CT) are useful in the evaluation of PMC. Plain radiography of the abdomen can demonstrate polypoid mucosal thickening, "thumbprinting" (wide transverse bands associated with haustral fold thickening), or gaseous distention of the colon. A toxic megacolon with distention and occasionally pneumoperitoneum may be seen in the most severe cases of PMC involving perforation. At contrast enema studies, the primary finding in mild cases of PMC is small nodular filling defects representing the mucosal plaques. With more extensive colonic involvement, the plaques are larger and coalesce to form an irregular bowel wall margin. Mural thickening and wide haustral folds caused by intramural edema may also be seen. A contrast enema study is contraindicated in patients with severe PMC due to the danger of perforation. Common CT findings include wall thickening, low-attenuation mural thickening corresponding to mucosal and submucosal edema, the "accordion sign," the "target sign" ("double halo sign"), pericolonic stranding, and ascites. Familiarity with these imaging characteristics may allow early diagnosis and treatment and prevent progression to more serious pathologic conditions.


Charcot-Marie-Tooth disease associated with hypertrophic neuropathy: a neuropathologic study of two cases.
The neuropathologic features of two cases of Charcot-Marie-Tooth disease associated with hypertrophic neuropathy are described. The peripheral nerves had a loss of myelinated fibers, endoneurial fibrosis, and numerous onion-bulb formations. The most severe changes were seen in the distal nerves. In the older of the two patients, advanced changes were also observed in the proximal nerves and anterior roots and were associated with neuronal degeneration in the anterior horns and dorsal root ganglia. The muscles were the site of chronic denervation atrophy, which was most severe in the distal portions of the lower extremities. In one of the cases, the autopsy findings were complemented by sural nerve biopsy studies, which confirmed the presence of segmental demyelination and remyelination, axonal degeneration, and Schwann cell proliferation in the form of onion bulbs. Our observations support the concept of a primary neuronal abnormality in the hypertrophic type of Charcot-Marie-Tooth disease (HN-CMT). The disorder appears to initially involve the distal axonal processes but, with progression of the disease, also involves the proximal axons, eventually leading to degeneration and loss of neurons in the anterior horns and dorsal root ganglia. Onion-bulb formation generally parallels nerve fiber degeneration, suggesting that segmental demyelination and onion bulbs may occur secondary to axonal degeneration. The possibility of a concomitant Schwann cell abnormality cannot be excluded, however, on the basis of our postmortem studies.


Protein synthesis inhibitors attenuate water flow in vasopressin-stimulated toad urinary bladder.
Vasopressin stimulates the introduction of aggregated particles, which may represent pathways for water flow, into the luminal membrane of toad urinary bladder. It is not known whether water transport pathways are degraded on removal from membrane or whether they are recycled. We examined the effect of the protein synthesis inhibitors cycloheximide and puromycin using repeated 30-min cycles of vasopressin followed by washout of vasopressin, all in the presence of an osmotic gradient, a protocol that maximizes aggregate turnover. "High dose" cycloheximide (200 micrograms/ml) inhibited flow immediately. "Low dose" cycloheximide (1 microgram/ml) did not affect initial flow; however, flow was inhibited by the fourth restimulation. On further rechallenge, inhibition persisted but did not increase. In the absence of vasopressin, inhibition did not develop. Despite the inhibition of flow in vasopressin-treated tissues, the cAMP-dependent protein kinase ratio (-cAMP/+cAMP), an index of in vivo cAMP effect, was elevated in cycloheximide-treated tissues, suggesting modulation at a distal site in the stimulatory cascade. Cycloheximide inhibited flow when 10 microM forskolin or 0.2 mM 8-BrcAMP was substituted for vasopressin in the fourth period; however, MIX (4 mM)-stimulated flow was enhanced by 1 microgram/ml cycloheximide but inhibited by 200 micrograms/ml cycloheximide. [14C]urea permeability was not inhibited by cycloheximide. Puromycin (0.5 mM) also inhibited water flow by the fourth challenge with vasopressin. The data suggest that protein synthesis inhibitors attenuate flow at a site that is distal to cAMP-dependent protein kinase.(ABSTRACT TRUNCATED AT 250 WORDS)


Prolactin and teleost ionocytes: new insights into cellular and molecular targets of prolactin in vertebrate epithelia.
The peptide hormone prolactin is a functionally versatile hormone produced by the vertebrate pituitary. Comparative studies over the last six decades have revealed that a conserved function for prolactin across vertebrates is the regulation of ion and water transport in a variety of tissues including those responsible for whole-organism ion homeostasis. In teleost fishes, prolactin was identified as the "freshwater-adapting hormone", promoting ion-conserving and water-secreting processes by acting on the gill, kidney, gut and urinary bladder. In mammals, prolactin is known to regulate renal, intestinal, mammary and amniotic epithelia, with dysfunction linked to hypogonadism, infertility, and metabolic disorders. Until recently, our understanding of the cellular mechanisms of prolactin action in fishes has been hampered by a paucity of molecular tools to define and study ionocytes, specialized cells that control active ion transport across branchial and epidermal epithelia. Here we review work in teleost models indicating that prolactin regulates ion balance through action on ion transporters, tight-junction proteins, and water channels in ionocytes, and discuss recent advances in our understanding of ionocyte function in the genetically and embryonically accessible zebrafish (Danio rerio). Given the high degree of evolutionary conservation in endocrine and osmoregulatory systems, these studies in teleost models are contributing novel mechanistic insight into how prolactin participates in the development, function, and dysfunction of osmoregulatory systems across the vertebrate lineage.


Cardiovascular and Interventional Radiological Society of Europe commentary on the treatment of chronic cerebrospinal venous insufficiency.
Chronic cerebrospinal venous insufficiency (CCSVI) is a putative new theory that has been suggested by some to have a direct causative relation with the symptomatology associated with multiple sclerosis (MS) [1]. The core foundation of this theory is that there is abnormal venous drainage from the brain due to outflow obstruction in the draining jugular vein and/or azygos veins. This abnormal venous drainage, which is characterised by special ultrasound criteria, called the "venous hemodynamic insufficiency severity score" (VHISS), is said to cause intracerebral flow disturbance or outflow problems that lead to periventricular deposits [2]. In the CCSVI theory, these deposits have a great similarity to the iron deposits seen around the veins in the legs in patients with chronic deep vein thrombosis. Zamboni, who first described this new theory, has promoted balloon dilatation to treat the outflow problems, thereby curing CCSVI and by the same token alleviating MS complaints. However, this theory does not fit into the existing bulk of scientific data concerning the pathophysiology of MS. In contrast, there is increasing worldwide acceptance of CCSVI and the associated balloon dilatation treatment, even though there is no supporting scientific evidence. Furthermore, most of the information we have comes from one source only. The treatment is called "liberation treatment," and the results of the treatment can be watched on YouTube. There are well-documented testimonies by MS patients who have gained improvement in their personal quality of life (QOL) after treatment. However, there are no data available from patients who underwent unsuccessful treatments with which to obtain a more balanced view. The current forum for the reporting of success in treating CCSVI and thus MS seems to be the Internet. At the CIRCE office and the MS Centre in Amsterdam, we receive approximately 10 to 20 inquiries a month about this treatment. In addition, many interventional radiologists, who are directly approached by MS patients, contact the Cardiovascular and Interventional Radiological Society of Europe (CIRSE) for advice. Worldwide, several centres are actively promoting and performing balloon dilatation, with or without stenting, for CCSVI. Thus far, no trial data are available, and there is currently no randomized controlled trial (RCT) in progress Therefore, the basis for this new treatment rests on anecdotal evidence and successful testimonies by patients on the Internet. CIRSE believes that this is not a sound basis on which to offer a new treatment, which could have possible procedure-related complications, to an often desperate patient population.


Resveratrol Protects Hippocampal Astrocytes Against LPS-Induced Neurotoxicity Through HO-1, p38 and ERK Pathways.
Resveratrol, a phytoalexin found in grapes and wine, exhibits antioxidant, anti-inflammatory, anti-aging and antitumor activities. Resveratrol also protects neurons and astrocytes in several neurological disease models. Astrocytes are responsible for modulating neurotransmitter systems, synaptic information, ionic homeostasis, energy metabolism, antioxidant defense and inflammatory response. In previous work, we showed that resveratrol modulates important glial functions, including glutamate uptake, glutamine synthetase activity, glutathione (GSH) levels and inflammatory response. Furthermore, astrocytes express toll-like receptors that specifically recognize lipopolysaccharide (LPS), which has been widely used to study experimentally inflammatory response. In this sense, LPS may stimulate pro-inflammatory cytokines release and oxidative stress. Moreover, there is interplay between these signals through signaling pathways such as NFκB, HO-1 and MAPK. Thus, here, we evaluated the effects of resveratrol on LPS-stimulated inflammatory response in hippocampal primary astrocyte cultures and the putative role of HO-1, p38 and ERK pathways in the protective effect of resveratrol. LPS increased the levels of TNF-α, IL-1β, IL-6 and IL-18 and resveratrol prevented these effects. Resveratrol also prevented the oxidative and nitrosative stress induced by LPS as well as the decrease in GSH content. Additionally, we demonstrated the involvement of NFκB, HO-1, p38 and ERK signaling pathways in the protective effect of resveratrol, providing the first mechanistic explanation for these effects in hippocampal astrocytes. Our findings reinforce the neuroprotective effects of resveratrol, which are mainly associated with anti-inflammatory and antioxidant activities.


Indole carboxamides inhibit bovine testes hyaluronidase at pH 7.0 and indole acetamides activate the enzyme at pH 3.5 by different mechanisms.
Hyaluronidases are enzymes controlling many crucial physiological processes. Imbalanced enzymatic activity is connected with severe diseases. Because there is limited availability of drugs modulating hyaluronidase activity, the search for hyaluronidase interacting compounds is getting more and more important. A series of fifteen indole carboxamides and acetamides were synthesized and tested on inhibition of bovine testes hyaluronidase. In vitro assays were performed using stains-all at pH 7 and the Morgan-Elson reaction at pH 3.5. At neutral pH, the most active inhibitory compound was N-(Pyridin-4yl)-[5-bromo-1-(4-fluorobenzyl)indole-3-yl]carboxamide (20) with an IC(50) value of 46 microM. Surprisingly, inhibition of all compounds was completely abolished by a decrease in pH. At pH 3.5 the activity of the enzyme was increased up to 134% by compound N-(4,6-Dimethylpyridin-2yl)-(1-ethylindole-3-yl)acetamide (24) at a concentration of 100 microM. The known activating effect of bovine serum albumine (BSA) on hyaluronidase activity was verified in the assay and compared to the effect of compound 24. Structure-activity relationships are discussed and a model is proposed, which explains the increase in activity at pH 3.5 by bonding of the protonated form of N-(4,6-Dimethylpyridin-2yl)-(1-ethylindole-3-yl)acetamide (24) to hyaluronic acid. The bonding results in an elongated form of the substrate with easier enzymatic access.


Higher maternal serum prolactin levels are associated with reduced glucose tolerance during pregnancy.
It is unknown if high prolactin levels during pregnancy contribute to the development of gestational diabetes. We hypothesized that higher prolactin levels are associated with reduced glucose tolerance, as determined by higher 2-h glucose level from an oral glucose tolerance test in pregnancy. The 75-g oral glucose tolerance test was carried out at 28 weeks of gestation in 69 participants. A multiple regression analysis was used to determine the relationship between serum prolactin and 2-h glucose levels. Multivariable regression analysis showed an independent and significant relationship between third trimester prolactin and 2-h glucose levels post oral glucose tolerance test. Higher prolactin levels were associated with higher glucose levels independent of age, body mass index, gravidity and parity. Higher prolactin levels associated with reduced glucose tolerance in the third trimester of pregnancy suggests the possible independent role of prolactin in the pathogenesis of gestational diabetes.


Thoughts on the assessment of the DSM-5 alternative model for personality disorders: Comment on Sleep et al. (2019).
In a recent article, Sleep, Lynam, Widiger, Crowe, and Miller (2019) examined various properties of measures of Criterion A and Criterion B of the Alternative Model for Personality Disorders presented in DSM-5. This commentary discusses the suitability of certain indicators of factor structure, discriminant validity, and incremental validity as evaluative metrics for the assessment of personality disorder, both in general and as applied in that specific study. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Nutritional challenges and opportunities during the weaning period and in young childhood.
The early years of life are a period of very rapid growth and development. In this critical phase, food preferences are formed which carry over into childhood and beyond and foundations are laid for a healthy adult life. Excess energy, imbalances in macronutrient quality, and nutritional deficiencies may form inappropriate nutritional signals, leading to metabolic disturbances and affecting the obesity risk. For instance, the intake of protein and sugar-sweetened beverages in young children has been associated with an increased risk of overweight and obesity. In reality, scientific reports have shown that the dietary intakes of vegetables, α-linolenic acid, docosahexaenoic acid, iron, vitamin D, and iodine are low and the intakes of protein, saturated fatty acids, and added sugar are high in young children living in Europe. A focus on improving feeding habits and approaches to support more balanced nutritional intakes early in life may have significant public health benefits.


Mannose-binding lectin is a disease modifier in clinical malaria and may function as opsonin for Plasmodium falciparum-infected erythrocytes.
Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL to the membrane of P. falciparum-infected erythrocytes, which could be inhibited by mannose, was observed. Further characterization revealed that MBL reacted with a P. falciparum glycoprotein identical to the 78-kDa glucose-regulated stress protein of P. falciparum. MBL seems to be a disease modifier in clinical malaria and to function as an opsonin for erythrocytes invaded by P. falciparum and may thus be involved in sequestration of the parasite, which in turn may explain the association between homozygosity for MBL variant alleles and high parasite counts.


A Critical Analysis of the Drivers of Human Migration Patterns in the Presence of Climate Change: A New Conceptual Model.
Both climate change and migration present key concerns for global health progress. Despite this, a transparent method for identifying and understanding the relationship between climate change, migration and other contextual factors remains a knowledge gap. Existing conceptual models are useful in understanding the complexities of climate migration, but provide varying degrees of applicability to quantitative studies, resulting in non-homogenous transferability of knowledge in this important area. This paper attempts to provide a critical review of climate migration literature, as well as presenting a new conceptual model for the identification of the drivers of migration in the context of climate change. It focuses on the interactions and the dynamics of drivers over time, space and society. Through systematic, pan-disciplinary and homogenous application of theory to different geographical contexts, we aim to improve understanding of the impacts of climate change on migration. A brief case study of Malawi is provided to demonstrate how this global conceptual model can be applied into local contextual scenarios. In doing so, we hope to provide insights that help in the more homogenous applications of conceptual frameworks for this area and more generally.


Blood product transfusion in the critical care setting.
The past two decades have witnessed an extensive re-evaluation of transfusion therapy in the intensive care unit (ICU). The purpose of this review is to present the current state of knowledge regarding blood transfusion in the critically ill and to identify gaps in our current understanding for future research. Accumulating evidence suggests a lack of efficacy with red blood cell (RBC), plasma, and platelet transfusion in the majority of critically ill patients. Evidence has also increasingly exposed previously under-recognized transfusion risks. The result is a growing number of recommendations for more restrictive RBC, plasma, and platelet transfusion strategies. An important exception to a more conservative transfusion practice occurs in patients with major trauma and life-threatening bleeding. Delaying RBCs, plasma and platelet component therapies in this population can promote the lethal triad of coagulopathy, acidosis, and hypothermia with a resultant increase in bleeding, greater transfusion requirements, and higher mortality. Although we have made substantial progress in understanding the role of blood transfusion in the ICU, multiple important knowledge gaps persist. Future studies are needed to better define and characterize the impact of RBC storage, male-only plasma and platelet donor procurement procedures, and transfusion strategies in those requiring massive transfusion and with acute local or global tissue ischemia.


Vibrio aestuarianus subsp. cardii subsp. nov., pathogenic to the edible cockles Cerastoderma edule in France, and establishment of Vibrio aestuarianus subsp. aestuarianus subsp. nov. and Vibrio aestuarianus subsp. francensis subsp. nov.
Cockle mortality events have been reported in northern France since 2012. In the present study, we describe and investigate the implication of a potential bacterial causative agent in cockle mortality. Bacteria isolated from five different cockle mortality events were characterized and studied. Using phenotypic analysis combined with DNA-DNA hybridization (DDH) and whole genome sequencing, the isolates were shown to belong to Vibrio aestuarianus, a species regularly detected in France during oyster mortality events. Comparison of the strains from cockles with strains from French oysters and the type strain showed that the strains from cockles were genetically different to those from oysters and also different to the V. aestuarianus type strain. Moreover, the cockle and oyster strains were classified into two different, but close, groups both separated from the type strain by: (1) analyses of the ldh gene sequences; (2) DDH assays between 12/122 3T3T (LMG 31436T=DSM 109723T), a representative cockle strain, 02/041T (CIP 109791T=LMG 24517T) representative oyster strain and V. aestuarianus type strain LMG 7909T; (3) average nucleotide identity values calculated on the genomes; and (4) phenotypic traits. Finally, results of MALDI-TOF analyses also revealed specific peaks discriminating the three representative strains. The toxicity of representative strains of these cockle isolates was demonstrated by experimental infection of hatchery-produced cockles. The data therefore allow us to propose two novel subspecies of Vibrio aestuarianus: Vibrio aestuarianus subsp. cardii subsp. nov. for the cockle strains and Vibrio aestuarianus subsp. francensis subsp. nov. for the Pacific oyster strains, in addition to an emended description of the species Vibrio aestuarianus.


Impact of Sugammadex Versus Neostigmine/Glycopyrrolate on Perioperative Efficiency.
Neuromuscular blockade in the operating room necessitates the utilization of reversal agents to accelerate postoperative recovery and sustain operating room patient throughput. Cholinesterase inhibitors represent the historical standard of care for neuromuscular blockade reversal within anesthesia practice. Sugammadex, a synthetic gamma-cyclodextrin, was introduced to the market with evidence of more rapid and predictable reversal of neuromuscular blockade compared to alternative agents. Higher medication acquisition costs have limited more extensive use of sugammadex compared to that of neostigmine/glycopyrrolate. The purpose of this study was to examine the impact of sugammadex versus neostigmine/glycopyrrolate on perioperative efficiency to validate medication acquisition cost value. A retrospective investigation was performed of patients with a surgical procedure at Houston Methodist Hospital from July 31, 2017 through August 1, 2018. The primary endpoint was time from reversal medication administration to operating room exit. Patient-specific doses were assessed to calculate average medication acquisition costs. The economic benefits of sugammadex were measured through review of average operating room and postanesthesia care unit costs per minute. There were a total of 640 surgical cases at Houston Methodist Hospital eligible for inclusion into the research study. The time from medication administration to operating room exit was significantly faster for sugammadex compared to neostigmine/glycopyrrolate (P<0.001) upon univariate analysis. However, when measured with linear regression, the difference in operating room exit time between sugammadex and neostigmine/glycopyrrolate was no longer statistically significant (P=0.122). Medication acquisition cost review highlighted a difference of $178.20, favoring use of neostigmine/glycopyrrolate. The utilization of sugammadex does not correlate to consequential time saved in the operating room or extrapolation to workflow capacity for increased surgical case volume. Consideration of the medication acquisition cost promotes more restrictive use of sugammadex to indications with clinical relevance.


Further observations on the presence of wandering phagocytes within the teleostean retina.
A previous report by this author has noted the presence of wandering phagocytes at the photo-receptor-retinal epithelial interface in five teleostean species. A further 5 species have now been investigated by electron microscopy and again all specimens examined consistently show the presence of this population of phagocytes. The new species studied are the goldeye (Hiodon alosoides), the yellow eel (Anguilla anguilla), the archer fish (Toxotes jaculatrix), the goldfish (Carassius auratus) and the burbot (Lota lota). A population of ameboid phagocytes appears to be a normal feature of the teleostean retina. In some species (i.e., the goldeye and the goldfish) the phagocytes were extremely numerous and could be located in groups of 20-25. In addition, preliminary experiments with the goldfish have shown that these wandering phagocytes undergo a cyclic pattern to show changes in both morphology and location dependent upon environmental lighting.


The plant-associated bacterium Stenotrophomonas rhizophila expresses a new enzyme for the synthesis of the compatible solute glucosylglycerol.
The rhizobacterium Stenotrophomonas rhizophila accumulates the compatible solutes glucosylglycerol (GG) and trehalose under salt stress conditions. The complete gene for the GG synthesis enzyme was cloned and sequenced. This enzyme from S. rhizophila represented a novel fusion protein composed of a putative C-terminal GG-phosphate synthase domain and an N-terminal putative GG-phosphate phosphatase domain, which was named GgpPS. A similar gene was cloned from Pseudomonas sp. strain OA146. The ggpPS gene was induced after a salt shock in S. rhizophila cells. After the salt-loaded cells reached stationary phase, the ggpPS mRNA content returned to the low level characteristic of the control cells, and GG was released into the medium. The complete ggpPS gene and a truncated version devoid of the phosphatase part were obtained as recombinant proteins. Enzyme activity tests revealed the expected abilities of the full-length protein to synthesize GG and the truncated GgpPS to synthesize GG-phosphate. However, dephosphorylation of GG-phosphate was detected only with the complete GgpPS protein. These enzyme activities were confirmed by complementation experiments using defined GG-defective mutants of the cyanobacterium Synechocystis sp. strain PCC 6803. Genes coding for proteins very similar to the newly identified fusion protein GgpPS for GG synthesis in S. rhizophila were found in genome sequences of related bacteria, where these genes are often linked to a gene coding for a transporter of the Mfs superfamily.


Syndecan-4 regulates early neutrophil migration and pulmonary inflammation in response to lipopolysaccharide.
Proteoglycans (PGs) and their associated glycosaminoglycan side chains are effectors of inflammation, but little is known about changes to the composition of PGs in response to lung infection or injury. The goals of this study were to identify changes to heparan sulfate PGs in a mouse model of gram-negative pneumonia, to identify the Toll-like receptor adaptor molecules responsible for these changes, and to determine the role of the heparan sulfate PG in the innate immune response in the lungs. We treated mice with intratracheal LPS, a component of the cell wall of gram-negative bacteria, to model gram-negative pneumonia. Mice treated with intratracheal LPS had a rapid and selective increase in syndecan-4 mRNA that was regulated through MyD88-dependent mechanisms, whereas expression of several other PGs was not affected. To determine the role of syndecan-4 in the inflammatory response, we exposed mice deficient in syndecan-4 to LPS and found a significant increase in neutrophil numbers and amounts of CXC-chemokines and total protein in bronchoalveolar lavage fluid. In studies performed in vitro, macrophages and epithelial cells treated with LPS had increased expression of syndecan-4. Studies performed using BEAS-2B cells showed that pretreatment with heparin and syndecan-4 decreased the expression of CXCL8 mRNA in response to LPS and TNF-α. These findings indicate that the early inflammatory response to LPS involves marked up-regulation of syndecan-4, which functions to limit the extent of pulmonary inflammation and lung injury.


A Web-Based Photo-Alteration Intervention to Promote Sleep: Randomized Controlled Trial.
Receiving insufficient sleep has wide-ranging consequences for health and well-being. Although educational programs have been developed to promote sleep, these have had limited success in extending sleep duration. To address this gap, we developed a Web-based program emphasizing how physical appearances change with varying amounts of sleep. The aims of this study were to evaluate (1) whether participants can detect changes in appearances as a function of sleep and (2) whether this intervention can alter habitual sleep patterns. We conducted a 5-week, parallel-group, randomized controlled trial among 70 habitual short sleepers (healthy adults who reported having <7 hours of sleep routinely). Upon study enrollment, participants were randomly assigned (1:1) to receive either standard information or an appearance-based intervention. Both groups received educational materials about sleep, but those in the appearance group also viewed a website containing digitally edited photographs that showed how they would look with varying amounts of sleep. As the outcome variables, sleep duration was monitored objectively via actigraphy (at baseline and at postintervention weeks 1 and 4), and participants completed a measure of sleep hygiene (at baseline and at postintervention weeks 2, 4, and 5). For each outcome, we ran intention-to-treat analyses using linear mixed-effects models. In total, 35 participants were assigned to each group. Validating the intervention, participants in the appearance group (1) were able to identify what they looked like at baseline and (2) judged that they would look more attractive with a longer sleep duration (t26=10.35, P<.001). In turn, this translated to changes in sleep hygiene. Whereas participants in the appearance group showed improvements following the intervention (F1,107.99=9.05, P=.003), those in the information group did not (F1,84.7=0.19, P=.66). Finally, there was no significant effect of group nor interaction of group and time on actigraphy-measured sleep duration (smallest P=.26). Our findings suggest that an appearance-based intervention, while not sufficient as a stand-alone, could have an adjunctive role in sleep promotion. ClinicalTrials.gov NCT02491138; https://clinicaltrials.gov/ct2/show/study/NCT02491138.


Cell cycle-dependent variations in c-Jun and JunB phosphorylation: a role in the control of cyclin D1 expression.
The transcription factor AP-1, composed of Jun and Fos proteins, is a major target of mitogen-activated signal transduction pathways. However, little is known about AP-1 function in normal cycling cells. Here we report that the quantity and the phosphorylation state of the c-Jun and JunB proteins vary at the M-G(1) transition. Phosphorylation of JunB by the p34(cdc2)-cyclin B kinase is associated with lower JunB protein levels in mitotic and early G(1) cells. In contrast, c-Jun levels remain constant while the protein undergoes N-terminal phosphorylation, increasing its transactivation potential. Since JunB represses and c-Jun activates the cyclin D1 promoter, these modifications of AP-1 activity during the M-G(1) transition could provide an impetus for G(1) progression by a temporal increase in cyclin D1 transcription. These findings constitute a novel example of a reciprocal connection between transcription factors and the cell cycle machinery.


The spatial relationship between traffic-related air pollution and noise in two Danish cities: Implications for health-related studies.
Air pollution and noise originating from urban road traffic have been linked to the adverse health effects e.g. cardiovascular disease (CVD), although their generation and propagation mechanisms vary. We aimed to (i) develop a tool to model exposures to air pollution and noise using harmonized inputs based on similar geographical structure (ii) explore the relationship (using Spearman's rank correlation) of both pollutions at residential exposure level (iii) investigate the influence of traffic speed and Annual Average Daily Traffic (AADT) on air-noise relationship. The annual average (2005) air pollution (NOx, NO2, PM10, PM2.5) and noise levels (Lday, Leve, Lnight, Lden, LAeq,24h) are modelled at address locations in Copenhagen and Roskilde (N = 11,000 and 1500). The new AirGIS system together with the Operational Street Pollution Model (OSPM®) is used to produce air pollution estimates. Whereas, noise is estimated using Common Noise Assessment Methods in the EU (CNOSSOS-EU, hereafter CNOSSOS) with relatively coarser inputs (100 m CORINE land cover, simplified vehicle composition). In addition, noise estimates (Lday, Leve, Lnight) from CNOSSOS are also compared with noise estimates from Road Traffic Noise 1996 (RTN-96, one of the Nordic noise prediction standards). The overall air-noise correlation structure varied significantly in the range |rS| = 0.01-0.42, which was mainly affected by the background concentrations of air pollution as well as non-traffic emission sources. Moreover, neither AADT nor traffic speed showed substantial influence on the air-noise relationship. The noise levels estimated by CNOSSOS were substantially lower, and showed much lower variation than levels obtained by RTN-96. CNOSSOS, therefore, needs to be further evaluated using more detailed inputs (e.g. 10 m land cover polygons) to assess its feasibility for epidemiological noise exposure studies in Denmark. Lower to moderate air-noise correlations point towards significant potential to determine the independent health effects of air pollution and noise.


Transplantation and survival of mouse inner ear progenitor/stem cells in the organ of Corti after cochleostomy of hearing-impaired guinea pigs: preliminary results.
In mammals, damage to sensory receptor cells (hair cells) of the inner ear results in permanent sensorineural hearing loss. Here, we investigated whether postnatal mouse inner ear progenitor/stem cells (mIESCs) are viable after transplantation into the basal turns of neomycin-injured guinea pig cochleas. We also examined the effects of mIESC transplantation on auditory functions. Eight adult female Cavia porcellus guinea pigs (250-350 g) were deafened by intratympanic neomycin delivery. After 7 days, the animals were randomly divided in two groups. The study group (n=4) received transplantation of LacZ-positive mIESCs in culture medium into the scala tympani. The control group (n=4) received culture medium only. At 2 weeks after transplantation, functional analyses were performed by auditory brainstem response measurement, and the animals were sacrificed. The presence of mIESCs was evaluated by immunohistochemistry of sections of the cochlea from the study group. Non-parametric tests were used for statistical analysis of the data. Intratympanic neomycin delivery damaged hair cells and increased auditory thresholds prior to cell transplantation. There were no significant differences between auditory brainstem thresholds before and after transplantation in individual guinea pigs. Some mIESCs were observed in all scalae of the basal turns of the injured cochleas, and a proportion of these cells expressed the hair cell marker myosin VIIa. Some transplanted mIESCs engrafted in the cochlear basilar membrane. Our study demonstrates that transplanted cells survived and engrafted in the organ of Corti after cochleostomy.


Fe3O4/carbon-decorated graphene boosts photothermal conversion and storage of phase change materials.
Pristine organic phase change materials (PCMs) are difficult to complete photothermal conversion and storage. To upgrade their photothermal conversion and storage capacity, we developed Fe-MOF (metal-organic framework) derived Fe3O4/C-decorated graphene (GP) based composite PCMs toward solar energy harvesting. Graphene is an excellent phonon conductor, and Fe3O4/C-GP as a photon capturer exhibits strong full-spectrum absorption. Additionally, Fe-MOF derived Fe3O4 nanoparticles are anchored on graphene nanosheets to reduce interfacial thermal resistance, shorten thermal diffusion path, and accelerate phonon transport. After the encapsulation of octadecanol (ODA) in Fe3O4/C-GP, ODA@Fe3O4/C-GP composite PCMs yield a high photothermal conversion efficiency of 88.18 % under 0.12 W/cm2 benefiting from the synergistic effect of 3D interconnected graphene framework and Fe3O4 nanoparticles with localized surface plasmon resonance effect. Moreover, ODA@Fe3O4/C-GP composite PCMs exhibit excellent latent heat storage stability, photothermal conversion stability and durable reliability after undergoing multiple cycle evaluation, boosting high-efficiency utilization of solar energy.


Association of calprotectin with other inflammatory parameters in the prediction of mortality for ischemic stroke.
Inflammatory response plays an important role in many processes related to acute ischemic stroke (AIS). Calprotectin (S100A8/S100A9), released by monocytes and neutrophils, is a key protein in the regulation of inflammation and thrombosis. The purpose of this study is to evaluate the association of circulating calprotectin with other inflammatory biomarkers and AIS prognosis, as well as the calprotectin content in stroke thrombi. Among the 748 patients treated at a comprehensive stroke center between 2015 and 2017, 413 patients with confirmed acute ischemic injury were prospectively evaluated. Patients with systemic inflammation or infection at onset were excluded. Plasma calprotectin was measured by ELISA in blood samples of AIS patients within the first 24 h. Univariate and multivariate logistic regression models were performed to evaluate its association with mortality and functional independence (FI) at 3 months (defined as modified Rankin Scale < 3) and hemorrhagic transformation (HT) after ischemic stroke. Further, S100A9 was localized by immunostaining in stroke thrombi (n = 44). Higher calprotectin levels were associated with 3-month mortality, HT, and lower 3-month FI. After adjusting for potential confounders, plasma calprotectin remained associated with 3-month mortality [OR (95% CI) 2.31 (1.13-4.73)]. Patients with calprotectin ≥ 2.26 μg/mL were 4 times more likely to die [OR 4.34 (1.95-9.67)]. Addition of calprotectin to clinical variables led to significant improvement in the discrimination capacity of the model [0.91 (0.87-0.95) vs 0.89 (0.85-0.93); p < 0.05]. A multimarker approach demonstrated that patients with increased calprotectin, CRP, and NLR had the poorest outcome with a mortality rate of 42.3% during follow-up. S100A9 protein, as part of the heterodimer calprotectin, was present in all thrombi retrieved from AIS patients. Mean S100A9 content was 3.5% and tended to be higher in patients who died (p = 0.09). Moreover, it positively correlated with platelets (Pearson r 0.46, p < 0.002), leukocytes (0.45, p < 0.01), and neutrophil elastase (0.70, p < 0.001) thrombus content. Plasma calprotectin is an independent predictor of 3-month mortality and provides complementary prognostic information to identify patients with poor outcome after AIS. The presence of S100A9 in stroke thrombi suggests a possible inflammatory mechanism in clot formation, and further studies are needed to determine its influence in resistance to reperfusion.


A fluorescently labeled undecapeptide derived from a protein in royal jelly of the honeybee-royalisin-for specific detection of oxidized low-density lipoprotein.
The probes for detection of oxidized low-density lipoprotein (ox-LDL) in plasma and in atherosclerotic plaques are expected to facilitate the diagnosis, prevention, and treatment of atherosclerosis. Recently, we have reported that a heptapeptide (Lys-Trp-Tyr-Lys-Asp-Gly-Asp, KP6) coupled through the ε-amino group of N-terminal Lys to fluorescein isothiocyanate (FITC), (FITC)KP6, can be useful as a fluorescent probe for specific detection of ox-LDL. In the present study, to develop a novel fluorescent peptide for specific detection of ox-LDL, we investigated the interaction (with ox-LDL) of an undecapeptide corresponding to positions 41 to 51 of a potent antimicrobial protein (royalisin, which consists of 51 residues; from royal jelly of honeybees), conjugated at the N-terminus to FITC in the presence of 6-amino-n-caproic acid (AC) linker, (FITC-AC)-royalisin P11, which contains both sequences, Phe-Lys-Asp and Asp-Lys-Tyr, similar to Tyr-Lys-Asp in (FITC)KP6. The (FITC-AC)-royalisin P11 bound with high specificity to ox-LDL in a dose-dependent manner, through the binding to major lipid components in ox-LDL (lysophosphatidylcholine and oxidized phosphatidylcholine). In contrast, a (FITC-AC)-shuffled royalisin P11 peptide, in which sequences Phe-Lys-Asp and Asp-Lys-Tyr were modified to Lys-Phe-Asp and Asp-Tyr-Lys, respectively, hardly bound to LDL and ox-LDL. These findings strongly suggest that (FITC-AC)-royalisin P11 may be an effective fluorescent probe for specific detection of ox-LDL and that royalisin from the royal jelly of honeybees may play a role in the treatment of atherosclerosis through the specific binding of the region at positions 41 to 51 to ox-LDL.


Dexamethasone antagonism of glucose dyshomeostasis in endotoxin shock.
Dexamethasone acetate (100 microgram IP) protected male Holtzman rats (300-330 gm) against endotoxin shock due to Salmonella enteritidis lipopoly-saccharide B IV. Endotoxin (5.0 mg/rat) produced hypoglycemia within 180 minutes, ie, plasma glucose fell from 87 to 24 mg/dl; dexamethasone prevented the hypoglycemia, ie, plasma glucose levels were 129 mg/dl at 180 minutes after endotoxin. Dexamethasone antagonized both endotoxin-induced depression of hepatic gluconeogenesis and enhanced glucose oxidation as evaluated in vivo. Epididymal fat pads from endotoxic rats (100-110 gm) had increased rates of glucose oxidation as evaluated by the in vitro conversion of 14C-D-glucose to 14CO2. Dexamethasone both in vivo and in vitro antagonized endotoxin glucose hypercatabolism by isolated epididymal fat pads following administrated of endotoxin. Glucocorticoid protection against endotoxin shock is related to antagonism of glucose dyshomeostasis.


LncRNA TUG1 Regulates Cell Viability and Death by Regulating miR-193a-5p/Rab10 Axis in Acute Myeloid Leukemia.
Acute myeloid leukemia (AML) is a serious threat to human health. Long non-coding RNA (lncRNA) Taurine-Upregulated Gene1 (TUG1) has been reported to participate in the development and progression of several cancers, including AML. Herein, we aimed to investigate the pathognomonic role of TUG1 in AML cells and its potential mechanistic pathway. Quantitative real-time PCR (qRT-PCR) assay was applied to detect the expression levels of lncRNA TUG1, miR-193a-5p and Rab10 in AML bone marrow and cell lines. The CCK-8 assay was conducted to assess the cell viability of AML HL-60 and NB4 cells and cell apoptotic assay was performed to assess the cell death. Dual-luciferase reporter assay was carried out to clarify the relationships among TUG1, miR-193a-5p and Rab10. Also, the protein level of Rab10 was examined by Western blot assay. LncRNA TUG1 was up-regulated in AML bone marrow and cells. Functional analysis showed that the silencing of TUG1 suppressed cell viability, while promoted cell death in AML HL-60 and NB4 cells. TUG1 targeted miR-193a-5p and negatively regulated miR-193a-5p expression. Overexpressed miR-193a-5p resulted in the decrease of cell viability and the increase in the cell death in AML cells. Restoration experiments proved that TUG1 regulated the cell viability and death of AML cells through regulating the miR-193a-5p/Rab10 axis. Rab10 was a direct target of miR-193a-5p and was inversely regulated by miR-193a-5p. TUG1 regulated the cell viability and death of AML cells through upregulating Rab10. Silencing of lncRNA TUG1 induces a cytotoxic effect on AML cell lines through sponging miR-193a-5p and the suppression of Rab10.


[Modification of the renotrophic action of adrenal hypercorticism by nutritional factors in uninephrectomized rats].
In the rat renal compensatory hypertrophy (RCH) was enhanced by hyperadrenocorticism induced by the administration of a long acting ACTH at a dose of 18 Y/100 g body weight/d. for 7 d. after uninephrectomy (UN). In the present experiments we compared the differences delta between the weight, the content in protein, RNA and DNA of the left solitary kidney and the same determinations done on the right kidney excised at UN 7 d. earlier. The rats drank freely a isotonic solution of NaCl (G1) or KCl (G2) or glucose (G3, G4). The rats of group G1, G2 and G3 received a standard solid food; the G4 rats ate a K poor diet. About half of the animals were treated with ACTH. RCH occurred in all the rats even when they lost body weight. The gain in weight of the solitary kidney was enhanced in all the rats treated with ACTH but not in the G2 rats loaded with KCl. This renotropic action of hyperadrenocorticism was most prominent in the K depleted G4 rats. The protein/DNA ratio, a marker of cellular hypertrophy, was increased by hyperadrenocorticism in the G1 and D2 rats drinking respectively the NaCl or the KCl solutions. This ratio did not change in the ACTH treated G3 and G4 rats drinking the glucose solution suggesting that, in this experimental condition, cellular hyperplasia and hypertrophy occurred at the same extent. These experiments suggest that, in the uninephrectomized rat, the renotrophic action of ACTH is modulated by nutritional factors. The enhancement of RCH by ACTH may be related to hyperglycemia, hyperinsulinism or altered handling of Na and K by the nephron.


Puerperal infections of the genital tract: a clinical review.
Puerperal genital tract infections, although less common in the 21st century, continue to affect maternal mortality and morbidity rates in the United States. Puerperal genital tract infections include endometritis as well as abdominal and perineal wound infections. These infections interrupt postpartum restoration, increase the potential for readmission to a health care facility, and can interfere with maternal-infant bonding. In addition, unrecognized or improperly treated genital tract infection could extend to other sites via venous circulation or the lymphatic system and increase the risk of severe complications or sepsis. Midwives are leaders in education, low rates of intervention, and prompt recognition of deviation from normal. Because puerperal genital tract infection usually begins after discharge, detailed education for women will encourage preventative health care, prompt recognition, and treatment.