Morphologic characteristics of late stent malapposition after drug-eluting stents implantation by optical coherence tomography follow-up.
Late stent malapposition was frequently observed after DES implantation, which has been associated with the occurrence of late stent thrombosis due to poor neointimal coverage. This study was designed to evaluate the frequency of late stent malapposition at least 1 year after different DESs implantation by optical coherence tomography (OCT). Angiographic and OCT examinations were given to 68 patients who had received total 126 various DESs implantation for at least 1 year to detect late stent malapposition. Malapposed strut distance (MSD), malapposed strut area (MSA), reference lumen area (RLA) and reference stent area (RSA) were checked with off-line OCT analysis. Totally 26 Cypher Select stents, 15 Taxus Liberte stents, 51 Partner stents and 34 Firebird I stents were examined. Among 68 patients who underwent DES implantation, 7 patients (10.3%) had late malapposition. Average RSA, MSA and MSD were (7.9 +/- 2.8) mm(2),(2.0 +/- 1.6) mm(2) and (590 +/- 270) microm respectively. According to the MSA/RSA ratio, 4 patients had slight malapposition, 2 patients had moderate malapposition and 1 patient had severe malapposition. Late stent malapposition is detected frequently after implantation of DES, but if this predisposes to late stent thrombosis and requires any specific therapy needs to be further elucidated.


Social connections and suicidal thoughts and behavior.
Disrupted social connectedness is associated with suicidal thoughts and behaviors among individuals with substance use disorders (SUDs). The current study sought to further characterize this relationship by examining several indices of social connectedness--(a) living alone, (b) perceived social support, (c) interpersonal conflict, and (d) belongingness. Participants (n = 814) were recruited from 4 residential substance-use treatment programs and completed self-report measures of social connectedness as well as whether they had ever thought about or attempted suicide. Multivariate results indicated that interpersonal conflict and belongingness were significant predictors of a history of suicidal ideation, and that belongingness, perceived social support, and living alone were significant predictors of suicide attempt. These results indicate the most consistent support for the relationship between suicidality and thwarted belongingness, and also support the clinical utility of assessing whether individuals live alone.


[Recurrent systemic embolisation in a patient with a large thrombus in left ventricular aneurysm--case report].
A case of a 47-year-old female with the aneurysm of the left ventricle is presented. Several days prior to the hospitalization signs of femoral embolism emerged, which was treated with embolectomy. Echocardiographic examination revealed large thrombus in the cavity of the aneurysm with pedunculated surrounding echo. On the second day after the admission the symptoms of renal artery embolism occurred. Due to recurrent symptoms of peripheral emboli and the lack of a consent for the interventional treatment, fibrinolysis (Actilyse) was applied resulting in the reduction of the thrombus mass in the left ventricle. Subsequent Doppler ultrasound of the renal arteries showed normal flow pattern. During hospitalization general condition has gradually improved and the patient was discharged.


Probe noise characteristics of the spin-exchange relaxation-free (SERF) magnetometer.
In the spin-exchange relaxation-free (SERF) magnetometer, the probe noise is a consequential factor affecting the gradiometric measurement sensitivities. In this paper, we proposed a new characteristics model of the probe noise based on noise separation. Different from noise analysis on single noise source, we considered most of the noise sources influencing the probe system and realized noise sources level measurement experimentally. The results demonstrate that the major noise type changes with the signal frequency. Below 10 Hz, the probe noise mainly comes from the sources independent of light intensity such as the vibration, which accounts for more than 50%; while at 30 Hz, the photon shot noise and the magnetic noise are the main origins, with proportion about 43% and 32%, respectively. Moreover, the results indicate that the optimal probe light intensity with highest sensitivity appears when the response of the magnetic noise is equal to the sum of the electronic noise and half of the shot noise. The optimal intensity gets larger with higher signal frequency. The noise characteristics model could be applied in modulating or differential optical systems and helps sensitivity improvement in SERF magnetometer.


Identifying Species Network Features from Gene Tree Quartets Under the Coalescent Model.
We show that many topological features of level-1 species networks are identifiable from the distribution of the gene tree quartets under the network multi-species coalescent model. In particular, every cycle of size at least 4 and every hybrid node in a cycle of size at least 5 are identifiable. This is a step toward justifying the inference of such networks which was recently implemented by Solís-Lemus and Ané. We show additionally how to compute quartet concordance factors for a network in terms of simpler networks, and explore some circumstances in which cycles of size 3 and hybrid nodes in 4-cycles can be detected.


[Evaluation of selected immunologic indices in children with subglottic laryngitis].
Subglottic laryngitis (croup) is a common disease in children. Its etiology is not quite clear. Thirty children (28 boys and 2 girls), aged between 4 months and up to 5 years (mean 3.6 years), have been hospitalized for the inflammatory swelling of the subglottic space. Laboratory and allergy tests, including: immunoglobulins A, G, M, total IgE, specific IgE blood levels, blood T cell level, and NBT test have been carried out in all children. An increased IgE blood level have been noted in 15 (50%) children, and significantly increased blood level of specific IgE in 10 (33%) children of this subgroup. Blood IgA, IgG, and IgM level have been normal in all children. An increase in NBT test have been seen in 10 (33) children, and a decrease in the number of T cells in 21 (70%) children.


Auditory processing neurons influence song evaluation and strength of mate preference in female songbirds.
Animals use a variety of complex signaling mechanisms to convey an array of information that can be detected by conspecifics and heterospecifics. Receivers of those signals perceive that information and use it to direct their subsequent actions. Thus, communication such as that which occurs between senders and receivers of vocal communication signals can be a powerful model in which to investigate the neural basis of sensory perception and action initiation that underlie decision-making. In this study, we investigated how female songbirds perceive the quality of acoustic signals (songs) performed by males and use that information to express preference for one song among many possible alternatives. We use behavioral measurement of song preference before and after lesion-induced alteration of activity in an auditory processing area (caudal nidopallium, NC) for which we have previously described its interconnections with other auditory areas and downstream reward pathways. Our findings reveal that inactivating NC does not change a female's ability or willingness to perform behavioral indicators of mate choice, nor does it change their ability to identify the songs of individual males. However, lesioning NC does induce a decrease in the strength of song preference for specific males more than others. That decrease does not result in a complete elimination of preference, as female preferences for specific males are still evident but not as strongly expressed after lesioning of NC. Taken together, these data indicate that NC plays a role in a female's strength of preference in song evaluation and mate choice, and activity in NC is an important facet of mate choice.


Fumonisins.
Fusarium moniliforme Sheldon is a common fungal contaminant of corn and produces a variety of mycotoxins. Among these are the recently discovered fumonisins, which are now known to cause certain animal diseases, namely leukoencephalomalacia in horses and pulmonary edema in swine. There is a significant association between their presence in corn and human esophageal cancer in southern Africa. Fumonisin B1 causes liver cancer in rats. Five other fumonisins--B2, B3, B4, A1 and A2, have been isolated; the last two are N-acetates of fumonisins B1 and B2 and do not appear to be toxic. Several other Fusarium species are now known to produce fumonisins. Procedures for detection and determination of fumonisins include thin layer chromatography, liquid chromatography (with fluorescence derivatization), post-hydrolysis gas chromatography, immunochemical assay, and mass spectrometry. In addition to their natural occurrence in corn-based animal feeds and in home-grown African corn used for food, fumonisins are frequently found in commercial corn-based foods. Fumonisins are moderately heat-stable. No effective detoxification process has yet been developed for use with fumonisin-contaminated feeds.


Dosimetric evaluation of two radiotherapy treatment planning systems using report 55 by the AAPM task group 23.
The AAPM Report 55 of Task Group 23 (TG23) is used to verify the accuracy of the calculation algorithm of two radiotherapic treatment planning systems (TPS), which use two pencil beam models (one of the last generation) and a collapsed cone convolution model. The basic feature of TG23 is that it compares dose values computed by TPS and experimental dose measures in situations that reproduce those of simple radiotherapeutic treatments. A threshold of 2% was considered for discrepancies between computed and measured values. The results gave a good accuracy of considered algorithms, except for those points in high dose gradient regions, for which the evaluation as a percentage difference, rather than in millimeters, may overestimate the discrepancies. It was seen that the TG23 package is not only an algorithm verification method, but also a useful instrument for training with dosimetry, configuration and application of a TPS.


Fas/Fas ligand interaction contributes to UV-induced apoptosis in human keratinocytes.
Keratinocytes in human skin undergo apoptosis during various inflammatory processes and after ultraviolet (UV) irradiation. To determine if keratinocyte apoptosis may be mediated by the Fas/APO-1 receptor (CD95), a signal transduction pathway known to initiate programmed cell death of lymphocytes, we investigated Fas expression, modulation, and function in keratinocytes. Keratinocytes constitutively expressed the 2.5- and 1.9-kb Fas transcripts, as well as the 43-kDa Fas protein. Treatment of interferon-gamma-stimulated keratinocytes with Fas agonistic antibody significantly promoted their cell death, indicating that Fas in keratinocytes is functional. UV irradiation induced Fas mRNA expression within 16 to 24 h and Fas protein within 24 h and through 48 h after irradiation. Furthermore, keratinocytes constitutively expressed Fas ligand (FasL) mRNA and protein. UV irradiation induced FasL mRNA as early as 4 h after irradiation and elevated FasL mRNA levels were maintained for at least 24 h postirradiation. Moreover, a FasL neutralizing antibody significantly reduced UV-induced apoptosis of IFN-gamma-treated keratinocytes. Our data strongly suggest that the Fas system contributes to keratinocyte apoptosis in UV-irradiated human skin.


Yield of Abrams needle pleural biopsy in exudative pleural effusion.
Pleural effusion is the abnormal collection of fluid in the pleural space resulting from excessive fluid production or decreased absorption and it is one of the most common clinical conditions that we come across in pulmonology clinics and in hospitals. The objective of prospective study was to evaluate the diagnostic role of Abrams Needle Biopsy in Exudative Pleural Effusion. The study was performed at the Department of Pulmonology, Ayub Teaching Hospital, Abbottabad over a period of 1 year, i.e., January 2008 to December 2008. Sixty-three patients of either sex and all ages with exudative pleural effusion, on whom Abrams Needle Biopsy was performed were included in the study. Minimum of four specimens from each patient were taken and histopathology done. Out of 63 patients, histopathology revealed the cause in 60 (95%) cases. Tuberculosis, malignancy and rheumatoid pleurisy were confirmed in 34, 24, and 2 cases respectively. Specimens of3 patients did not reveal any result and showed non-specific inflammation and were further investigated accordingly. The diagnostic yield of Biopsy was 95%. Pleural biopsy is still a reliable and valuable investigation in diagnosing pleural effusion, provided that adequate pleural specimen is taken.


Hematological, hemorheological, immunological, and morphological studies of spleen autotransplantation in mice: preliminary results.
Using a spleen autotransplantation model, we conducted hematological, hemorheological, immunological, and morphological studies in mice 6 weeks after splenectomy. Sixty male and female A/J inbred mice were equally divided into 3 groups: 1) SE group, splenectomy was performed; 2) AU group, spleen chips were autotransplanted into the omentum without vascular anastomosis following splenectomy; and 3) C group (controls), no intervention in these mice. At postoperative week 6, the following studies were performed: 1) measurement of hematological parameters; 2) hemorheological studies, including relative cell transit time (RCTT) and fibrinogen levels; and 3) activity of peripheral phagocytes, measured by zymozan-induced chemiluminescence, which was calculated in stimulation index values (SI). In addition, histological investigations of autotransplants were conducted. Erythrocyte mean cell volume and platelet counts, RCTT, fibrinogen levels, and activity of phagocytes were significantly higher in the SE group, compared to those in the C group. In the AU group, these parameters were similar to those in the C group. Morphologically, the transplanted spleen showed normal histology. These data indicate that the transplanted spleens restored their function. We conclude that spleen autotransplantation reserves the normal morphology of spleen and restores most of the spleen's hematological, hemorheological, and immunological functions. Both SI index and erythrocyte deformability can be an informative detection of decreasing splenic function. These data suggest that spleen autotransplantation may provide a useful tool to prevent complications following splenectomy in a clinical setting.


Prevalence and correlates of jugular injections among injection drug users.
Jugular injection of drugs has been reported, although little is known about the prevalence of and risk factors associated with this behaviour. We evaluated factors associated with jugular injection among a cohort of injection drug users (IDU) in Vancouver, Canada. We used univariate statistics and logistic regression to examine factors associated with jugular injection among participants in the Vancouver Injecting Drug Users Study (VIDUS), a large prospective cohort study of IDU recruited through snowball sampling methods in Vancouver, Canada. Between December 2004 and November 2005, 780 IDU were followed up as part of VIDUS and 198 (25%) reported jugular injection in the previous 6 months. In multivariate analyses, factors associated independently with jugular injection included: being of the female gender [adjusted odds ratio (aOR) = 1.72, 95% confidence interval (CI): 1.14-2.59; p = 0.010], daily heroin use (aOR = 2.89, 95% CI: 1.93-4.34; p < 0.001), daily cocaine use (aOR = 1.76, 95% CI: 1.12-2.76; p = 0.014], requiring help injecting (aOR = 4.44, 95% CI: 2.64-7.46; p < 0.001), and involvement in the sex-trade (aOR = 2.71, 95% CI: 1.6-4.55; p < 0.001). Reporting a history of jugular injecting was alarmingly high in the cohort and was associated with several identifiable demographic and drug-using characteristics. Given previous reports demonstrating the risk of infection and vascular trauma due to this behaviour, these populations should be considered seriously as a target for safer injecting education.


Variations in physicians' hospitalization practices: a population-based study in Manitoba, Canada.
This paper uses claims data from a universal health care system to describe physicians' hospitalization styles after adjusting for case-mix characteristics of their primary patients. Patients were uniquely assigned to that physician (general or family practitioners, internist, general surgeon, or obstetrician/gynecologist) seen most frequently over each two two-year periods (1972-74 and 1974-76). Four indices were developed including: 1) percentage of primary patients hospitalized; 2) mean number of readmissions for such patients; 3) mean length of stay; and 4) total days of hospitalization per primary care patient (a summary measure combining the first three). Rates of admission, not length of stay, were shown to be strongly related to this summary measure. Marked variations in the hospitalization indices were observed across physicians; these variations cannot be explained by the health or sociodemographic characteristics of a physician's patients. Rural physicians practicing in areas with high bed-to-population ratios and low occupancy rates were particularly high users of hospitals. The economic implications of different practice styles are shown to be large; physicians who were high users of hospitals serve 27 per cent of the patients but their patients consume 42 per cent of the hospital days.


Effect of Obesity on Arithmetic Processing in Preteens With High and Low Math Skills: An Event-Related Potentials Study.
Preadolescence is an important period for the consolidation of certain arithmetic facts, and the development of problem-solving strategies. Obese subjects seem to have poorer academic performance in math than their normal-weight peers, suggesting a negative effect of obesity on math skills in critical developmental periods. To test this hypothesis, event-related potentials (ERPs) were collected during a delayed-verification math task using simple addition and subtraction problems in obese [above 95th body mass index (BMI) percentile] and non-obese (between 5th and 90th BMI percentile) preteens with different levels of math skill; thirty-one with low math skills (14 obese, mean BMI = 26.40, 9.79 years old; 17 non-obese, BMI = 17.45, 9.76 years old) and thirty-one with high math skills (15 obese, BMI = 26.90, 9.60 years old; 16 non-obese, BMI = 17.13, 9.63 years old). No significant differences between weight groups were observed in task accuracy regardless of their mathematical skill level. For ERPs, electrophysiological differences were found only in the subtraction condition; participants with obesity showed an electrophysiologic pattern associated with a reduced ability to allocate attention resources regardless of their math skill level, these differences were characterized by longer P300 latency than their normal-weight peers. Moreover, the participants with obesity with high math skills displayed hypoactivity in left superior parietal lobule compared with their normal-weight peers. Additionally, obese preteens with low math skills displayed smaller arithmetic N400 amplitude than non-obese participants, reflecting difficulties in retrieving visual, semantic, and lexical information about numbers. We conclude that participants with obesity are less able than their normal-weight peers to deploy their attention regardless of their behavioral performance, which seems to have a greater effect on obese participants with low math skills because they also show problems in the retrieval of solutions from working memory, resulting in a delay in the development of mathematical skills.


Development of a Swedish bicycle helmet promotion programme--one decade of experiences.
to describe 10 years of experiences of the Swedish National Bicycle Safety Programme which started during 1990 as part of an initiative taken by the World Health Organization (WHO). In relation to WHO's efforts with regard to accident and injury prevention, a global programme to increase helmet-wearing by two-wheel riders was launched. The idea was to introduce a simple 'vaccine' for everyone that was achievable at a low cost. The Swedish initiative was taken up by the Karolinska Institute and the National Institute of Public Health. at an operational level, all available methods and data sources were utilized in the programme: surveillance of injuries, provision of information and advice, training and supervision, environment and product improvements, and legislation. considerable progress has been made in reducing bicycle-related injuries in Sweden over the last two decades. Cycling injuries among the elderly must be a matter of particular concern. our 10 years of experiences from a bicycle helmet promotion programme lead to the conclusion that there is a case for mandatory helmet wearing, as one of the most important strategies on the national level. But regional and community-based efforts will still need to be more comprehensive. Besides this, efforts must be made to intensify the activities of parties already involved in prevention programmes. New target groups must be approached, such as immigrants, vulnerable social groups, and teenagers. Sustainability of the Swedish Bicycle Helmet Initiative Group, including continued participation of group members and organizations, is the key--in the long term--to protecting Swedish bicyclists against head injuries.


Norovirus diversity in diarrheic children from an African-descendant settlement in Belém, Northern Brazil.
Norovirus (NoV), sapovirus (SaV) and human astrovirus (HAstV) are viral pathogens that are associated with outbreaks and sporadic cases of gastroenteritis. However, little is known about the occurrence of these pathogens in relatively isolated communities, such as the remnants of African-descendant villages ("Quilombola"). The objective of this study was the frequency determination of these viruses in children under 10 years, with and without gastroenteritis, from a "Quilombola" Community, Northern Brazil. A total of 159 stool samples were obtained from April/2008 to July/2010 and tested by an enzyme immunoassay (EIA) and reverse transcription-polymerase chain reaction (RT-PCR) to detect NoV, SaV and HAstV, and further molecular characterization was performed. These viruses were detected only in the diarrheic group. NoV was the most frequent viral agent detected (19.7%-16/81), followed by SaV (2.5%-2/81) and HAstV (1.2%-1/81). Of the 16 NoV-positive samples, 14 were sequenced with primers targeting the B region of the polymerase (ORF1) and the D region of the capsid (ORF2). The results showed a broad genetic diversity of NoV, with 12 strains being classified as GII-4 (5-41.7%), GII-6 (3-25%), GII-7 (2-16.7%), GII-17 (1-8.3%) and GI-2 (1-8.3%), as based on the polymerase region; 12 samples were classified, based on the capsid region, as GII-4 (6-50%, being 3-2006b variant and 3-2010 variant), GII-6 (3-25%), GII-17 (2-16.7%) and GII-20 (1-8.3%). One NoV-strain showed dual genotype specificity, based on the polymerase and capsid region (GII-7/GII-20). This study provides, for the first time, epidemiological and molecular information on the circulation of NoV, SaV and HAstV in African-descendant communities in Northern Brazil and identifies NoV genotypes that were different from those detected previously in studies conducted in the urban area of Belém. It remains to be determined why a broader NoV diversity was observed in such a semi-isolated community.


Exchange nailing of ununited fractures.
Exchange nailing is most appropriate for a nonunion without substantial bone loss. There is no clear consensus regarding the use of exchange nailing in the presence of active, purulent infection. The exchange nail should be at least 1 mm larger in diameter than the nail being removed, and it has been recommended that it be up to 4 mm larger when the nail being removed was greatly undersized. Canal reaming should progress until osseous tissue is observed in the reaming flutes. Exchange nailing is an excellent choice for aseptic nonunions of noncomminuted diaphyseal femoral fractures, with union rates reported to range from 72% to 100%. On the basis of the available literature, exchange nailing cannot be recommended for distal femoral nonunions at this time. Exchange nailing is an excellent choice for aseptic nonunions of noncomminuted diaphyseal tibial fractures, with union rates reported to range from 76% to 96%. On the basis of the available literature, exchange nailing is generally not indicated for humeral nonunions.


Loss of auditory activity modifies the location of potassium channel KCNQ5 in auditory brainstem neurons.
KCNQ5/Kv7.5, a low-threshold noninactivating voltage-gated potassium channel, is preferentially targeted to excitatory endings of auditory neurons in the adult rat brainstem. Endbulds of Held from auditory nerve axons on the bushy cells of the ventral cochlear nucleus (VCN) and calyces of Held around the principal neurons in the medial nucleus of the trapezoid body (MNTB) are rich in KCNQ5 immunoreactivity. We have previously shown that this synaptic distribution occurs at about the time of hearing onset. The current study tests whether this localization in excitatory endings depends on the peripheral activity carried by the auditory nerve. Auditory nerve activity was abolished by cochlear removal or intracochlear injection of tetrodotoxin (TTX). Presence of KCNQ5 was analyzed by immunocytochemistry, Western blotting, and quantitative reverse transcription polymerase chain reaction. After cochlear removal, KCNQ5 immunoreactivity was virtually undetectable at its usual location in endbulbs and calyces of Held in the anteroventral CN and in the MNTB, respectively, although it was found in cell bodies in the VCN. The results were comparable after intracochlear TTX injection, which drastically reduced KCNQ5 immunostaining in MNTB calyces and increased immunolabeling in VCN cell bodies. Endbulbs of Held in the VCN also showed diminished KCNQ5 labeling after intracochlear TTX injection. These results show that peripheral activity from auditory nerve afferents is necessary to maintain the subcellular distribution of KCNQ5 in synaptic endings of the auditory brainstem. This may contribute to adaptations in the excitability and neurotransmitter release properties of these presynaptic endings under altered input conditions.


Cardiovascular effects of the essential oil of Aniba canelilla bark in normotensive rats.
Cardiovascular effects of intravenous (i.v.) treatment with the essential oil of the bark of Aniba canelilla (EOAC) were investigated in normotensive rats. In both pentobarbital-anesthetized and conscious rats, i.v. bolus injections of EOAC (1 to 20 mg/kg) elicited similar and dose-dependent hypotension and bradycardia. Pretreatment of anesthetized rats with bilateral vagotomy significantly reduced the bradycardia without affecting the hypotension. In conscious rats, pretreatment with hexamethonium (30 mg/kg, i.v.) significantly reduced the EOAC-induced bradycardia without affecting the hypotension. The opposite effect was observed after i.v. pretreatment with the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl esther (L-NAME, 20 mg/kg). However, both EOAC-induced hypotension and bradycardia were significantly reduced by pretreatment with methylatropine (1 mg/kg, i.v.). In rat endothelium-containing aorta preparations, EOAC (1-600 microg/mL) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction [IC50 (geometric mean+/-95% confidence interval)=64.5 (45.6-91.2) microg/mL)], an effect that was significantly reduced by the addition of atropine (10 microM) in the perfusion medium [IC50=109.5 (72.5-165.4) microg/mL)]. Furthermore, the vasorelaxant effects of the EOAC were also but significantly reduced [IC50=139.1 (105.2-183.9) microg/mL)] by removal of the vascular endothelium. Furthermore, the CaCl2-induced contractions in calcium-free medium were reduced and even fully abolished by EOAC (100 and 600 microg/mL), respectively. However, EOAC (600 microg/mL) was without significant effect on caffeine-induced contractions in calcium-free medium. These data show that i.v. treatment of rats with EOAC induces dose-dependent hypotension and bradycardia, which occurred independently. The bradycardia appears mainly dependent upon the presence of an operational and functional parasympathetic drive to the heart. However, the hypotension is due to an active vascular relaxation rather than withdrawal of sympathetic tone. This relaxation seems partly mediated by an endothelial L-arginine/nitric oxide pathway through peripheral muscarinic receptor activation (endothelium-dependent relaxation) and predominantly through an inhibition of calcium inward current (endothelium-independent relaxation).


Impact Evaluation of a System-Wide Chronic Disease Management Program on Health Service Utilisation: A Propensity-Matched Cohort Study.
The New South Wales Health (NSW Health) Chronic Disease Management Program (CDMP) delivers interventions to adults at risk of hospitalisation for five target chronic conditions that respond well to ambulatory care: diabetes, hypertension, chronic obstructive pulmonary disease, congestive heart failure, and coronary artery disease. The intervention consists of two main components: (1) care coordination across sectors (acute, ambulatory, and community care from both public and private sectors) and clinical specialties, facilitated by program care coordinators, and (2) health coaching including management of lifestyle risk factors and medications and self-management. These components were broadly prescribed by the head office of NSW Health, which funded the program, and were implemented by regional health services (local health districts) in ways that best suited their own history, environment, workforce, and patient need. We used a propensity-matched cohort study to evaluate health service utilisation after enrolment in the CDMP. The evaluation cohort included 41,303 CDMP participants enrolled between 1 January 2011 and 31 December 2013 who experienced at least one hospital admission or emergency department (ED) presentation for a target condition in the 12 mo preceding enrolment. Potential controls were selected from patients not enrolled in the CDMP but experiencing at least one hospital admission or ED presentation over the same period. Each CDMP patient in the evaluation cohort was matched to one control using 1:1 propensity score matching. The primary outcome was avoidable hospitalisations. Secondary outcomes included avoidable readmissions, avoidable bed days, unplanned hospitalisations, unplanned readmissions, unplanned bed days, ED presentations, and all-cause death. The primary analysis consisted of 30,057 CDMP participants and 30,057 matched controls with a median follow-up of 15 mo. Of those, 25,638 (85.3%) and 25,597 (85.2%) were alive by the end of follow-up in the CDMP and control groups, respectively. Baseline characteristics (including history of health service utilisation) were well balanced between the matched groups. In both groups, utilisation peaked just before the time of enrolment/matching, declined sharply immediately following enrolment, and then continued to decrease more gradually; however, after enrolment, avoidable and unplanned health service utilisation remained higher for CDMP participants compared to controls. The adjusted yearly rate of avoidable hospital admissions was 0.57 (95% CI 0.52 to 0.62) in the CDMP group versus 0.33 (95% CI 0.31 to 0.37) in the control group (adjusted rate ratio 1.70, 95% CI 1.62 to 1.79, p < 0.001). Significant increases in service utilisation were also observed for unplanned hospitalisations (1.42, 95% CI 1.37 to 1.47, p < 0.001) and ED presentations (1.37, 95% CI 1.32 to 1.42, p < 0.001) as well as avoidable (2.00, 95% CI 1.80 to 2.22, p < 0.001) and unplanned (1.51, 95% CI 1.40 to 1.62, p < 0.001) readmissions and avoidable (1.70, 95% CI 1.59 to 1.82, p < 0.001) and unplanned (1.43, 95% CI 1.36 to 1.49, p < 0.001) bed days. No evidence of a difference was seen for all-cause death (adjusted risk ratio 0.96, 95% CI 0.96 to 1.01, p = 0.10) or non-avoidable hospitalisations (all hospitalisations minus avoidable hospitalisations; adjusted rate ratio 1.03, 95% CI 0.97 to 1.10, p = 0.26). Despite the robustness of these results to sensitivity analyses, in the absence of a randomised control group, one cannot exclude the possibility of residual or unmeasured confounding that was not controlled for by the matching process and multivariable analyses. Participation in the CDMP was associated with an increase in avoidable hospital admissions compared to matched controls but no difference in the rate of other types of hospitalisation or death. A possible explanation is that the program identified conditions that required participants to be hospitalised. Service utilisation decreased sharply following its peak for both groups. This finding reflects the natural tendency for high-risk patients to show reductions in use following intense phases of service utilisation and highlights that, despite the additional complexity, a carefully selected control group is essential when assessing the effectiveness of interventions on hospital use.


Life weariness and suicidal thoughts in late life: a national study in Sweden.
This study aimed at investigating the point prevalence of life weariness and suicidal thoughts and their relationship with socio-demographic characteristics in a population of older adults in Sweden. Data from 7913 individuals aged 60 years and older were drawn from the Swedish National Study on Aging and Care, a collaborative study in Sweden. Life weariness and suicidal thoughts were measured by one item derived from the Montgomery-Åsberg Depression Rating Scale. A multinomial regression model was used to investigate the relationships of socio-demographic characteristics with life weariness and suicidal thoughts. Living in urban and semi-urban areas, being of advanced age, being divorced and having lower educational levels were related to life weariness. Living in a residential care facility, being widowed or unmarried, being born in a non-Nordic European country and experiencing financial difficulties were related to both life weariness and suicidal thoughts. Sex was found to be unrelated to either life weariness or suicidal thoughts. This study found that several socio-demographic variables were associated with life weariness and suicidal thoughts among older adults. Specific attention to older individuals with these characteristics may be warranted as they might be more vulnerable to life weariness and suicidal thoughts.


Characterization of the rheological, textural, and sensory properties of samples of commercial US cream cheese with different fat contents.
In this study, 18 commercial samples of cream cheeses from the United States, including full-fat, Neufchatel or one-third less fat, and fat-free cheeses were analyzed for their rheological, textural, and sensory properties. Dynamic rheological properties were measured by small-amplitude oscillatory rheology during heating from 5 to 80 degrees C and cooling from 80 to 5 degrees C. The parameters measured were storage modulus (G') and loss tangent (LT). Hardness of cream cheeses was determined by penetration and spreadability tests with a texture analyzer. Quantitative descriptive sensory analysis was performed by a trained panel to determine textural properties including firmness, stickiness, cohesiveness of mass, gumminess, difficulty to dissolve, particle size, and difficulty to spread. Principal component analysis of sensory and instrumental parameters was performed to identify relationships between these different parameters and to group samples with similar characteristics. A standard recipe for preparation of cheesecakes was used to test the influence of type of cream cheese on cake properties. Hardness of cheesecakes was also determined by penetration. Most full-fat cream cheeses showed significantly greater G' values than the Neufchatel or fat-free cheeses at temperatures below 25 degrees C during the heating cycle. For the cheeses containing fat (full fat and Neufchatel), G' values steeply decreased during heating up to 40 degrees C; the decrease was greater for full-fat cream cheese compared with Neufchatel cheeses. In full-fat cream cheese, one maximum in the LT profile was observed during heating at temperatures below 40 degrees C. In Neufchatel cheeses, a smaller maximum in LT was observed at temperatures below 40 degrees C, whereas fat-free cream cheeses showed no noticeable maximum LT in this temperature region. Most full-fat cream cheeses had greater values of hardness as determined by penetration or spreadability compared with Neufchatel or fat-free cheeses. Sensory analysis indicated that full-fat cream cheeses were firmer, more cohesive, more difficult to dissolve and spread, and less sticky than Neufchatel or fat-free cheeses. The high hardness of full-fat cream cheese is presumably due to its greater fat content because after homogenization of the cream cheese mix, fat globules are partly covered with casein and participate in the aggregation of casein particles, reinforcing the structure of this product. These results indicate that there are significant differences in the textural properties of cream cheese made with different fat contents.


Adjunctive protein synthesis inhibitor antibiotics for toxin suppression in Staphylococcus aureus infections: a systematic appraisal.
Protein synthesis inhibitor antibiotics inhibit synthesis of new proteins, including exotoxins and other important virulence determinants in Staphylococcus aureus. A summary of the literature regarding the use of adjunctive protein synthesis inhibitors for toxin suppression in the setting of S. aureus infections is presented.


Home-based exercise therapy in patients awaiting liver transplantation: protocol for an observational feasibility trial.
Liver disease is the third most common cause of premature mortality in the UK. Liver failure accelerates frailty, resulting in skeletal muscle atrophy, functional decline and an associated risk of liver transplant waiting list mortality. However, there is limited research investigating the impact of exercise on patient outcomes pre and post liver transplantation. The waitlist period for patients listed for liver transplantation provides a unique opportunity to provide and assess interventions such as prehabilitation. This study is a phase I observational study evaluating the feasibility of conducting a randomised control trial (RCT) investigating the use of a home-based exercise programme (HBEP) in the management of patients awaiting liver transplantation. Twenty eligible patients will be randomly selected from the Queen Elizabeth University Hospital Birmingham liver transplant waiting list. Participants will be provided with an individually tailored 12-week HBEP, including step targets and resistance exercises. Activity trackers and patient diaries will be provided to support data collection. For the initial 6 weeks, telephone support will be given to discuss compliance with the study intervention, achievement of weekly targets, and to address any queries or concerns regarding the intervention. During weeks 6-12, participants will continue the intervention without telephone support to evaluate longer term adherence to the study intervention. On completing the intervention, all participants will be invited to engage in a focus group to discuss their experiences and the feasibility of an RCT. The protocol is approved by the National Research Ethics Service Committee North West - Greater Manchester East and Health Research Authority (REC reference: 17/NW/0120). Recruitment into the study started in April 2017 and ended in July 2017. Follow-up of participants is ongoing and due to finish by the end of 2017. The findings of this study will be disseminated through peer-reviewed publications and international presentations. In addition, the protocol will be placed on the British Liver Trust website for public access. NCT02949505; Pre-results.


Prognostic value of HIV-1 Gag-specific CD4+ T-cell responses for progression to AIDS analyzed in a prospective cohort study.
The causal relationship between HIV-specific CD4+ T-cell responses and viral control and the effect of these responses on the natural history of HIV infection is unclear. In a detailed longitudinal study, functional HIV-1 Gag-specific CD4+ T cells were analyzed in long-term asymptomatic individuals (LTA; n = 6) and progressors to AIDS (n = 7) with a median follow-up of, respectively, 118 and 57 months. Next, HIV-specific CD4+ T-helper cell responses were measured in a prospective cohort study among 96 HIV seroconverters and were related to clinical endpoints using Cox proportional hazard analyses. In the detailed study, no difference for HIV-specific helper-cell responses between LTAs and progressors was observed early in infection, but Gag-specific CD4+ T cells producing IL-2 or IFNgamma were lost in progressors late in infection. Multivariate proportional hazard analyses in the prospective cohort study showed that HIV-specific IL-2+, IFNgamma+, or IL-2+IFNgamma+ CD4+ T cells early after seroconversion had no prognostic value for the rate of progression to AIDS. Our results are compatible with viral load determining the nature and magnitude of HIV-specific CD4+ T-cell responses, rather than HIV-specific CD4+ T-cell responses controlling HIV plasma viral load.


Participation of pigment epithelium in ocular immune privilege. 3. Epithelia cultured from iris, ciliary body, and retina suppress T-cell activation by partially non-overlapping mechanisms.
The ocular microenvironment is immunosuppressive and anti-inflammatory. Since various ocular pigmented epithelia contribute to this microenvironment, we studied the relative capacities of pigment epithelial (PE) cells cultured from the iris, ciliary body, and retina of mouse eyes to suppress T-cell activation in vitro. Pigment epithelium was cultured from iris, ciliary body, and retina for 14 days, then assayed for the capacity, directly or across transwell membranes, to suppress mixed lymphocyte reactions and anti-CD3 stimulation of T cells. Potential molecules responsible for suppression were examined by attempting to block suppression with appropriate reagents, and by using mice with pertinent mutant or disrupted genes. We found that PE cells from all three ocular tissue sources profoundly suppressed T-cell activation in vitro. While iris PE suppressed poorly when separated from T cells by a transwell membrane (implying that cell contact is necessary), retina PE suppressed fully even in the presence of such a membrane (implying that soluble factors were responsible). Ciliary body PE used both soluble factors as well as cell contact to achieve suppression. Suppression could not be ascribed to TGFbeta, IFNgamma, TNFalpha, CD48, or ICAM-1, or to interactions between CD40 and CD154, or CD95 and CD95 ligand. Galectin-1, a galactoside-binding protein, was found to be expressed on all cultured PE cells, but only retinal pigment epithelium (RPE) from galectin-1 KO mice showed reduced capacity to inhibit T-cell activation. Cultured pigment epithelia from iris, ciliary body, and retina comparably suppress T-cell activation in vitro, but by partially different mechanisms. Although RPE cells suppress in part through expression of galectin-1, the molecular mediators of suppression by iris and ciliary body PE remain to be identified.


ACE I/D polymorphism is associated with mortality in a cohort study of patients starting with dialysis.
In dialysis patients, only a few follow-up studies have addressed the relationship between the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene and mortality, but the available data are contradictory. A cohort of 453 consecutive patients starting dialysis between January 1999 and January 2002 and participating in a Dutch multicenter prospective study was examined. Patients who died within 3 months after the start of dialysis were excluded. Patients were followed until date of death or censoring in November 2003. The ACE II, ID, and DD genotype frequencies were 24.3% (N = 110), 50.1% (N = 227), and 25.6% (N = 116). Besides a slightly higher number of Caucasians in the DD group, all other patient characteristics of the 3 ACE groups were similar at the start of dialysis. After adjustment for age, comorbidity, and ethnic background, patients with the ID and DD genotype showed an increased hazard ratio (HR) for all-cause mortality of 1.55 (95% CI 1.00-2.42) and 2.30 (95% CI 1.41-3.75), compared to patients with the II genotype. Slightly lower HRs were found for cardiovascular mortality. All groups of primary kidney disease showed a 2- to 3-fold increased adjusted HR for DD. The DD genotype identifies dialysis patients at an increased risk for mortality.


Blood banking for hematopoietic stem cell transplantation.
The number of umbilical cord cell transplants is increasing worldwide. The results are comparable to allogeneic bone marrow transplantation in a large variety of hematological diseases that are curable by bone marrow transplantation and, so far, the incidence of graft-versus-host disease has been limited. The advantages of using cord blood are related to the high number of hematopoietic progenitors present in the circulation at birth and to the relative immune immaturity of the newborn. A project is described to establish a European cord blood bank in order to obtain related or unrelated, matched or mismatched hematopoietic stem cells for transplantation to patients without a bone marrow donor.


Mechanisms of blood pressure oscillation caused by central nervous system ischemic response.
The experimental results on the hemodynamics and mechanisms of the systemic arterial pressure oscillation (SAPO) produced by the side pressure exertion procedure (SPEP) are presented. The SAPO has revealed us the existence of reciprocal structure at the base of the nervous integration of the cardiovascular system. The reciprocity is found between the type I and type II vasomotor neurons in the bulbar cardiovascular center. The latter is in charge of making the hierarchical set-up in the cardiovascular system, in which blood is supplied to the brain and the cardiac muscle at the expense of blood supply to the other organs. The former is in charge of building antihierarchical set-up, in which blood is provided to the other organs including the cardiac muscle at the sacrifice of blood supply to the brain. During the SAPO, the two groups of the reticular vasomotor neurons alternately discharge, and the two set-ups appear by turns in the cardiovascular system. Thus the animal can survive the SPEP for hours. The SAPO is caused by the coupling of the existing reciprocity with a newly generated central oscillator. The central oscillator has a segmental structure. It is composed of unit oscillators combined in series. This structure works as a ruler of the powerful CNS ischemic response and endows the SAPO with both rigidity and plasticity. It has shown the existence of segmental organization in the CNS in the chronological aspect also and the role of the CNS as that more than mere reflex centers. The study on the SAPO has opened a way to the physiology on emergence of a new order in the animal body.


A pilot study showing differences in glycosylation patterns of IgG subclasses induced by pneumococcal, meningococcal, and two types of influenza vaccines.
The presence of a carbohydrate moiety on asparagine 297 in the Fc part of an IgG molecule is essential for its effector functions and thus influences its vaccine protective effect. Detailed structural carbohydrate analysis of vaccine induced IgGs is therefore of interest as this knowledge can prove valuable in vaccine research and design and when optimizing vaccine schedules. In order to better understand and exploit the protective potential of IgG antibodies, we carried out a pilot study; collecting serum or plasma from volunteers receiving different vaccines and determining the IgG subclass glycosylation patterns against specific vaccine antigens at different time points using LC-ESI-MS analysis. The four vaccines included a pneumococcal capsule polysaccharide vaccine, a meningococcal outer membrane vesicle vaccine, a seasonal influenza vaccine, and a pandemic influenza vaccine. The number of volunteers was limited, but the results following immunization indicated that the IgG subclass which dominated the response showed increased galactose and the level of sialic acid increased with time for most vaccinees. Fucose levels increased for some vaccinees but in general stayed relatively unaltered. The total background IgG glycosylation analyzed in parallel varied little with time and hence the changes seen were likely to be caused by vaccination. The presence of an adjuvant in the pandemic influenza vaccine seemed to produce simpler and less varied glycoforms compared to the adjuvant-free seasonal influenza vaccine. This pilot study demonstrates that detailed IgG glycosylation pattern analysis might be a necessary step in addition to biological testing for optimizing vaccine development and strategies.


Norepinephrine and calcium responses to altered sodium intake in modulating and non-modulating high-renin hypertension.
Sodium sensitivity in subjects with high-renin hypertension has been associated with non-modulation of cardiovascular and biochemical responses to alteration in sodium intake. Using the percentage suppression of plasma renin activity in response to an increase in dietary sodium intake, high-renin hypertensive subjects were categorized in two groups. In association with the increase in sodium intake, modulators showed greater than 58% suppression of plasma renin activity, and significant reductions in mean arterial pressure, plasma aldosterone, norepinephrine and serum calcium concentration. Non-modulators had no significant change in plasma renin activity, mean arterial blood pressure, plasma aldosterone, norepinephrine or serum calcium concentration. The blood pressure response to an increase in dietary sodium intake may be a composite of responses of the renin-angiotensin-aldosterone axis, the adrenergic nervous system and calcium regulatory system.


In vitro studies on controlled-release cellulose acetate films for local delivery of chlorhexidine, indomethacin, and meloxicam.
Delivery of medications into periodontal pockets to suppress or eradicate the pathogenic microbiota or modulate the inflammatory response, thereby limiting periodontal tissue destruction, has attracted significant interest with the purpose of effective periodontal treatment. However, no study has previously attempted to develop a controlled-release formulation of anti-inflammatory agents to be used in the field of periodontology. The aim of the present study was to examine the in vitro release profile of chlorhexidine gluconate, indomethacin, and meloxicam from cellulose acetate films. Cellulose acetate films containing chlorhexidine gluconate, indomethacin, and meloxicam were prepared and cut in a form to fit to the periodontal pocket anatomy. The release of active agents was studied in 10 ml artificial saliva at 37 degrees C. Apparatus Vibrax was used at 150 r.p.m. Determinations were carried out spectrophotometrically and the release profiles were plotted as a function of time. The formulations showed two different release patterns for a total observation period of approximately 120 h. When the formulations of the three active agents were compared, the release patterns of meloxicam and chlorhexidine gluconate were found to be similar, while the indomethacin-containing formulation exhibited the fastest release rate. As a conclusion, cellulose acetate may be a suitable inert material for obtaining a prolonged local release of various anti-inflammatory agents like meloxicam. Further in vitro and in vivo studies are required before starting clinical applications of these controlled-release formulations of anti-inflammatory agents.


On the nucleation and initial film growth of rod-like organic molecules.
In this article, some fundamental topics related to the initial steps of organic film growth are reviewed. General conclusions will be drawn based on experimental results obtained for the film formation of oligophenylene and pentacene molecules on gold and mica substrates. Thin films were prepared via physical vapor deposition under ultrahigh-vacuum conditions and characterized in-situ mainly by thermal desorption spectroscopy, and ex-situ by X-ray diffraction and atomic force microscopy. In this short review article the following topics will be discussed: What are the necessary conditions to form island-like films which are either composed of flat-lying or of standing molecules? Does a wetting layer exist below and in between the islands? What is the reason behind the occasionally observed bimodal island size distribution? Can one describe the nucleation process with the diffusion-limited aggregation model? Do the impinging molecules directly adsorb on the surface or rather via a hot-precursor state? Finally, it will be described how the critical island size can be determined by an independent measurement of the deposition rate dependence of the island density and the capture-zone distribution via a universal relationship.


Application of 3D-QSAR in the rational design of receptor ligands and enzyme inhibitors.
Quantitative structure-activity relationships (QSARs) are frequently employed in medicinal chemistry projects, both to rationalize structure-activity relationships (SAR) for known series of compounds and to help in the design of innovative structures endowed with desired pharmacological actions. As a difference from the so-called structure-based drug design tools, they do not require the knowledge of the biological target structure, but are based on the comparison of drug structural features, thus being defined ligand-based drug design tools. In the 3D-QSAR approach, structural descriptors are calculated from molecular models of the ligands, as interaction fields within a three-dimensional (3D) lattice of points surrounding the ligand structure. These descriptors are collected in a large X matrix, which is submitted to multivariate analysis to look for correlations with biological activity. Like for other QSARs, the reliability and usefulness of the correlation models depends on the validity of the assumptions and on the quality of the data. A careful selection of compounds and pharmacological data can improve the application of 3D-QSAR analysis in drug design. Some examples of the application of CoMFA and CoMSIA approaches to the SAR study and design of receptor or enzyme ligands is described, pointing the attention to the fields of melatonin receptor ligands and FAAH inhibitors.


Essential role of DNA-PKcs and plasminogen for the development of doxorubicin-induced glomerular injury in mice.
Susceptibility to doxorubicin-induced nephropathy (DIN), a toxic model for the induction of proteinuria in mice, is related to the single-nucleotide polymorphism (SNP) C6418T of the Prkdc gene encoding for the DNA-repair enzyme DNA-PKcs. In addition, plasminogen (Plg) has been reported to play a role in glomerular damage. Here, we investigated the interdependence of both factors for the development of DIN. Genotyping confirmed the SNP of the Prkdc gene in C57BL/6 (PrkdcC6418/C6418) and 129S1/SvImJ (PrkdcT6418/T6418) mice. Intercross of heterozygous 129SB6F1 mice led to 129SB6F2 hybrids with Mendelian inheritance of the SNP. After doxorubicin injection, only homozygous F2 mice with PrkdcT6418/T6418 developed proteinuria. Genetic deficiency of Plg (Plg-/-) in otherwise susceptible 129S1/SvImJ mice led to resistance to DIN. Immunohistochemistry revealed glomerular binding of Plg in Plg+/+ mice after doxorubicin injection involving histone H2B as Plg receptor. In doxorubicin-resistant C57BL/6 mice, Plg binding was absent. In conclusion, susceptibility to DIN in 129S1/SvImJ mice is determined by a hierarchical two-hit process requiring the C6418T SNP in the Prkdc gene and subsequent glomerular binding of Plg. This article has an associated First Person interview with the first author of the paper.


Extra-esophageal manifestations of GERD: who responds to GERD therapy?
Gastroesophageal reflux disease (GERD) is a common disease that is defined as a condition that develops when the reflux of stomach contents causes troublesome symptoms. In addition to the esophageal manifestations of heartburn and regurgitation, the role of GERD in causing extra-esophageal symptoms, such as laryngitis, asthma, cough, chest pain, and dental erosions, is increasingly recognized with renewed interest. Due to the poor sensitivity of endoscopy and pH monitoring, and the poor specificity of laryngoscopy, empiric therapy with proton pump inhibitors (PPI) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. In those who are unresponsive to such therapy, other diagnostic testing such as impedance/pH monitoring may be reasonable in order to exclude continued acid or weakly acid reflux. Recent data suggest that patients with extra-esophageal symptoms who have concomitant typical symptoms, moderate-sized hiatal hernia and moderate reflux on pH testing may respond better to acid suppressive therapy. This group only accounts for 20-30 % of patients commonly referred for suspected GERD. PPI-unresponsive patients usually have causes other than GERD for their extra-esophageal signs and symptoms and continued PPI therapy in this group is not recommended.


Practical approaches to minimize problems with missing quality of life data.
Missing information on quality of life (QOL) is a significant problem in many cancer trials particularly for patients with advanced disease, where clinical deterioration may be a reason for not responding to quality of life assessments. Examples from four clinical trials are presented where non-respondents to quality of life assessments have poorer health than respondents. In this context, auxiliary outcome variables, such as health status, may be useful proxies in assessing the impact of missing QOL data on estimated treatment effects. This approach is illustrated in a trial of palliative treatment in advanced cancer. A method for imputation of missing QOL data based on auxiliary outcome variables is also illustrated. However, the most effective method of minimizing the problem of missing data is in designing the trial with preventative strategies in place. Since some missing data due to deteriorating health may still occur, the design should include the collection of auxiliary QOL information. Preventative strategies are illustrated with an ongoing trial in advanced breast cancer.


miR-30a radiosensitizes non-small cell lung cancer by targeting ATF1 that is involved in the phosphorylation of ATM.
Increasing number of studies report that microRNAs play important roles in radiosensitization. miR-30a has been proved to perform many functions in the development and treatment of cancer, and it is downregulated in non-small cell lung cancer (NSCLC) tissues and cells. This study was conducted to understand if miR-30a plays a role in the radiosensitivity of NSCLC cells. Radiosensitivity was examed by colony survival assay and tumor volume changing in vitro and in vivo, respectively. Bioinformatic analysis and luciferase reporter assays were used to distinguish the candidate target of miR-30a. qRT-PCR and western blotting were carried out to detect the relative expression of mRNAs and proteins. Cell cycle and cell apoptosis were determined by flow cytometry. Our results illustrated miR-30a could increase the radiosensitivity of NSCLC, especially in A549 cell line. In vivo experiment also showed the potential radiosensitizing possibility of miR-30a. Further exploration validated that miR-30a was directly targ-eting activating transcription factor 1 (ATF1). In studying the ataxia-telangiectasia mutated (ATM) associated effects on cell radiosensitivity, we found that miR-30a could reduce radiation induced G2/M cell cycle arrest and may also affect radiation induced apoptosis. Together, our results demonstrated that miR-30a may modulate the radiosensitivity of NSCLC through reducing the function of ATF1 in phosphorylation of ATM and have potential therapeutic value.


Distinct roles of the RasGAP family proteins in C. elegans associative learning and memory.
The Ras GTPase activating proteins (RasGAPs) are regulators of the conserved Ras/MAPK pathway. Various roles of some of the RasGAPs in learning and memory have been reported in different model systems, yet, there is no comprehensive study to characterize all gap genes in any organism. Here, using reverse genetics and neurobehavioural tests, we studied the role of all known genes of the rasgap family in C. elegans in associative learning and memory. We demonstrated that their proteins are implicated in different parts of the learning and memory processes. We show that gap-1 contribute redundantly with gap-3 to the chemosensation of volatile compounds, gap-1 plays a major role in associative learning, while gap-2 and gap-3 are predominantly required for short- and long-term associative memory. Our results also suggest that the C. elegans Ras orthologue let-60 is involved in multiple processes during learning and memory. Thus, we show that the different classes of RasGAP proteins are all involved in cognitive function and their complex interplay ensures the proper formation and storage of novel information in C. elegans.


Changes in Smoking Status and Behaviors After the First 10 Months of COVID-19 Pandemic in Indonesia.
There remains inconclusive evidence on potential changes in smoking status and behaviors during the coronavirus disease 2019 (COVID-9) pandemic, especially in developing countries. This study explores the direction of changes in smoking status and behaviors after 10 months of the COVID-19 pandemic in Indonesia as well as examining the association between economic shocks and changes in smoking behaviors. Primary data were gathered through a phone survey targeting productive-age mobile-phone users in Indonesia (n = 1082). Descriptive analysis was employed to determine changes in smoking status and behaviors 10 months into the pandemic, while logistic regression analysis was used to investigate how employment shocks, financial strain, COVID-19-related indicators, and demographic characteristics were associated with smoking behaviors of people who continue smoking. Respondents experiencing changes in smoking status were dominated by people who persistently smoked during the pandemic, while those who quit, relapsed, and started smoking, was extremely small. Nevertheless, a considerable portion of people who continue smoking adjusted their smoking behaviors: 40.3% reduced smoking intensity and 25.3% switched to lower-price cigarettes. Multivariable regression analysis revealed that, among people who continue smoking, those who experienced financial strain during the pandemic had higher odds of reducing smoking intensity, while those who switched to lower job status had higher odds of switching to cheaper cigarettes. The research has shown that smoking status and behaviors of people who continue smoking mostly remained unchanged after 10 months of the COVID-19 pandemic. Changes in employment and financial conditions during the pandemic were associated with modified smoking behaviors. This study is the first to determine the direction and analyze the factors of changes in smoking during the COVID-19 pandemic in Indonesia. This new understanding should help improve predicting the trends in smoking in future crises or pandemics in developing countries, specifically Indonesia. The discovered patterns on smokers' reaction to an exogenous shock may provide evidence to support tobacco control policies in Indonesia.


Extracellular cadmium in the bronchoalveolar space of long-term tobacco smokers with and without COPD and its association with inflammation.
Tobacco contains cadmium, and this metal has been attributed a causative role in pulmonary emphysema among smokers, although extracellular cadmium has not to date been quantified in the bronchoalveolar space of tobacco smokers with or without COPD. We determined whether cadmium is enhanced in the bronchoalveolar space of long-term tobacco smokers with or without COPD in vivo, its association with inflammation, and its effect on chemokine release in macrophage-like cells in vitro. Bronchoalveolar lavage (BAL), sputum, and blood samples were collected from current, long-term smokers with and without COPD and from healthy nonsmokers. Cadmium concentrations were determined in cell-free BAL fluid using inductively coupled plasma mass spectrometry. Blood monocyte-derived macrophages were exposed to cadmium chloride in vitro. Depending upon the type of sample, molecular markers of inflammation were quantified either as protein (enzyme-linked immunosorbent assay) or as mRNA (real-time polymerase chain reaction). Cadmium concentrations were markedly increased in cell-free BAL fluid of smokers compared to that of nonsmokers (n=19-29; P<0.001), irrespective of COPD. In these smokers, the measured cadmium displayed positive correlations with macrophage TNF-α mRNA in BAL, neutrophil and CD8(+) cell concentrations in blood, and finally with IL-6, IL-8, and MMP-9 protein in sputum (n=10-20; P<0.05). The cadmium chloride exposure caused a concentration-dependent increase in extracellular IL-8 protein in monocyte-derived macrophages in vitro. In conclusion, extracellular cadmium is enhanced in the bronchoalveolar space of long-term smokers and displays pro-inflammatory features. Its pathogenic role in tobacco-induced disease deserves further evaluation.


Detection and characterization of a B cell stimulatory factor (BSF-TC) derived from a bone marrow stromal cell line.
Stromal cell lines derived from murine bone marrow support the growth of immature pre-B cells and produce cytokines that affect the growth and differentiation of other hematopoietic precursors. Conditioned medium (CM) from one such line (TC-1) stimulated marked proliferation of B cells previously activated by anti-Ig (anti-Ig blasts). Proliferation of anti-Ig blasts was not induced by purified cytokines known to be produced by TC-1 (CSF-1, GM-CSF, or G-CSF) or by IL-1, IL-2, IL-3, IL-4, IL-5, or IL-6. Furthermore, IL-2, IL-4, and IL-5, alone or in combination, failed to support proliferation or differentiation of anti-Ig blasts. TC-1 CM enhanced proliferation of B cells that were co-cultured with LPS, anti-Ig, or dextran sulfate; co-stimulation with anti-Ig was unaffected by the presence of monoclonal anti-IL-4. Proliferation of low, but not high, density B cells isolated from spleen was directly stimulated by TC-1 CM. These results suggest that bone marrow stromal cells produce a novel B cell stimulatory factor (BSF-TC) that induces proliferation of activated B cells.


AM and PM measurement of gastric potential difference and prostacyclin production in humans: effects of ranitidine.
It has been previously documented that aspirin induced gastric injury of healthy male volunteers was greater in the morning than in the evening. We have also reported that fasting gastric acid secretion rates and gastric retention times for solids were lower in the morning hours of the circadian cycle. We hypothesized, therefore, that defensive factors in the human stomach may exhibit circadian rhythmicity with greater vulnerability to noxious agents during the morning hours. It has also been hypothesized that an antisecretory agent, with reported protective effects, such as Ranitidine, would affect gastric defense mechanisms differently at different times in the circadian cycle. Transmural electrical potential difference (PD) and prostacyclin (PGI2) production by mucosal biopsy specimens were chosen as putative indicators of gastric defensive status. Accordingly, morning (1000) and evening (2200) studies were performed on 10 fasting healthy male subjects with and without oral Ranitidine (150 mg) given 3 hr before oro-gastric intubation for the measurement of PD and the removal of mucosal biopsy samples.(ABSTRACT TRUNCATED AT 250 WORDS)


Contact depigmentation caused by an azo dye in alta.
Alta, a scarlet-red solution used by some Indian women as a cosmetic to colour their feet, was found to be associated with depigmentation at the site of application. Chromatographic and spectroscopic analysis of 3 brands of alta confirmed the presence of 2 dyes: Crocein Scarlet MOO (CSM) (brilliant crocein) and rhodamine B (tetraethyl rhodamine). Patch testing produced depigmentation at the site of application of alta, CSM and para-phenylenediamine (PPD). Although PPD has been reported to produce leukoderma, azo dyes have not previously been reported as depigmenting agents.


Curriculum Development of a Health Informatics Master Course in Understanding Technology.
Education in health informatics is an important contribution to the digital transformation in health care services, and there is a need to combine health and technology competencies. Traditional ways with separation of health sciences and computer science have shortcomings, and there is need for individuals with a holistic view and relevant education background for improving the technology-supported clinical work processes. This paper presents how the curriculum was organised in a course in "Understanding Technology", which was a part of a Master's Programme in Health Informatics. The course targeted different aspects of technology for students with a diverse background, and it was organised with the aim to provide the students with theoretical technical insights and apply the knowledge through problem-solving and practical use. The course was decentralised and had a student-centred teaching approach over one semester.


Renal Epithelial Cell Injury Induced by Calcium Oxalate Monohydrate Depends on their Structural Features: Size, Surface, and Crystalline Structure.
Urinary crystals in normal and kidney stone patients often differ in crystal sizes and surface structures, but the effects of different crystal properties on renal tubular epithelial cells remain unclear. This study aimed to compare the cytotoxicity of micron/nano-calcium oxalate monohydrate (COM) crystals with sizes of 50 nm, 200 nm, 1 μm, 3 μm, and 10 μm to African green monkey renal epithelial (Vero) cells, to reveal the effect of crystal size and surface structure on cell injury, and to investigate the pathological mechanism of calcium oxalate kidney stones. Cell viability, cellular biochemical parameters, and internalized crystal amount in Vero cells were closely associated with the size of COM crystals. At the same concentration (200 μg/mL), COM-1 μm induced the most serious injury to Vero cells and caused the most significant change to cellular biochemical parameters, which were related to the specific porous structure and highest internalized amount in Vero cells. By contrast, COM-50 nm and COM-200 nm crystals lost their small size effect because of serious aggregation and weakened their toxicity to cells. COM-3 μm and COM-10 μm crystals were too large for cells to completely internalize; these crystals also exhibited a low specific surface area and thus weakened their toxicity. The excessive expression of intracellular ROS and reduction of the free-radical scavenger SOD were the main reasons for cell injury and eventually caused necrotic cell death. Crystal size, surface structure, aggregation, and internalization amount were closely related to the cytotoxicity of COM crystals.


Bimodal dialysis: theoretical and computational investigations of adequacy indices for combined use of peritoneal dialysis and hemodialysis.
A theoretically correct method for evaluating the adequacy of bimodal dialysis (BMD), a combination of peritoneal dialysis (PD) and hemodialysis (HD) in the same patient, is lacking. We therefore performed computer simulations using a variable-volume, two-compartment urea kinetic model for 1-week treatments with 1) HD with three sessions, HD3, 2) continuous ambulatory PD, CAPD, 3) 6 days of CAPD and 1 day with HD session, and 4) 5 days of CAPD and 2 days with HD. Four dialysis adequacy indices (KT/V, stdKT/V, fractional solute removal, FSR, and equivalent clearance, EKR) were analyzed using four different reference methods for normalization of urea amount and concentration: 1) peak value, 2) peak average value, 3) time average value, and 4) treatment time average value. The analyses show that a proposed simplified rule of adding one third of weekly FSR for HD3 for each dialysis session and one seventh of weekly FSR for CAPD for each PD day for prediction of weekly FSR for BMD provides a fair prediction, although some corrections may be necessary, depending on the chosen reference method. In particular, KT/V may be added using this rule. We conclude that theoretically correct adequacy indices for BMD may be defined and calculated by using numerical simulations.


Contribution of Bacillus Isolates to the Flavor Profiles of Vanilla Beans Assessed through Aroma Analysis and Chemometrics.
Colonizing Bacillus in vanilla (Vanilla planifolia Andrews) beans is involved in glucovanillin hydrolysis and vanillin formation during conventional curing. The flavor profiles of vanilla beans under Bacillus-assisted curing were analyzed through gas chromatography-mass spectrometry, electronic nose, and quantitative sensory analysis. The flavor profiles were analytically compared among the vanilla beans under Bacillus-assisted curing, conventional curing, and non-microorganism-assisted curing. Vanilla beans added with Bacillus vanillea XY18 and Bacillus subtilis XY20 contained higher vanillin (3.58%±0.05% and 3.48%±0.10%, respectively) than vanilla beans that underwent non-microorganism-assisted curing and conventional curing (3.09%±0.14% and 3.21%±0.15%, respectively). Forty-two volatiles were identified from endogenous vanilla metabolism. Five other compounds were identified from exogenous Bacillus metabolism. Electronic nose data confirmed that vanilla flavors produced through the different curing processes were easily distinguished. Quantitative sensory analysis confirmed that Bacillus-assisted curing increased vanillin production without generating any unpleasant sensory attribute. Partial least squares regression further provided a correlation model of different measurements. Overall, we comparatively analyzed the flavor profiles of vanilla beans under Bacillus-assisted curing, indirectly demonstrated the mechanism of vanilla flavor formation by microbes.


Full Length Interleukin 33 Aggravates Radiation-Induced Skin Reaction.
The interleukin (IL)-1 family member IL-33 has been described as intracellular alarmin with broad roles in wound healing, skin inflammation but also autoimmunity. Its dichotomy between full length (fl) IL-33 and the mature (m) form of IL-33 and its release by necrosis is still not fully understood. Here, we compare functional consequences of both forms in the skin in vivo, and therefore generated two lines of transgenic mice which selectively overexpress mmIL-33 and flmIL-33 in basal keratinocytes. Transgene mRNA was expressed at high level in skin of both lines but not in organs due to the specific K14 promoter. We could demonstrate that transgenic overexpression of mmIL-33 in murine keratinocytes leads to a spontaneous skin inflammation as opposed to flmIL-33. K14-mmIL-33 mice synthesize and secrete high amounts of mmIL-33 along with massive cutaneous manifestations, like increased epidermis and dermis thickness, infiltration of mast cells in the epidermis and dermis layers and marked hyperkeratosis. Using skin inflammation models such as IL-23 administration, imiquimod treatment, or mechanical irritation did not lead to exacerbated inflammation in the K14-flmIL-33 strain. As radiation induces a strong dermatitis due to apoptosis and necrosis, we determined the effect of fractionated radiation (12 Gy, 4 times). In comparison to wild-type mice, an increase in ear thickness in flmIL-33 transgenic mice was observed 25 days after irradiation. Macroscopic examination showed more severe skin symptoms in irradiated ears compared to controls. In summary, secreted mmIL-33 itself has a potent capacity in skin inflammation whereas fl IL-33 is limited due to its intracellular retention. During tissue damage, fl IL-33 exacerbated radiation-induced skin reaction.


Clinical approaches to skin cleansing of the diaper area: practice and challenges.
Cleansing and care of the diaper area require special consideration to maintain barrier function of the skin in this area and repair the barrier when it is compromised. Diaper dermatitis occurs commonly; understanding and modification of predisposing factors are imperative for caregivers. In this paper, we review important factors in diaper area care, including skin pH, the local microbiome, irritant and allergic potential of contactants, and application of topical agents.


Controlling the atomic distribution in PtPd nanoparticles: thermal stability and reactivity during NO abatement.
In situ X-ray absorption spectroscopy and mass spectrometry measurements were employed to simultaneously probe the atom specific short range order and reactivity of Pd and PtPd nanoparticles towards NO decomposition at 300 °C. The nanoparticles were synthesized by a well controlled, eco-friendly wet chemical reduction of metal salts and later supported on activated carbon. Particularly for the bimetallic PtPd samples, distinct atomic arrangements were achieved using a seeding growth method, which allowed producing a random nanoalloy, or nanoparticles with Pt- or Pd-rich core. X-ray photoelectron spectroscopy, transmission electron microscopy, and X-ray diffraction provided additional insights on their electronic, morphological and long range order structural properties. The results revealed that the higher the thermal induced atomic migration observed within the nanoparticles during thermal treatments, the least were their reactivity for NO abatement.


Randomized feasibility trial of a digital intervention for hypertension self-management.
Home blood pressure monitoring (HBPM) can improve hypertension management. Digital tools to facilitate routinized HBPM and patient self-care are underutilized and lack evidence of effectiveness. MyBP provides video-based education and automated text messaging to support continuous BP self-monitoring with recurring feedback. In this pragmatic trial, we sought to generate preliminary evidence of feasibility and efficacy in community-dwelling adults ≥55 y/o with hypertension recruited from primary care offices. Enrollees were provided a standard automatic BP cuff and randomized 2:1 to MyBP vs treatment-as-usual (control). Engagement with MyBP was defined as the proportion of BP reading prompts for which a reading was submitted, tracked over successive 2-week monitoring periods. Preliminary measures of efficacy included BP readings from phone-supervised home measurements and a self-efficacy questionnaire. Sixty-two participants (40 women, 33 Blacks, mean age 66, mean office BP 164/91) were randomized to MyBP (n = 41) or a control group (n = 21). Median follow-up was 22.9 (SD = 6.7) weeks. In the MyBP group, median engagement with HBPM was 82.7% (Q1 = 52.5, Q3 = 89.6) and sustained over time. The decline in systolic [12 mm Hg (SD = 17)] and diastolic BP [5 mm Hg (SD = 7)] did not differ between the two treatment groups. However, participants with higher baseline systolic BP assigned to MyBP had a greater decline compared to controls [interaction effect estimate -0.56 (-0.96, -0.17)]. Overall hypertension self-efficacy improved in the MyBP group. In conclusion, trial results show that older hypertensive adults with substantial minority representation had sustained engagement with this digital self-monitoring program and may benefit clinically.


Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia.
Preeclampsia is a major cause of maternal, fetal, and neonatal mortality worldwide. Although the etiology of preeclampsia is still unclear, recent studies suggest that its major phenotypes, high blood pressure and proteinuria, are due in part to excess circulating soluble fms-like tyrosine kinase-1 concentrations. Soluble fms-like tyrosine kinase-1 is an endogenous antiangiogenic protein that is made by the placenta and acts by neutralizing the proangiogenic proteins vascular endothelial growth factor and placental growth factor. High serum soluble fms-like tyrosine kinase-1 and low serum free placental growth factor and free vascular endothelial growth factor have been observed in preeclampsia. Abnormalities in these circulating angiogenic proteins are not only present during clinical preeclampsia but also antedate clinical symptoms by several weeks. Therefore, this raises the possibility of measuring circulating angiogenic proteins in the blood and the urine as a diagnostic and screening tool for preeclampsia. The availability of a test to predict preeclampsia would be a powerful tool in preventing preeclampsia-induced mortality, especially in developing nations, where high-risk specialists are limited. This review will summarize our current understanding of the role of circulating angiogenic proteins in the pathogenesis and clinical diagnosis/prediction of preeclampsia.


[HEALTH SCARES: A CHRONICLE UNNECESSARY ANXIETY].
A health scare is an event characterized by fear of catastrophic consequences with little actual results. Regardless of these negligible results, the health, social and economic impacts of such events may be significant. Health scares are spread throughout four major groups: the media, relevant medical experts, policy makers and the public at large. In this review, we described two recent cases in Israel: the case of Eltroxin exchange that occurred in Israel as well as other countries, in addition to the polio virus spread in sewage, in the context of health scares. Furthermore, we summarized the interaction between these groups, focusing on their functioning in selected health scares from the previous two decades. There is increased need for creating a priori coordinating methods, in order to deal efficiently with such events in the future. In that way, the implications of health scares can be reduce to minimum.


Cohesin dynamic association to chromatin and interfacing with replication forks in genome integrity maintenance.
Proliferating cells need to accurately duplicate and pass their genetic material on to daughter cells. Problems during replication and partition challenge the structural and numerical integrity of chromosomes. Diverse mechanisms, as the DNA replication checkpoint, survey the correct progression of replication and couple it with other cell cycle events to preserve genome integrity. The structural maintenance of chromosomes (SMC) cohesin complex primarily contributes to chromosome duplication by mediating the tethering of newly replicated sister chromatids, thus assisting their equal segregation in mitosis. In addition, cohesin exerts important functions in genome organization, gene expression and DNA repair. These are determined by cohesin's ability to bring together different DNA segments and, hence, by the fashion and dynamics of its interaction with chromatin. It recently emerged that cohesin contributes to the protection of stalled replication forks through a mechanism requiring its timely mobilization from unreplicated DNA and relocation to nascent strands. This mechanism relies on DNA replication checkpoint-dependent cohesin ubiquitylation and promotes nascent sister chromatid entrapment, likely contributing to preserve stalled replisome-fork architectural integrity. Here we review how cohesin dynamic association to chromatin is controlled through post-translational modifications to dictate its functions during chromosome duplication. We also discuss recent insights on the mechanism that mediates interfacing of replisome components with chromatin-bound cohesin and its contribution to the establishment of sister chromatid cohesion and the protection of stalled replication forks.


Beta-blockers: friend or foe in asthma?
Recently, β-blockers have been suggested as a potential maintenance treatment option for asthma. The aim of this review is to provide an overview of the current knowledge of the potential benefits and risks of β-blocker therapy for asthma. Systematic literature review. No significant increase in the number of patients requiring rescue oral corticosteroid for an exacerbation of asthma has been observed after initiation of β-blocker treatment. Patients with mild to moderate reactive airway disease, probably both asthma and chronic obstructive pulmonary disease, may have a limited fall in forced expiratory volume in 1 second (FEV1) following single-dose administration of β-blocker, whereas no change in FEV1 has been reported following long-term administration. In a murine model of asthma, long-term administration of β-blockers resulted in a decrease in airway hyperresponsiveness, suggesting an anti-inflammatory effect. In keeping with this, long-term administration of a nonselective β-blocker to steroid-naïve asthma patients has shown a dose-dependent improvement in airway hyperresponsiveness, and either an asymptomatic fall in FEV1 or no significant change in FEV1. Furthermore, available studies show that bronchoconstriction induced by inhaled methacholine is reversed by salbutamol in patients on regular therapy with a β-blocker. On the other hand, a recent placebo-controlled trial of propranolol and tiotropium bromide added to inhaled corticosteroids revealed no effect on airway hyperresponsiveness and a small, not statistically significant, fall in FEV1 in patients classified as having mild to moderate asthma. The available, although limited, evidence suggests that a dose-escalating model of β-blocker therapy to patients with asthma is well tolerated, does not induce acute bronchoconstriction, and, not least, may have beneficial effects on airway inflammation and airway hyperresponsiveness in some patients with asthma. Further studies addressing the potential role of β-blocker therapy for asthma are clearly needed, but careful selection of the target population is warranted.


Measurement of articular cartilage surface irregularity in rat knee contracture.
To design novel quantitative methods to evaluate the irregularity of articular cartilage surface; and to apply these methods for assessment of surface irregularity in a rat knee contracture model. A total of 117 rat knees were either immobilized or sham-operated and harvested after 2, 4, 8, 16, or 32 weeks, and 11 knees were not operated. Standardized histologic sections were digitized and the contours of femoral and tibial cartilage surfaces were delineated. The rates of change in cartilage contour were calculated. Rate of change above a defined threshold constituted surface irregularity. In non-operated knees, cartilage surface irregularity in femur and tibia amounted to 3.1 +/- 0.5%. Immobilized knees showed significantly more irregularities than the sham-operated knees at all time points (2 weeks: 5.3 +/- 0.6% vs 3.1 +/- 0.4%; 4 weeks: 10.5 +/- 0.9% vs 4.4 +/- 0.9%; 8 weeks: 12.0 +/- 1.8% vs 4.9 +/- 0.2%; 16 weeks: 13.7 +/- 2.0% vs 4.9 +/- 0.4%; and 32 weeks: 13.8 +/- 1.4% vs 3.4 +/- 0.6%; all p < 0.05). No difference was observed between sham-operated and non-operated knees. Increasing duration of immobilization in weeks (t) significantly correlated with more surface irregularity, described by the logarithmic formula: % irregularity = 6.6 + 2.1 ln (t), (F = 59.3, p < 0.001). This formula showed that irregularity progressed rapidly after immobilization and plateaued after 8 weeks. We designed methods to quantify cartilage surface irregularity and applied them to a contracture model. Cartilage surface irregularities appeared after 2 weeks of immobilization and progressed rapidly to plateau after 8 weeks. Combined with microscopic magnetic resonance imaging, this measurement of cartilage surface irregularity may constitute a sensitive tool to detect cartilage degeneration clinically.


Subarachnoid hemorrhage grading scales: a systematic review.
Numerous systems are reported for grading the clinical condition of patients following subarachnoid hemorrhage (SAH). The literature was reviewed for articles pertaining to the grading of such patients, including publications on the Hunt and Hess Scale, Fisher Scale, Glasgow Coma Score (GCS), and World Federation of Neurological Surgeons Scale. This article reviews the advantages and limitations of these scales as well as more recent proposals for other grading systems based on these scales with or without addition of other factors known to be prognostic for outcome after SAH. There remain substantial deficits in the literature regarding grading of patients with SAH. Most grading scales were derived retrospectively, and the intra- and interobserver variability has seldom been assessed. Inclusion of additional factors increases the complexity of the scale, possibly making it less likely to be adopted for routine usage and increasing (only marginally in some cases) the ability to predict prognosis. Until further data are available, it is recommended that publications on patients with SAH report at least the admission GCS as well as factors commonly known to influence prognosis, such as age, pre-existing hypertension, the amount of blood present on admission computed tomography, time of admission after SAH, aneurysm location and size, presence of intracerebral or intraventricular hemorrhage, and blood pressure at admission.


Distinct mechanisms of modulation of angiotensin II type I receptor gene expression in heart and aorta.
The purpose of the present study was to test the hypothesis that hypertension induced by reduced renal mass (RRM) upregulates gene expression of the type 1 angiotensin II (Ang II) receptor (AT1) in the thoracic aorta and heart through an Ang II-dependent mechanism. Three groups of rats were given 1% NaCl water and subjected to RRM, RRM plus captopril (RRM+Cap, 30 mg/kg per day), or sham surgery. Tail-cuff systolic blood pressure was significantly elevated in RRM and RRM+Cap rats compared with sham-operated rats. The ratios of the medial wall area of the thoracic aorta and heart weight to body weight were significantly elevated in RRM and RRM+Cap rats compared with sham-operated rats. Northern blot analysis indicated that the ratio of AT1 to GAPDH mRNA in the aorta was significantly higher in RRM (1.85 +/- 0.52) compared with sham-operated (0.21 +/- 0.04) and RRM+Cap (0.55 +/- 0.20) rats. In contrast, the ratio of AT1 to GAPDH mRNA in the heart was significantly increased in both RRM (1.09 +/- 0.23) and RRM+Cap (1.00 +/- 0.09) compared with sham-operated (0.34 +/- 0.06) rats. Thus, RRM hypertension upregulates AT1 mRNA expression in both the hypertrophied aorta and heart. Captopril treatment without altering blood pressure in RRM rats prevents the increase in AT1 mRNA in the aorta but not the heart. These results suggest that different tissue-specific mechanisms of AT1 gene regulation exist; ie, in aorta, an Ang II-or kinin-dependent mechanism is operant, whereas in heart, RRM-induced upregulation of AT1 mRNA may be pressure dependent.


Reliable Output Feedback Control for T-S Fuzzy Systems With Decentralized Event Triggering Communication and Actuator Failures.
Due to the unavailability of full state variables in many control systems, this paper is concerned with the design of reliable observer-based output feedback controller for a class of network-based Takagi-Sugeno fuzzy systems with actuator failures. In order to better allocate network resources under the case that the sensor nodes are physically distributed, the decentralized event triggering communication scheme is adopted such that each sensor node is capable to determine the transmission of its local measurement information independently. Considering that the implementation of the controller may not be synchronized with the plant trajectories due to asynchronous premise variables with such communication mechanism, a novel piecewise fuzzy observer-based output feedback controller is developed. By applying a piecewise Lyapunov function and some techniques on matrix convexification, an approach to the design of observer and controller gain is derived for the augmented closed-loop system to be asymptotically stable with a guaranteed H∞ performance and reduced transmission frequency. Finally, two examples are given to show the effectiveness of the developed method.


Prevalence of ascariasis and ancylostomiasis in families: a collaborative inquiry.
A collaborative survey was carried out to estimate the prevalence of ascariasis and ancylostomiasis in random samples of 200 families in each of 3 different communities: a city slum (CS), an industrial township (IT), a farming village community (FVC). Stool examination was done by Kato's qualitative thick smear method. Ascariasis was prevalent in all the three communities; the percentage of families with multiple members infected varied from 50 to 91 per cent; the percentage of members infected within such a family varied from 48 to 74 per cent; the infection was highly prevalent (41-78%) in all age groups excepts adults in the IT. From 8 to 11 per cent of persons with ascariasis were negative on stool examination but passed worms after medication. Ancylostomiasis was arevelent mainly in the FVC and to a less extent in the IT; the percentage of families with multiple members infected was 83 per cent in the FVC and 17 per cent in the IT; the percentage of members infected within such a family was 54 per cent in the FVC and 58 per cent in the IT. All the persons surveyed received a single 10 mg/kg dose of pyrantel pamoate (Combantrin*, Pfizer) which was well tolerated.


Geographic, seasonal, and precipitation chemistry influence on the abundance and activity of biological ice nucleators in rain and snow.
Biological ice nucleators (IN) function as catalysts for freezing at relatively warm temperatures (warmer than -10 degrees C). We examined the concentration (per volume of liquid) and nature of IN in precipitation collected from Montana and Louisiana, the Alps and Pyrenees (France), Ross Island (Antarctica), and Yukon (Canada). The temperature of detectable ice-nucleating activity for more than half of the samples was > or = -5 degrees C based on immersion freezing testing. Digestion of the samples with lysozyme (i.e., to hydrolyze bacterial cell walls) led to reductions in the frequency of freezing (0-100%); heat treatment greatly reduced (95% average) or completely eliminated ice nucleation at the measured conditions in every sample. These behaviors were consistent with the activity being bacterial and/or proteinaceous in origin. Statistical analysis revealed seasonal similarities between warm-temperature ice-nucleating activities in snow samples collected over 7 months in Montana. Multiple regression was used to construct models with biogeochemical data [major ions, total organic carbon (TOC), particle, and cell concentration] that were accurate in predicting the concentration of microbial cells and biological IN in precipitation based on the concentration of TOC, Ca(2+), and NH(4)(+), or TOC, cells, Ca(2+), NH(4)(+), K(+), PO(4)(3-), SO(4)(2-), Cl(-), and HCO(3)(-). Our results indicate that biological IN are ubiquitous in precipitation and that for some geographic locations the activity and concentration of these particles is related to the season and precipitation chemistry. Thus, our research suggests that biological IN are widespread in the atmosphere and may affect meteorological processes that lead to precipitation.


Irradiation-induced grain growth and defect evolution in nanocrystalline zirconia with doped grain boundaries.
Grain boundaries are effective sinks for radiation-induced defects, ultimately impacting the radiation tolerance of nanocrystalline materials (dense materials with nanosized grains) against net defect accumulation. However, irradiation-induced grain growth leads to grain boundary area decrease, shortening potential benefits of nanostructures. A possible approach to mitigate this is the introduction of dopants to target a decrease in grain boundary mobility or a reduction in grain boundary energy to eliminate driving forces for grain growth (using similar strategies as to control thermal growth). Here we tested this concept in nanocrystalline zirconia doped with lanthanum. Although the dopant is observed to segregate to the grain boundaries, causing grain boundary energy decrease and promoting dragging forces for thermally activated boundary movement, irradiation induced grain growth could not be avoided under heavy ion irradiation, suggesting a different growth mechanism as compared to thermal growth. Furthermore, it is apparent that reducing the grain boundary energy reduced the effectiveness of the grain boundary as sinks, and the number of defects in the doped material is higher than in undoped (La-free) YSZ.


Development of a novel monolith-bioreactor for the treatment of VOC-polluted air.
A novel bioreactor packed with ceramic monolith colonized by a toluene-degrading culture was investigated in order to assess its suitability for waste gas treatment. Operational parameters that were considered included start-up of the bioreactor, toluene loading rate, changes in gas flow rate, liquid feed mode, and steady-state operation. This is the first report on the treatment of toluene-polluted air in such a biological monolith reactor. Data on performance and stability have been obtained showing that this system is suitable for waste gas treatment. Removal efficiencies around 90% could be maintained at different gas flow rates, although this value gradually dropped when increasing the load above 30 g m(-3) h(-1). Interestingly, omitting the continuous feed of a liquid trickling phase improved the reactor's performance. One potential drawback that needs to be minimized is related to clogging after long term operation. Further studies aimed at optimizing this novel application would allow reaching a high performance under long-term, stable conditions.