Plasma fibrinogen and incident hypertension in the Atherosclerosis Risk in Communities (ARIC) Study.
Several cross-sectional studies have reported a positive association between plasma fibrinogen levels and prevalent hypertension. Other studies have reported a positive association between hypertension and whole-blood or plasma viscosity, to which fibrinogen contributes. To our knowledge, there has been no prospective study of fibrinogen and incident hypertension. We measured plasma fibrinogen levels in a population-based cohort study of middle-aged adults and related it to the occurrence of incident hypertension (systolic blood pressure > or = 140 mmHg or diastolic blood pressure > or = 90 mmHg or use of antihypertensive medication) over 6 years. There was a moderately strong positive association between fibrinogen levels and prevalent hypertension in both men and women, with the odds of hypertension elevated by 50% for the highest fibrinogen quartile versus the lowest. Among 7884 participants at risk, 1609 developed hypertension over 6 years. Adjusted for age, race, field center and baseline systolic blood pressure, the odds ratio of incident hypertension in relation to fibrinogen quartiles was 1.0, 1.07, 1.21 and 1.43 in men (P= 0.003 for trend) and 1.0, 0.92, 0.99 and 0.99 in women (P= 0.89 for trend). After adjustment for other risk factors, the odds ratios were 1.0, 1.03, 1.15 and 1.29 (P= 0.045 for trend) in men and remained nonsignificant in women. Despite a moderately strong positive association between fibrinogen levels and prevalent hypertension in both sexes, there was only a weak positive association between fibrinogen levels and incident hypertension in men and no association in women. Whether an elevated fibrinogen level is a risk factor for, or a consequence of, hypertension remains unclear.


Regional, demographic and national influences on attitudes and beliefs with regard to physical activity, body weight and health in a nationally representative sample in the European Union.
Although the benefits of physical activity regarding body-weight gain and health in general are now widely accepted, physical activity levels remain low among citizens in the western world. This could be attributed to certain attitudes and beliefs about physical activity. Identifying and understanding these parameters would be the first step in an attempt to increase the levels of physical activity in populations generally characterized as having a sedentary lifestyle. The aim of the present study was to identify the attitudes and beliefs regarding physical activity, body weight and health in a nationally representative sample in the EU and in particular to explore the demographic and national (cultural) influences on attitudes towards physical activity. In each member state of the EU, approximately 1000 adults aged 15 years and over, were selected to complete an interviewer-assisted face-to-face questionnaire. Overall, a sample of 15,239 individuals in the EU participated in the study. Subject selection was quota-controlled to ensure samples in each country were nationally representative. On a European level wide variations were observed regarding the levels, beliefs and attitudes towards physical activity. More positive beliefs were observed among Finns, while less positive beliefs were observed among southern Europeans. A similar pattern was observed for attitudes, with the Portuguese having the highest percentage feeling that they do not need to be more physically active than they already are. However, most southern Europeans felt that a campaign would encourage them to become more active than they already are. On a demographic level, the youngest, more educated and most physically active subjects had more positive attitudes and beliefs towards physical activity and the health benefits derived from it; while for the overweight, beliefs and attitudes toward physical activity were related primarily to the benefits related to weight control. Lower levels of physical activity, an unwillingness to become active among non-participants and confusion regarding the weight gain benefits and general health benefits of exercise were reported more frequently among southern Europeans and older and less educated subjects. The Finns scored highest in all these parameters, possibly due to the programmes implemented and the beliefs and behaviour changes observed in this country during the last few years. The actions taken in Finland and their benefits could be employed appropriately in the other European states.


Evaluation of two frailty indices, with practical application in a vaccine clinical trial.
Frail older adults are at increased risk of poor clinical outcomes. Frailty assessment is therefore important in clinical trials to understand the benefits and harms of interventions. However, consensus is lacking on how frailty should be assessed.We developed a prospectively specified index using a battery of formal tests and instruments and a retrospectively generated index using medical comorbidities and patient reported outcomes (PROs) within an adjuvanted recombinant zoster vaccine (RZV) trial (NCT02979639). For both frailty indices (FIs), a total deficit score was calculated as the accumulation of deficits and participants were categorized as non-frail, pre-frail and frail. We assessed (1) the feasibility and validity of both FIs; (2) the impact of RZV vaccine reactogenicity by frailty status on Short Form-36 [SF-36] physical functioning (PF) scores.Of 401 participants, aged ≥50 years, 236 (58.9%) were categorized non-frail, 143 (35.7%), pre-frail, and 22 (5.5%) frail using the prospective FI. Corresponding numbers for the retrospective FI were 192 (47.9%), 169 (42.1%) and 40 (10.0%), respectively. Strong concordance was observed between the frailty status assessments (P < .001). The proportion defined as frail increased from 1.5%, to 10.4% in participants aged 50-59, and ≥70 years, respectively, for the prospective FI. Corresponding numbers for the retrospective FI were 3.7%, and 17.2%, respectively. RZV vaccination was associated with a transient, non-clinically meaningful, decrease on the SF-36 PF score in frail participants.Both frailty indices provided similar results. The retrospectively generated FI offers the advantage of being easier to incorporate into vaccine clinical trials of older adults.


Thermally Triggered Injectable Underwater Adhesives.
A novel bioinspired underwater adhesive based on the injectable aqueous solution of a graft copolymer with a thermoresponsive backbone is reported, which turns into a sticky hydrogel just below body temperature. With this topology, the collapse of the backbones upon the thermal transition leads to the formation of a percolating network of strong hydrophobic domains. Similar to pressure-sensitive adhesives (PSAs), the hydrogel goes through fibrillation and extensive energy dissipation in large deformations, giving it an edge over conventional chemical hydrogels, which are typically elastic and inherently nonsticky. This capability comes from the hydrophobic nanoscaffold, which resists large deformations to minimize its contact with water. Since hydrophobic interactions are not weakened in water, the behavior of the hydrogel is maintained in aqueous medium. Chemistry-insensitive adhesion of this hydrogel offers a major advantage over current injectable adhesives, which rely on in situ chemical crosslinking reactions with tissues.


Clinico-bacteriological profile of primary pyodermas in Kashmir: a hospital-based study.
Pyodermas are a common group of infectious dermatological conditions on which few studies have been conducted. This study aimed to characterise the clinical and bacteriological profile of pyodermas, and to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infection in primary pyodermas in a dermatology outpatient department in Kashmir. Methods We conducted a hospital based cross-sectional study in the outpatient Department of Dermatology, Sexually Transmitted Diseases and Leprosy of Shri Maharaja Hari Singh Hospital, Srinagar, Jammu and Kashmir, India. Patients presenting with primary pyodermas were included in the study. A detailed history and complete physical and cutaneous examination was carried out along with microbiological testing to find aetiological microorganisms and their respectiveantimicrobial susceptibility patterns. Antimicrobial susceptibility testing, including that for methicillin resistance, was carried out by standard methods as outlined in the current Clinical and Laboratory Standards Institute guidelines. Results In total, 110 patients were included; the age of the study population ranged from 3 to 65 years (mean age 28 years); 62% were male. Poor personal hygiene was noted in 76 (69%). Furunculosis (56; 51%) was the most common clinical presentation. Staphylococcus aureus was isolated in 89 (81%) of cases, and MRSA formed 54/89 (61%) of Staphylococcus aureus isolates. All MRSA strains were sensitive to vancomycin. Conclusion The prevalence of MRSA was high in this sample of communityacquired primary pyodermas. It is therefore important to monitor the changing trends in bacterial infection and their antimicrobial susceptibility patterns and to formulate a definite antibiotic policy which may be helpful in decreasing the incidence of MRSA infection.


Cooperators benefit through reputation-based partner choice in economic games.
Explaining unconditional cooperation, such as donations to charities or contributions to public goods, continues to present a problem. One possibility is that cooperation can pay through developing a reputation that makes one more likely to be chosen for a profitable cooperative partnership, a process termed competitive altruism (CA) or reputation-based partner choice. Here, we show, to our knowledge, for the first time, that investing in a cooperative reputation can bring net benefits through access to more cooperative partners. Participants played a public goods game (PGG) followed by an opportunity to select a partner for a second cooperative game. We found that those who gave more in the PGG were more often selected as desired partners and received more in the paired cooperative game. Reputational competition was even stronger when it was possible for participants to receive a higher payoff from partner choice. The benefits of being selected by a more cooperative partner outweighed the costs of cooperation in the reputation building phase. CA therefore provides an alternative to indirect reciprocity as an explanation for reputation-building behaviour. Furthermore, while indirect reciprocity depends upon individuals giving preference to those of good standing, CA can explain unconditional cooperation.


Physical weight loading induces expression of tryptophan hydroxylase 2 in the brain stem.
Sustaining brain serotonin is essential in mental health. Physical activities can attenuate mental problems by enhancing serotonin signaling. However, such activity is not always possible in disabled individuals or patients with dementia. Knee loading, a form of physical activity, has been found to mimic effects of voluntary exercise. Focusing on serotonergic signaling, we addressed a question: Does local mechanical loading to the skeleton elevate expression of tryptophan hydroxylase 2 (tph2) that is a rate-limiting enzyme for brain serotonin? A 5 min knee loading was applied to mice using 1 N force at 5 Hz for 1,500 cycles. A 5-min treadmill running was used as an exercise (positive) control, and a 90-min tail suspension was used as a stress (negative) control. Expression of tph2 was determined 30 min - 2 h in three brain regions --frontal cortex (FC), ventromedial hypothalamus (VMH), and brain stem (BS). We demonstrated for the first time that knee loading and treadmill exercise upregulated the mRNA level of tph2 in the BS, while tail suspension downregulated it. The protein level of tph2 in the BS was also upregulated by knee loading and downregulated by tail suspension. Furthermore, the downregulation of tph2 mRNA by tail suspension can be partially suppressed by pre-application of knee loading. The expression of tph2 in the FC and VMH was not significantly altered with knee loading. In this study we provided evidence that peripheral mechanical loading can activate central tph2 expression, suggesting that physical cues may mediate tph2-cathalyzed serotonergic signaling in the brain.


The rhox homeobox gene family shows sexually dimorphic and dynamic expression during mouse embryonic gonad development.
Reproductive capacity is fundamental to the survival of all species. Consequently, much research has been undertaken to better understand gametogenesis and the interplay between germ cells and the somatic cell lineages of the gonads. In this study, we have analyzed the embryonic expression pattern of the X-linked gene family Reproductive homeobox genes on the X chromosome (Rhox) in mice. Our data show that eight members of the Rhox gene family are developmentally regulated in sexually dimorphic and temporally dynamic patterns in the developing germ cells during early gonadogenesis. These changes coincide with critical stages of differentiation where the germ cells enter either mitotic arrest in the testis or meiotic arrest in the ovary. Finally, we show that Rhox8 (Tox) is the only member of the Rhox gene family that is expressed in the somatic compartment of the embryonic gonads. Our results indicate that the regulation of Rhox gene expression and its potential function during embryogenesis are quite distinct from those previously reported for Rhox gene regulation in postnatal gonads.


An early phase II study of oral S-1, a newly developed 5-fluorouracil derivative for advanced and recurrent gastrointestinal cancers. The S-1 Gastrointestinal Cancer Study Group.
5-Fluorouracil (5-FU) or a 5-FU derivative 1-(2-tetrahydrofuryl)-5-fluorouracil (FT) has been widely prescribed for patients with gastrointestinal cancer. However, the phosphorylation of 5-FU in the digestive tract causes gastrointestinal toxicities. 5-FU is also rapidly degraded to alpha-fluoro-beta-alanine after contact with dihydropyrimidine dehydrogenase (DPDase) which is mainly present in the liver. Therefore, to overcome these metabolic events, S-1, an antitumor agent was developed, based on the biochemical modulation of FT by 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo), in a molar ratio of 1:0.4:1. The antineoplastic effect of S-1, was examined in Japanese patients with advanced gastric (G) or colorectal (C) cancer in a multicenter early phase II study involving 24 centers throughout Japan. The patients were prescribed a minimum of 2 courses of S-1 orally, with each course consisting of 75 or 50 mg (in terms of FT) twice a day for 28 days followed by withdrawal for 2 weeks. Thirty-one patients with G and 31 C were entered into this study. The clinical response and extent of toxicity were evaluated in G 28 and C 30 cases, respectively. Nine (32.1%) G patients and 14 (46.7%) C patients had been treated previously with other anticancer drugs. In G patients, there was a 53.6% (15/28) and in C patients a 16.7% (5/30) response rate (90% confidence interval G 38.4-68.1% and C 8.4-30.5%) with 15 (53.6%) (G) and 5 (16.7%) (C) partial responses (PR), and these responses persisted for 79 days (G) and 120 days (C) (median value). In particular, the response rate for the primary lesion was 27.8% (5/18) (G) and 33.3% (1/3) (C). No change (NC) in the disease was observed in 4 (14.3%) (G) and 13 (43.3%) (C) patients, and in 6 (21. 4%) (G) and 7 (23.3%) (C) the disease progressed (PD). At the time of analysis, the median survival was 298 days (G) and 358 days (C). Major adverse effects consisted of gastrointestinal symptoms and myelosuppression while toxicities of grade 3 or more occurred in 35. 7% (10/28) (G) and 33.3% (10/30) (C). Based on these data, S-1 is considered to have positive effects in patients with advanced gastrointestinal cancer.


Event-related potential response to auditory social stimuli, parent-reported social communicative deficits and autism risk in school-aged children with congenital visual impairment.
Communication with visual signals, like facial expression, is important in early social development, but the question if these signals are necessary for typical social development remains to be addressed. The potential impact on social development of being born with no or very low levels of vision is therefore of high theoretical and clinical interest. The current study investigated event-related potential responses to basic social stimuli in a rare group of school-aged children with congenital visual disorders of the anterior visual system (globe of the eye, retina, anterior optic nerve). Early-latency event-related potential responses showed no difference between the VI and control group, suggesting similar initial auditory processing. However, the mean amplitude over central and right frontal channels between 280 and 320ms was reduced in response to own-name stimuli, but not control stimuli, in children with VI suggesting differences in social processing. Children with VI also showed an increased rate of autistic-related behaviours, pragmatic language deficits, as well as peer relationship and emotional problems on standard parent questionnaires. These findings suggest that vision may be necessary for the typical development of social processing across modalities.


Renal function and urate metabolism in late survivors with cyanotic congenital heart disease.
Diminished glomerular filtration rate, proteinuria, and large hypercellular congested glomeruli with segmental sclerosis are found in late survivors with cyanotic congenital heart disease (CCHD). Hyperuricemia is common, acute gouty arthritis is less common than uric acid levels would predict, and overt tophaceous deposits of uric acid are exceptional. The role of the kidney in causing the basic biochemical disturbances, and the relative importance of impaired urate excretion vs urate overproduction have not been established. Accordingly, we reviewed the courses of two index patients and prospectively studied eight additional CCHD patients from 28 years to 46 years old with mean hematocrits of (62 +/- 10%). Plasma creatinine concentration was normal (0.9 +/- 0.1 mg/dl) yet glomerular filtration rate was mildly reduced to 93 +/- 14 ml/min as measured by creatinine clearance and to 81 +/- 6 ml/min as measured by 111In DTPA. Three patients had significant proteinuria and one was nephrotic. Plasma uric acid concentration was high in all but one (8.2 +/- 2.1 mg/dl), mean 24 hr uric acid excretion was normal (564 +/- 221 mg), and fractional uric acid excretion was relatively low (6.3 +/- 2.6%). The two patients with highest plasma uric acid levels (12.0 and 10.2 mg/dl) had the lowest fractional excretions (2.8% and 4.0%). Both of these patients had diminished capacity to excrete a water load (38% and 27%/4 hr) and to maximally concentrate urine (520 and 635 mOsm/kg after water deprivation and vasopressin). In conclusion, high plasma uric acid levels in late survivors with CCHD are secondary to inappropriately low fractional uric acid excretion, not to urate overproduction.(ABSTRACT TRUNCATED AT 250 WORDS)


[5'-Nucleotidase as an "internal probe" in studying steroid hormone interaction with the plasma membranes of target cells].
Changes in the activity of 5'-nucleotidase, the marker enzyme of plasma membranes, in membrane cells of the uterus and liver were examined upon action of tropic and nontropic steroid hormones. In case of tropic steroids, the curves of changes in the activity with rise in the hormone concentration are complicated and broken with a marked minimum at 10(-8) M. Upon the action of nontropic hormones there takes place a monotonous rise in the enzymatic activity. The characteristic differences as shown by the curves make it possible to apply 5'-nucleotidase as endogenous probe during studies into hormone-membrane interactions.


Noncytotoxic suppression of human immunodeficiency virus type 1 transcription by exosomes secreted from CD8+ T cells.
CD8(+) T cells display a noncytotoxic activity that suppresses transcription of human immunodeficiency virus type 1 (HIV-1) in an antigen-independent and major histocompatibility complex-unrestricted manner. To date, the precise cellular and molecular factors mediating this CD8(+) T-cell effector function remain unsolved. Despite evidence indicating the dependence of the activity on cell-cell contact, the possibility of a membrane-mediated activity that represses transcription from the viral promoter remains unexplored. We therefore investigated whether this inhibition of HIV-1 transcription might be elicited by a membrane-bound determinant. Using a CD8(+) T-cell line displaying potent noncytotoxic HIV-1 suppression activity, we have identified a membrane-localized HIV-1-suppressing activity that is concomitantly secreted as 30- to 100-nm endosome-derived tetraspanin-rich vesicles known as exosomes. Purified exosomes from CD8(+) T-cell culture supernatant noncytotoxically suppressed CCR5-tropic (R5) and CXCR4-tropic (X4) replication of HIV-1 in vitro through a protein moiety. Similar antiviral activity was also found in exosomes isolated from two HIV-1-infected subjects. The antiviral exosomes specifically inhibited HIV-1 transcription in both acute and chronic models of infection. Our results, for the first time, indicate the existence of an antiviral membrane-bound factor consistent with the hallmarks defining noncytotoxic CD8(+) T-cell suppression of HIV-1.


A fast response variable optical attenuator based on blue phase liquid crystal.
Blue phase liquid crystals (BPLCs) are promising candidates for next generation display thanks to their fast response and quasi-isotropic optical properties. By taking these advantages, we propose to introduce the material into fiber-optic applications. As an example, a BPLC based variable optical attenuator (VOA) is demonstrated with a polarization independent design. The device shows normally-off feature when no field is applied. Response time down to submillisecond scale is achieved in switching between two arbitrary attenuation states. The attenuation range is also measured from 1480 to 1550 nm, which cover the whole telecomm S-band and part of the C-band. The overall performances reach the requirements for practical use; while still have room for further improvement. Through this example, the applicability of BPLC in fiber-optic devices is presented, which may impel the development of many other photonic applications from infrared to even microwave regions.


Recent developments in electronic medical records.
Human factors engineering principles will guide the development of future EMR systems. Physicians will use wireless palmtop computers to record patient data so that the computer does not come between the physician and patient in routine encounters. With few exceptions, the pieces for this type of system are available today, but not in one package. I believe EMR developers have recognized the ubiquity and power of the Internet. Because of advances in computers, software, and telecommunications reliability, solutions using thin-client technology will lower the cost of EMRs to physicians.


Ionic liquids as selectors for the enhanced detection of proteins.
Herein, we report an approach for protein detection enhanced by ionic liquid (IL) selectors in capillary electrophoresis (CE), with avidin as a model protein. Hydrophilic ILs were added into the running buffer of CE and acted as selectors for sample injection, enriching the positive target and excluding the negative from the capillary. When using 3 % (v/v) IL selector, the detection sensitivity of avidin was improved by over one order of magnitude, while the interference from protein adsorption was effectively avoided, even in an uncoated capillary. The electrochemiluminescence method was initially used for IL-based CE with low noise that was independent of the IL concentration, making ILs almost transparent as additives in the electrophoresis buffer.


Effect of ingestion of smokeless tobacco on motor distal latency of the median nerve.
Subjects were 17 men between the ages of 18 and 32 yr. and regular users of smokeless tobacco. Each subject received three treatments consisting of one pouch of Skoal Bandits, one pinch of their regular brand, and a nonnicotine piece of chewing gum. The nervous transmission at the neuromuscular junction in the right thumb was compared before treatment and once every minute for 15 min. after treatment. Repeated-measures analysis of variance indicated a significant increase in the distal latencies for both the brand-name grouping and in the regularly used brand. No such difference was found in a control group when compared to the pretest results. It was concluded that smokeless tobacco ingestion resulted in a delay in the nervous transmission across the neuromuscular junction. This delay was hypothesized to be caused by the enduring binding action of nicotine to the acetylcholine receptor sites, thereby blocking the impulse in some of the faster conducting nerve fibers.


Cost-effectiveness and safety of ramucirumab plus paclitaxel chemotherapy in the treatment of advanced and recurrent gastric cancer.
Introduction Weekly paclitaxel (PTX), irinotecan (CPT-11) and ramucirumab plus paclitaxel (Ram + PTX) are currently recommended as the standard second-line or later chemotherapies for advanced and recurrent gastric cancer. This study aims to compare the cost-effectiveness of using Ram + PTX vs. PTX or CPT-11. Furthermore, we investigated the safety and treatment continuity of Ram + PTX in Japan. Methods Expected costs were calculated based on data from patients with advanced and recurrent gastric cancer who were treated with PTX, CPT-11 and Ram + PTX. A literature review was performed to obtain clinical information so that the probability of the efficacy of each chemotherapy could be calculated. The cost-effectiveness ratio of each chemotherapy agent was calculated by dividing the expected cost by the median survival time (MST). Results The cost-effectiveness ratio per month was JPY 85,395.8/MST for the PTX regimen, JPY 132,735.4/MST for the CPT-11 regimen and JPY 657,175.4/MST for the Ram + PTX regimen (p < 0.001). The incremental cost-effectiveness ratio per month of the Ram + PTX regimen to the PTX regimen was JPY 2,780,432.4/MST. The incremental cost-effectiveness ratio of the Ram + PTX regimen to the CPT-11 regimen was JPY 2,185,179.0/MST. With regard to the reasons for discontinuation of treatment, the Ram + PTX regimen had only one case of being discontinued owing to adverse events, and had a profile similar to that of the PTX and CPT-11 regimens. Conclusion These findings show that the Ram + PTX regimen is less cost-effective compared to both the PTX and CPT-11 regimen, but the Ram + PTX regimen is a well-tolerated regimen with sufficient efficacy.


[Prevention of acute postoperative pancreatitis].
Results of an analysis of 4287 operations on organs of the abdomen have shown the frequency of acute pancreatitis after different surgical interventions to be 0,9%. This complication was more frequent after operations on the stomach (4,24%), less frequent after operations on biliary ducts (1,3%). Decompression of the biliary ducts and the gastro-intestinal tract reduced the frequency of acute pancreatitis after operations on the abdominal organs from 1,13% to 0,6%.


Effect of autophagy on multiple myeloma cell viability.
Because accumulation of potentially toxic malfolded protein may be extensive in immunoglobulin-producing multiple myeloma (MM) cells, we investigated the phenomenon of autophagy in myeloma, a physiologic process that can protect against malfolded protein under some circumstances. Autophagy in MM cell lines that express and secrete immunoglobulin and primary specimens was significantly increased by treatment with the endoplasmic reticulum stress-inducing agent thapsigargin, the mammalian target of rapamycin inhibitor rapamycin, and the proteasome inhibitor bortezomib. Inhibition of basal autophagy in these cell lines and primary cells by use of the inhibitors 3-methyladenine and chloroquine resulted in a cytotoxic effect that was associated with enhanced apoptosis. Use of small interfering RNA to knock down expression of beclin-1, a key protein required for autophagy, also inhibited viable recovery of MM cells. Because the data suggested that autophagy protected MM cell viability, we predicted that autophagy inhibitors would synergize with bortezomib for enhanced antimyeloma effects. However, the combination of these drugs resulted in an antagonistic response. In contrast, the autophagy inhibitor 3-methyladenine did synergize with thapsigargin for an enhanced cytotoxic response. These data suggest that autophagy inhibitors have therapeutic potential in myeloma but caution against combining such drugs with bortezomib.


What is below the support layer affects carbon nanotube growth: an iron catalyst reservoir yields taller nanotube carpets.
Here we demonstrate an approach to enhance the growth of vertically aligned carbon nanotubes (CNTs) by including a catalyst reservoir underneath the thin-film alumina catalyst underlayer. This reservoir led to enhanced CNT growth due to the migration of catalytic material from below the underlayer up to the surface through alumina pinholes during processing. This led to the formation of large Fe particles, which in turn influenced the morphology evolution of the catalytic iron surface layer through Ostwald ripening. With inclusion of this catalyst reservoir, we observed CNT growth up to 100% taller than that observed without the catalyst reservoir consistently across a wide range of annealing and growth durations. Imaging studies of catalyst layers both for different annealing times and for different alumina support layer thicknesses demonstrate that the surface exposure of metal from the reservoir leads to an active population of smaller catalyst particles upon annealing as opposed to a bimodal catalyst size distribution that appears without inclusion of a reservoir. Overall, the mechanism for growth enhancement we present here demonstrates a new route to engineering efficient catalyst structures to overcome the limitations of CNT growth processes.


[Changes in food availability in metropolitan Santiago Chile according to income (quintiles) 1988-1997].
Changes in household food availability from 1988-1997 obtained in a representative sample of Metropolitan Santiago were assessed; and related to observed changes in the epidemiological profile. We evaluated expenditures in food and beverages from the IV and V Household Expenditure Surveys conducted every 10 years by the National Institute of Statistics to calculate the Consumer Price Index. Food items were similarly grouped and expenditures from both surveys adjusted to concordance by assigning prices according to of food; the units consumed outside and at home were determined. Food expenditures increased, leading to greater food availability in all households and income categories; the increment was largest in the poorest quintiles. Apparent consumption of processed cereals, pastries and baked goods, poultry and pork, processed dairies, beverages and juices, dressings and mayonnaise, pre cooked meals and meals consumed "out of home" increased. Fish, vegetables and fruits increased slightly with a concomitant decrease in legumes. The present dietary pattern is also characterized by a greater availability of animal food products and processed foods; increased energy density, fat and saturated fat energy, sugars and high glycemic index foods; lower in phytochemicals, antioxidants, dietary fiber and omega-3 fatty acids. These changes are probably having a significant impact on the epidemiological and nutritional profile of the country; as manifested by an epidemic increase in obesity and chronic disease burden related to diet and physical inactivity.


Artefactual serum hyperkalaemia and hypercalcaemia in essential thrombocythaemia.
To investigate possible abnormalities of serum potassium and calcium levels in patients with essential thrombocythaemia and significant thrombocytosis. 24 cases of essential thrombocythaemia with significant thrombocytosis (platelet count > 700 x 10(9)/litre) had serum potassium and calcium estimations performed at the time of maximum thrombocytosis before treatment, and at the time of low platelet count after treatment with cytoreductive drugs. Selected patients were further investigated with plasma sampling and estimation of ionised calcium and parathyroid hormone. At the time of maximum thrombocytosis six patients had serum hyperkalaemia (> 5.5 mmol/litre) and five had serum hypercalcaemia (> 2.6 mmol/litre). Following treatment and reduction of the platelet count, hyperkalaemia resolved in all cases and hypercalcaemia in four of the five cases. Mean serum potassium and calcium concentrations were raised (p < 0.0001) at maximum thrombocytosis compared with the values when the platelet count was low. Serum potassium and calcium values were significantly correlated at all stages. Measurements on plasma consistently corrected the hyperkalaemia but not the hypercalcaemia. Serum hypercalcaemia was associated with raised ionised calcium and normal parathyroid hormone concentrations. Essential thrombocythaemia with significant thrombocytosis is associated with serum hyperkalaemia and hypercalcaemia. The probable mechanism of hypercalcaemia is the secretion of calcium in vitro from an excessive number of abnormally activated platelets. It is thus likely that the hypercalcaemia is an artefact, as is the hyperkalaemia.


Sex and Age Differences in Mortality in Southern China, 2004-2010.
The purpose of this study was to describe the mortality patterns in the southern provinces of China, and to provide epidemiologic data on sex and age differences of death outcomes. Reliable mortality and population data from January 2004 to December 2010 were obtained from 12 Disease Surveillance Point (DSP) sites in four provinces of China. Death data from all causes and respiratory disease, chronic obstructive pulmonary disease (COPD), pneumonia and influenza, circulatory disease, and ischemic heart disease, were stratified by year, month of death occurrence and sex, seven age groups, and summarized by descriptive statistics. The mean annual mortality rates of the selected 12 DSP sites in the southernmost provinces of China were 543.9 (range: 423.9-593.6) deaths per 100,000 population. The death rates show that noted sex differences were higher in the male population for all-cause, COPD and circulatory diseases. Pneumonia and influenza death rates present a different sex- and age-related distribution, with higher rates in male aged 65-74 years; whereas the death rates were opposite in elderly aged ≥75 years, and relatively higher in young children. This study had practical implications for recommending target groups for public health interventions.


Plasticity-stability dynamics during post-training processing of learning.
Learning continues beyond the end of training. Post-training learning is supported by changes in plasticity and stability in the brain during both wakefulness and sleep. However, the lack of a unified measure for assessing plasticity and stability dynamics during training and post-training periods has limited our understanding of how these dynamics shape learning. Focusing primarily on procedural learning, we integrate work using behavioral paradigms and a recently developed measure, the excitatory-to-inhibitory (E/I) ratio, to explore the delicate balance between plasticity and stability and its relationship to post-training learning. This reveals plasticity-stability cycles during both wakefulness and sleep that enhance learning and protect it from new learning during post-training processing.


Drug therapy in renal failure: dosing guidelines for adults. Part I: Antimicrobial agents, analgesics.
Data are presented in tabular form that provide guidelines for drug use in adult patients with renal insufficiency. The data are derived from the current medical literature. If specific information about a drug is unavailable or conflicting, emphasis is given to normal pharmacokinetic variables in arriving at recommendations for therapy. Nephrotoxicity or adverse effects in patients with renal disease are noted and adjustments for dialysis suggested.


The role of body mass index at diagnosis of colorectal cancer on Black-White disparities in survival: a density regression mediation approach.
The study of racial/ethnic inequalities in health is important to reduce the uneven burden of disease. In the case of colorectal cancer (CRC), disparities in survival among non-Hispanic Whites and Blacks are well documented, and mechanisms leading to these disparities need to be studied formally. It has also been established that body mass index (BMI) is a risk factor for developing CRC, and recent literature shows BMI at diagnosis of CRC is associated with survival. Since BMI varies by racial/ethnic group, a question that arises is whether differences in BMI are partially responsible for observed racial/ethnic disparities in survival for CRC patients. This article presents new methodology to quantify the impact of the hypothetical intervention that matches the BMI distribution in the Black population to a potentially complex distributional form observed in the White population on racial/ethnic disparities in survival. Our density mediation approach can be utilized to estimate natural direct and indirect effects in the general causal mediation setting under stronger assumptions. We perform a simulation study that shows our proposed Bayesian density regression approach performs as well as or better than current methodology allowing for a shift in the mean of the distribution only, and that standard practice of categorizing BMI leads to large biases when BMI is a mediator variable. When applied to motivating data from the Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium, our approach suggests the proposed intervention is potentially beneficial for elderly and low-income Black patients, yet harmful for young or high-income Black populations.


[Adaptation of the central nervous system to optical correction].
Wearing spectacles imply an adjustment of the visual perception and eye movements. The visual cortex accounts for this plasticity, including at the adulthood, especially by the shift or the sprading of the receptor fields and the adjustment of the sensitivity of the primary visual cortex cells to spatial orientation and movement. The cerebellum modulates the vestibulo-ocular reflex gain. The adjustment latencies range from a few minutes to several days according to the disturbancy severity, the drug interferences and the age and medical history of the subject. Neurotrophins seem to be essential for this adjustment and might become an efficient tool to extend the plasticity period.


Postchemotherapy adjuvant tamoxifen therapy beyond five years in patients with lymph node-positive breast cancer. Eastern Cooperative Oncology Group.
Data from a pilot study published in 1984 suggested that tamoxifen administration (as adjuvant hormonal therapy) for more than 5 years after initial breast cancer surgery might have therapeutic benefit. A randomized trial was performed to assess the efficacy of maintaining tamoxifen therapy beyond 5 years in women with axillary lymph node-positive breast cancer who had been treated with surgery followed by 1 year of chemotherapy and 5 years of tamoxifen. One hundred ninety-four women (87 postmenopausal and 107 premenopasual) enrolled in two concurrent Eastern Cooperative Oncology Group adjuvant trials (E4181 for postmenopausal patients and E5181 for premenopausal patients) were randomly assigned to continued tamoxifen therapy or observation. Data for 193 women (87 postmenopausal and 106 premenopausal) were available for analysis. Median follow-up is 5.6 years since the randomization at 5 years, with the longest follow-up being 8.0 years. The major analyses measured events from the time of randomization until relapse or death; these included time-to-relapse analyses, with new opposite-breast cancers counted as treatment failures, and survival analyses. Time-to-relapse comparisons and survival comparisons for women in the two treatment groups were made by use of the Kaplan-Meier method and the logrank test. Reported P values are two-sided. Five years after the randomization, no statistically significant differences were noted in either time to relapse or survival between women continuing to receive tamoxifen and those on observation. Eight-five percent of the women receiving tamoxifen were disease free at this time compared with 73% of those on observation (P = .10); survival was 86% for those continuing to receive tamoxifen and 89% for those on observation (P = .52). Differences in the time to relapse and survival between premenopausal and postmenopausal women assigned to the two treatment groups were also not statistically significant (time to relapse: P = .38 and P = .16 for premenopausal and postmenopausal patients, respectively; survival; P = .18 and P = .72 for premenopausal and postmenopausal patients, respectively). There was an indication that women with estrogen receptor-positive tumors may experience a longer time to relapse with continued tamoxifen therapy (P = .014); however, the survival difference for this subgroup was not statistically significant (P = .81). The toxicity patterns in the two treatment groups were similar. Our results suggest that further evaluation of adjuvant tamoxifen therapy beyond 5 years in women with axillary lymph node-positive, estrogen receptor-positive breast cancer who have also been treated with adjuvant chemotherapy would be appropriate.


Measurement of Proton Spin Diffusivity in Hydrated Cementitious Solids.
The study of hydration and crystallization processes involving inorganic oxides is often complicated by poor long-range order and the formation of heterogeneous domains or surface layers. In solid-state NMR, 1H-1H spin diffusion analyses can provide information on spatial composition distributions, domain sizes, or miscibility in both ordered and disordered solids. Such analyses have been implemented in organic solids but crucially rely on separate measurements of the 1H spin diffusion coefficients in closely related systems. We demonstrate that an experimental NMR method, in which "holes" of well-defined dimensions are created in proton magnetization, can be applied to determine spin diffusion coefficients in cementitious solids hydrated with 17O-enriched water. We determine proton spin diffusion coefficients of 240 ± 40 nm2/s for hydrated tricalcium aluminate and 140 ± 20 nm2/s for hydrated tricalcium silicate under quasistatic conditions.


Consistency of the disposition index in the face of diet induced insulin resistance: potential role of FFA.
Insulin resistance induces hyperinsulinemic compensation, which in turn maintains almost a constant disposition index. However, the signal that gives rise to the hyperinsulinemic compensation for insulin resistance remains unknown. In a dog model of obesity we examined the possibility that potential early-week changes in plasma FFA, glucose, or both could be part of a cascade of signals that lead to compensatory hyperinsulinemia induced by insulin resistance. Hypercaloric high fat feeding in dogs resulted in modest weight gain, and an increase in adipose tissue with no change in the non-adipose tissue size. To compensate for the drop in insulin sensitivity, there was a significant rise in plasma insulin, which can be attributed in part to a decrease in the metabolic clearance rate of insulin and increased insulin secretion. In this study we observed complete compensation for high fat diet induced insulin resistance as measured by the disposition index. The compensatory hyperinsulinemia was coupled with significant changes in plasma FFAs and no change in plasma glucose. We postulate that early in the development of diet induced insulin resistance, a change in plasma FFAs may directly, through signaling at the level of β-cell, or indirectly, by decreasing hepatic insulin clearance, result in the observed hyperinsulinemic compensation.


The Effect of Augmenting OPTN Data With External Death Data on Calculating Patient Survival Rates After Organ Transplantation.
Although the Organ Procurement and Transplantation Network (OPTN) database contains a rich set of data on United States transplant recipients, follow-up data may be incomplete. It was of interest to determine if augmenting OPTN data with external death data altered patient survival estimates. Solitary kidney, liver, heart, and lung transplants performed between January 1, 2011, and January 31, 2013, were queried from the OPTN database. Unadjusted Kaplan-Meier 3-year patient survival rates were computed using 4 nonmutually exclusive augmented datasets: OPTN only, OPTN + verified external deaths, OPTN + verified + unverified external deaths (OPTN + all), and an additional source extending recipient survival time if no death was found in OPTN + all (OPTN + all [Assumed Alive]). Pairwise comparisons were made using unadjusted Cox Proportional Hazards analyses applying Bonferroni adjustments. Although differences in patient survival rates across data sources were small (≤1 percentage point), OPTN only data often yielded slightly higher patient survival rates than sources including external death data. No significant differences were found, including comparing OPTN + verified (hazard ratio [HR], 1.05; 95% confidence interval [95% CI], 1.00-1.10); P = 0.0356), OPTN + all (HR, 1.06; 95% CI, 1.01-1.11; P = 0.0243), and OPTN + all (Assumed Alive) (HR, 1.00; 95% CI, 0.96-1.05; P = 0.8587) versus OPTN only, or OPTN + verified (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0511), and OPTN + all (HR, 1.05; 95% CI, 1.00-1.10; P = 0.0353) versus OPTN + all (Assumed Alive). Patient survival rates varied minimally with augmented data sources, although using external death data without extending the survival time of recipients not identified in these sources results in a biased estimate. It remains important for transplant centers to maintain contact with transplant recipients and obtain necessary follow-up information, because this information can improve the transplantation process for future recipients.


Ocular Pulse Amplitude in Non-Diabetic Patients with End Stage Renal Disease and Normal Individuals Using Dynamic Contour Tonometry.
Ocular Pulse Amplitude (OPA) is the fluctuation of IOP with the cardiac cycle which is equal to the difference between systolic and diastolic IOP. These variations in IOP are thought to be caused by the blood volume that is pumped into the eye, mainly the choroidal bed during each cardiac cycle. In patients with end stage renal disease (ESRD), Choroidal perfusion has been found to be reduced as determined by Indocyanine Green Angiography (ICG) which is an invasive procedure. OPA is recorded by Dynamic Contour Tonometer (DCT) which represents a potential new technology for measuring choroidal blood flow indirectly & non-invasively especially in patients with suspected compromise in perfusion as in ESRD. In this study we postulate that measurement of OPA can be used to assess the choroidal perfusion inpatients with ESRD. To measure OPA in non-diabetic patients with ESRD on hemodialysis and to compare it with that of OPA in age matched normal individuals. It was a prospective Cross-sectional study and was done in a clinical set up during the period of January 2013 to October 2013. OPA among 44exposed and 44 non exposed individuals were measured using Dynamic Contour Tonometry (DCT) and analysis done. The mean OPA in non diabetic patients with ESRD was 1.945mm Hg (CI:1.847 - 2.043) and the mean OPA in age matched normals was 2.16mm Hg (CI: 2.08- 2.24). OPA in non diabetic ESRD patients was statistically significantly lower than that of age matched normals (p=0.03). There was no correlation between OPA and other parameters like age, gender, intraocular pressure, blood pressure or serumcreatinine levels.


Alkalithermophiles.
Alkalithermophiles are an exciting subset of extremophilic organisms and represent extremophiles that are adapted to two extreme conditions, i.e. to a combination of alkaline and thermobiotic growth conditions. Among the anaerobic alkalithermophiles are representatives of both Bacteria and Archaea within a wide variety of physiological types and systematic groups, although a great majority belongs to the Firmicutes. Alkaliphiles have been isolated from a variety of niches including mesobiotic and neutrophilic soils and sediments. Interestingly anaerobic isolates from mesobiotic and neutrophilic niches exhibit shorter doubling times than isolates from thermobiotic niches; some anaerobic alkalithermophiles exhibit extremely fast growth rates, i.e. doubling times as short as 10 min. Their adaptation to both high pH and high temperature draws our attention not only because they are potential sources of industrially valuable enzymes but also because of their adaptive mechanisms to external environmental parameters. They could thus function as model organisms for extraterrestrial life in some environments and for theories on the origin of life. Alkalithermophiles, as far we know, do not represent the most thermophilic nor the most alkaliphilic of micro-organisms but represent the most alkaliphilic ones among the thermophiles and vice versa. We believe that the presently known species are only the tip of the iceberg and therefore that they do not represent the true boundaries under which life can thrive in respect to high temperature in alkaline environments.


Respiratory tract allergic disease and atopy: experimental evidence for a fungal infectious etiology.
Allergic asthma is an obstructive lung disease linked to environmental exposures that elicit allergic airway inflammation and characteristic antigen-specific immunoglobulin reactions termed atopy. Analyses of asthma pathogenesis using experimental models have shown that T helper cells, especially T helper type 2 (Th2) cells and Th2 cytokines such as interleukin 4 (IL-4) and IL-13, are critical mediators of airway obstruction following allergen challenge, but the environmental initiators of lung Th2 responses are less defined. Our studies demonstrate that fungal-derived proteinases that are commonly found in home environments are requisite immune adjuvants capable of eliciting robust Th2 responses and allergic lung disease in mice. We have further shown that common household fungi readily infect the mouse respiratory tract and induce both asthma-like disease and atopy to otherwise innocuous bystander antigens through the secretion of proteinases. These findings support the possibility that asthma and atopy represent a reaction to respiratory tract fungal infection, suggesting novel means for diagnosis and therapy of diverse allergic disorders.


Comparative Analysis of Structural Variations Due to Genome Shuffling of Bacillus Subtilis VS15 for Improved Cellulase Production.
Cellulose is one of the most abundant and renewable biomass products used for the production of bioethanol. Cellulose can be efficiently hydrolyzed by Bacillus subtilis VS15, a strain isolate obtained from decomposing logs. A genome shuffling approach was implemented to improve the cellulase activity of Bacillus subtilis VS15. Mutant strains were created using ethyl methyl sulfonate (EMS), N-Methyl-N' nitro-N-nitrosoguanidine (NTG), and ultraviolet light (UV) followed by recursive protoplast fusion. After two rounds of shuffling, the mutants Gb2, Gc8, and Gd7 were produced that had an increase in cellulase activity of 128%, 148%, and 167%, respectively, in comparison to the wild type VS15. The genetic diversity of the shuffled strain Gd7 and wild type VS15 was compared at whole genome level. Genomic-level comparisons identified a set of eight genes, consisting of cellulase and regulatory genes, of interest for further analyses. Various genes were identified with insertions and deletions that may be involved in improved celluase production in Gd7.. Strain Gd7 maintained the capability of hydrolyzing wheatbran to glucose and converting glucose to ethanol by fermentation with Saccharomyces cerevisiae of the wild type VS17. This ability was further confirmed by the acidified potassium dichromate (K2Cr2O7) method.


Class III correction using an inter-arch spring-loaded module.
A retrospective study was conducted to determine the cephalometric changes in a group of Class III patients treated with the inter-arch spring-loaded module (CS2000®, Dynaflex, St. Ann, MO, USA). Thirty Caucasian patients (15 males, 15 females) with an average pre-treatment age of 9.6 years were treated consecutively with this appliance and compared with a control group of subjects from the Bolton-Brush Study who were matched in age, gender, and craniofacial morphology to the treatment group. Lateral cephalograms were taken before treatment and after removal of the CS2000® appliance. The treatment effects of the CS2000® appliance were calculated by subtracting the changes due to growth (control group) from the treatment changes. All patients were improved to a Class I dental arch relationship with a positive overjet. Significant sagittal, vertical, and angular changes were found between the pre- and post-treatment radiographs. With an average treatment time of 1.3 years, the maxillary base moved forward by 0.8 mm, while the mandibular base moved backward by 2.8 mm together with improvements in the ANB and Wits measurements. The maxillary incisor moved forward by 1.3 mm and the mandibular incisor moved forward by 1.0 mm. The maxillary molar moved forward by 1.0 mm while the mandibular molar moved backward by 0.6 mm. The average overjet correction was 3.9 mm and 92% of the correction was due to skeletal contribution and 8% was due to dental contribution. The average molar correction was 5.2 mm and 69% of the correction was due to skeletal contribution and 31% was due to dental contribution. Mild to moderate Class III malocclusion can be corrected using the inter-arch spring-loaded appliance with minimal patient compliance. The overjet correction was contributed by forward movement of the maxilla, backward and downward movement of the mandible, and proclination of the maxillary incisors. The molar relationship was corrected by mesialization of the maxillary molars, distalization of the mandibular molars together with a rotation of the occlusal plane.


Teat scores in first-parity Gelbvieh cows: relationship with suspensory score and calf growth traits.
Teat and udder suspensory scores from 9,418 first-parity Gelbvieh cows and growth records from 19,119 calves were used to estimate genetic and environmental parameters for teat and suspensory score and to investigate the relationship of teat and suspensory score with calf growth traits and maternal genetic growth effects. First-parity cows did not have multiple records within 280 d, gave birth to one calf, were 4 yr of age or younger at first-calving, and were at least 50% Gelbvieh. Producers scored cows within 24 h of parturition. Teat score (T), a subjective measure of teat size, ranged from 0 (very large) to 50 (very small), and suspensory score (S), a subjective score of udder support, ranged from 0 (very pendulous) to 50 (very tight). Unadjusted birth weight (BW), weaning weight, and yearling weight of the calves, born in the first three parities to cows with first-parity T and S records, were used to calculate pre- and postweaning ADG (WG and YG, respectively). A mixed model was used for the multiple trait analysis of T, S, BW, WG, and YG, which included herd-year, month of calving, age of cow at calving, and sex of calf (included only for BW, WG, and YG) as systematic effects; regression on the percentage of Gelbvieh; and additive animal and maternal genetic of dam (included only for BW and WG), maternal permanent environment (included only for BW and WG), and residual as random effects. The genetic correlation between T and S was 0.95, suggesting that T and S are basically the same trait in this dataset. The genetic correlations between T (S) with direct BW, WG, and YG and with maternal BW and WG were -0.18 (-0.06), 0.38 (0.31), 0.09 (-0.01), -0.16 (-0.16), and -0.47 (-0.55), respectively, suggesting that cows with smaller teats and tighter udders produced less milk and raised calves that had higher genetic growth potential for WG. Further, the Pearson correlations between predicted breeding values of T and S with maternal WG indicated that animals with extremely large teats or pendulous udders may produce more milk, but that the calf may have trouble accessing it. Conversely, with extremely small teats or tight udders, smaller amounts of milk would be produced and there may be a problem producing enough milk to maintain the growing calfs maintenance requirements. Therefore, it may be more beneficial for producers to select animals that have intermediate breeding values for T and S.


Spatiotemporal expression and functional implication of CXCL14 in the developing mice cerebellum.
Cerebellar granule neurons migrate from the external granule cell layer (EGL) to the internal granule cell layer (IGL) during postnatal morphogenesis. This migration process through 4 different layers is a complex mechanism which is highly regulated by many secreted proteins. Although chemokines are well-known peptides that trigger cell migration, but with the exception of CXCL12, which is responsible for prenatal EGL formation, their functions have not been thoroughly studied in granule cell migration. In the present study, we examined cerebellar CXCL14 expression in neonatal and adult mice. CXCL14 mRNA was expressed at high levels in adult mouse cerebellum, but the protein was not detected. Nevertheless, Western blotting analysis revealed transient expression of CXCL14 in the cerebellum in early postnatal days (P1, P8), prior to the completion of granule cell migration. Looking at the distribution of CXCL14 by immunohistochemistry revealed a strong immune reactivity at the level of the Purkinje cell layer and molecular layer which was absent in the adult cerebellum. In functional assays, CXCL14 stimulated transwell migration of cultured granule cells and enhanced the spreading rate of neurons from EGL microexplants. Taken together, these results revealed the transient expression of CXCL14 by Purkinje cells in the developing cerebellum and demonstrate the ability of the chemokine to stimulate granule cell migration, suggesting that it must be involved in the postnatal maturation of the cerebellum.


Quality improvement in neurology residency programs. Report of the Quality Improvement Committee of the Association of University Professors of Neurology.
The neurology residency programs in the United States are facing a crisis of quality. The Association of University Professors of Neurology (AUPN) approved the Quality Improvement Committee to examine this situation and make recommendations, which have been accepted by the AUPN. The recommendations are (1) that the educational goals of neurology residency training be dissociated from patient-care needs in academic medical centers and (2) that minimum levels of quality be applied to residents in neurology residency programs and to these programs themselves. These minimum criteria should include minimum educational criteria for entry into the program, minimum criteria for advancement from one year to the next in the program, and minimum criteria for performance of the graduates of neurology residency programs for program accreditation. The implementation of these recommendations will require a shift of funding of the care of indigent patients from the graduate medical education budget to direct patient-care sources. These recommendations will significantly improve the quality of neurologists and neurologic care in the United States.


Healthy life-style promoting behaviour in Turkish women aged 18-64.
In this study we aimed to investigate the healthy life-style behaviour of Turkish women and establish influencing features. This descriptive study performed by a questionnaire method was conducted in a primary health care centre, in an urban region in Kayseri, Turkey. Every midwife region belonging to the health care centre was accepted as a cluster, and a sample of 450 women between ages 18-64, was gathered from 9 midwife regions. The Health Promotion Life-style Profile (HPLP) was applied to evaluated the healthy life- style behaviour of 421 women that could be reached. T test, Tukey HSD with ANOVA, and chi square tests were used for analysis. The mean total HPLP was 126.8 ± 19.2 (interpersonal support subscale, 74.3 ± 14.1; nutrition subscale, 73.6 ± 12.6; self-actualisation subscale, 70.6 ± 11.9; stress management subscale, 63.4 ± 13.0; health responsibility subscale, 61.2 ± 13.2; and exercise subscale, 47.1 ± 15.0). There was no statistically significant variation when evaluated for age, marital state, family type, economic status, and perception of self-health, smoking, and BMI. HPLP was high in people with an education of primary school and lower in university graduates, in people who lived mostly in the city centre and in individuals with chronic diseases. In conclusion, it was established that the health promoting behaviour in Turkish women is, in general, at a medium level, and women should be enlightened in order to develop and increase the habit of health preservation and promotion.


A novel method for assessing arterial stiffness by a hydrostatic approach.
Arterial stiffness is an important index for cardiovascular events. The objective of this study is to examine possible parameters related to arterial stiffness that can be estimated during simple arm movements. An experiment was conducted on 32 subjects divided into two groups, one with an age of 26+/-4 years old, and the other 61+/-9. The pulse transit time measured from electrocardiogram to finger photoplethysmogram (PPG) and the amplitude of PPG were calculated beat-to-beat for the subjects while they had their arms lowered. The results of the study showed that the ratio between percentage changes in PTT and finger height are significantly different for the two groups of subjects with different age and health conditions, indicating that parameters can be potentially extracted from this procedure to represent the difference in arterial stiffness of the two groups of subjects.


The normal foot.
The term "normal foot" has many different interpretations. This article reviews some of the ways in which the word "normal" has been used historically to describe the foot. Also discussed are the problems of attempting to determine what should constitute a normal foot and proposed criteria for distinguishing between the normal and the pathological.


An integrated PK/PD model investigating the impact of tumor size and systemic safety on animal survival in SW1990 pancreatic cancer xenograft.
Survival is one of the most important endpoints in cancer therapy, and parametric survival analysis could comprehensively reveal the overall result of disease progression, drug efficacy, toxicity as well as their interactions. In this study we investigated the efficacy and toxicity of dexamethasone (DEX) combined with gemcitabine (GEM) in pancreatic cancer xenograft. Nude mice bearing SW1990 pancreatic cancer cells derived tumor were treated with DEX (4 mg/kg, i.g.) and GEM (15 mg/kg, i.v.) alone or in combination repeatedly (QD, Q3D, Q7D) until the death of animal or the end of study. Tumor volumes and net body weight (NBW) were assessed every other day. Taking NBW as a systemic safety indicator, an integrated pharmacokinetic/pharmacodynamic (PK/PD) model was developed to quantitatively describe the impact of tumor size and systemic safety on animal survival. The PK/PD models with time course data for tumor size and NBW were established, respectively, in a sequential manner; a parametric time-to-event (TTE) model was also developed based on the longitudinal PK/PD models to describe the survival results of the SW1990 tumor-bearing mice. These models were evaluated and externally validated. Only the mice with good tumor growth inhibition and relatively stable NBW had an improved survival result after DEX and GEM combination therapy, and the simulations based on the parametric TTE model showed that NBW played more important role in animals' survival compared with tumor size. The established model in this study demonstrates that tumor size was not always the most important reason for cancer-related death, and parametric survival analysis together with safety issues was also important in the evaluation of oncology therapies in preclinical studies.


Cathepsin inhibition-induced lysosomal dysfunction enhances pancreatic beta-cell apoptosis in high glucose.
Autophagy is a lysosomal degradative pathway that plays an important role in maintaining cellular homeostasis. We previously showed that the inhibition of autophagy causes pancreatic β-cell apoptosis, suggesting that autophagy is a protective mechanism for the survival of pancreatic β-cells. The current study demonstrates that treatment with inhibitors and knockdown of the lysosomal cysteine proteases such as cathepsins B and L impair autophagy, enhancing the caspase-dependent apoptosis of INS-1 cells and islets upon exposure to high concentration of glucose. Interestingly, treatment with cathepsin B and L inhibitors prevented the proteolytic processing of cathepsins B, D and L, as evidenced by gradual accumulation of the respective pro-forms. Of note, inhibition of aspartic cathepsins had no effect on autophagy and cell viability, suggesting the selective role of cathepsins B and L in the regulation of β-cell autophagy and apoptosis. Lysosomal localization of accumulated pro-cathepsins in the presence of cathepsin B and L inhibitors was verified via immunocytochemistry and lysosomal fractionation. Lysotracker staining indicated that cathepsin B and L inhibitors led to the formation of severely enlarged lysosomes in a time-dependent manner. The abnormal accumulation of pro-cathepsins following treatment with inhibitors of cathepsins B and L suppressed normal lysosomal degradation and the processing of lysosomal enzymes, leading to lysosomal dysfunction. Collectively, our findings suggest that cathepsin defects following the inhibition of cathepsin B and L result in lysosomal dysfunction and consequent cell death in pancreatic β-cells.


Investigation of blast-induced traumatic brain injury.
Many troops deployed in Iraq and Afghanistan have sustained blast-related, closed-head injuries from being within non-lethal distance of detonated explosive devices. Little is known, however, about the mechanisms associated with blast exposure that give rise to traumatic brain injury (TBI). This study attempts to identify the precise conditions of focused stress wave energy within the brain, resulting from blast exposure, which will correlate with a threshold for persistent brain injury. This study developed and validated a set of modelling tools to simulate blast loading to the human head. Using these tools, the blast-induced, early-time intracranial wave motions that lead to focal brain damage were simulated. The simulations predict the deposition of three distinct wave energy components, two of which can be related to injury-inducing mechanisms, namely cavitation and shear. Furthermore, the results suggest that the spatial distributions of these damaging energy components are independent of blast direction. The predictions reported herein will simplify efforts to correlate simulation predictions with clinical measures of TBI and aid in the development of protective headwear.


Photophysical and photochemical properties of 1,2,4-trihydroxy-9,10-anthraquinone adsorbed on inorganic oxides.
The photophysical and photochemical properties of 1,2,4-trihydroxy-9,10-anthraquinone (purpurin) adsorbed on three inorganic oxides (SiO2, Al2O3 and TiO2) were compared with those shown by the same molecule in solution and in solid phase. In particular, steady-state (absorption and fluorescence) and transient (laser flash photolysis) techniques were used to characterize the lowest excited singlet and triplet states together with the transients (ketyl radicals and cation radicals) formed through the primary decay processes of the excited states of purpurin both in solution and adsorbed on the oxide surfaces, TiO2 is particularly efficient to sensitize the oxidation of purpurin and to form colourless photoproducts, while purpurin absorbed on SiO2 and Al2O3 is much more stable. This is related to the ability of the solid matrix to induce the formation of the purpurin cation radical and to direct its decay towards reactive channels.


Comparison between small radiation therapy electron beams collimated by Cerrobend and tubular applicators.
The purpose of this study was to compare the dosimetric properties of small field electron beams shaped by circular Cerrobend blocks and stainless steel tubular applicators. Percentage depth dose curves, beam profiles, and output factors of small-size circular fields from 2 to 5 cm diameter, obtained either by tubular applicators and Cerrobend blocks, were measured for 6, 10, and 15 MeV electron beam energies. All measurements were performed using a PTW microDiamond 60019 premarket prototype. An overall similar behavior between the two collimating systems can be observed in terms of PDD and beam profiles. However, Cerrobend collimators produce a higher bremsstrahlung background under irradiation with high-energy electrons. In such irradiation condition, larger output factors are observed for tubular applicators. Similar dosimetric properties are observed using circular Cerrobend blocks and stainless steel tubular applicators at lower beam energies. However, Cerrobend collimators allow the delivery of specific beam shapes, conformed to the target area. On the other hand, in high-energy irradiation conditions, tubular applicators produce a lower bremsstrahlung contribution, leading to lower doses outside the target volume. In addition, the higher output factors observed at high energies for tubular applicators lead to reduced treatment times.


Current perspectives on invasive nontyphoidal Salmonella disease.
We searched PubMed for scientific literature published in the past 2 years for relevant information regarding the burden of invasive nontyphoidal Salmonella disease and host factors associated with nontyphoidal Salmonella infection and discuss current knowledge on vaccine development. The following search terms were used: Salmonella, non typhoidal/nontyphoidal, NTS, disease, bloodstream infection, invasive, sepsis/septicaemia/septicemia, bacteraemia/bacteremia, gastroenteritis, incidence, prevalence, morbidity, mortality, case fatality, host/risk factor, vaccination, and prevention/control. Estimates of the global invasive nontyphoidal Salmonella disease burden have been recently updated; additional data from Africa, Asia, and Latin America are now available. New data bridge various knowledge gaps, particularly with respect to host risk factors and the geographical distribution of iNTS serovars. It has also been observed that Salmonella Typhimurium sequence type 313 is emergent in several African countries. Available data suggest that genetic variation in the sequence type 313 strain has led to increased pathogenicity and human host adaptation. A bivalent efficacious vaccine, targeting Salmonella serovars Typhimurium and Enteritidis, would significantly lower the disease burden in high-risk populations. The mobilization of surveillance networks, especially in Asia and Latin America, may provide missing data regarding the invasive nontyphoidal Salmonella disease burden and their corresponding antimicrobial susceptibility profiles. Efforts and resources should be directed toward invasive nontyphoidal Salmonella disease vaccine development.


Secondary infections in patients with atopic dermatitis.
Clinicians have long since been aware that bacteria and other microorganisms play a role in the etiology of atopic dermatitis. Indeed, the immunological profile of atopy favors colonization by Staphylococcus aureus, and the bacteria are present in most patients with atopic dermatitis, even in the absence of skin lesions. Clinical signs of impetiginization, such as weeping and crusting, periauricular fissuration, or small superficial pustules are a sensitive indicator that the numbers of S. aureus may have increased and a clinical indication of secondary infected dermatitis. However, recent research that has focussed on the role of S. aureus in atopic dermatitis, offers a reversed perspective, by presenting evidence that the underlying pathology of atopic dermatitis, i.e. an alteration of the skin barrier and inflammation of the upper dermis, depends itself on the presence of an infectious process. In other words, secondary infection with S. aureus emerges as a cause of atopic dermatitis. Secondary infections due to fungi have, comparatively, received less attention, but there is evidence for a role for Malassezia spp. as a factor in dermatitis with a head and neck distribution pattern. Viral infections, such as herpes simplex virus, and mixed infections of intertriginous spaces, may complicate an underlying atopic dermatitis, but are not perceived as etiologic factors. Recent research has greatly contributed to our understanding of the pathophysiological potential of S.aureus superantigens in atopic dermatitis, suggesting that antibiotic therapy might be an important element in the therapeutic management of atopic dermatitis. At present, however, the clinical evidence is scarce with regards to demonstrating a clear advantage of combined anti-inflammatory and antibiotic treatment, compared with anti-inflammatory treatment alone. If there is a consensus that the presence of clinically infected lesions in atopic dermatitis warrants a course of specific antibiotic topical therapy, the clinical benefit of antibiotic agents in apparently uninfected atopic dermatitis, as present in the majority of patients, remains an open question.Moreover, the impact of adjuvant skin care on the cutaneous microflora needs to be quantified in order to properly assess the role of specific antibiotic therapy in clinically uninfected atopic dermatitis. In the meantime, secondary infections in atopic dermatitis remain a secondary problem in clinical atopic dermatitis management, and specific anti-infective therapy remains a method of fine-tuning for optimizing individual atopic dermatitis treatment.


Acute hemodynamic effects of bisoprolol, a new beta 1 selective adrenoreceptor blocking agent, in patients with coronary artery disease.
To assess acute hemodynamic effects of the new beta-adrenergic blocking drug bisoprolol with experimentally documented beta 1 selectivity, we studied 16 patients with stable angina and angiographically proven coronary artery disease. Simultaneous right heart catheterization and radionuclide angiocardiography were performed at rest and during exercise without treatment (control) and 2 h after 5 mg bisoprolol (6 patients) and 20 mg bisoprolol (10 patients), respectively, administered perorally. The hemodynamic profile of bisoprolol was similar to that previously described after acute beta-blockade. A negative chronotropic effect occurred after 5 mg bisoprolol at rest, but the negative inotropic changes did not reach significance, whereas cardiac index decreased and total vascular resistance increased after 20 mg bisoprolol. During exercise, negative inotropic and blood-pressure-lowering effects were present after both dosages, resulting in improved myocardial oxygen consumption as reflected by a significantly reduced rate pressure product. Because ejection fraction and pulmonary capillary wedge pressure were not significantly changed even after the 20 mg dose, bisoprolol has only mild negative inotropic effects and seems hemodynamically safe.


Mindfulness Meditation for Fibromyalgia: Mechanistic and Clinical Considerations.
Fibromyalgia is a disorder characterized by widespread pain and a spectrum of psychological comorbidities, rendering treatment difficult and often a financial burden. Fibromyalgia is a complicated chronic pain condition that requires a multimodal therapeutic approach to optimize treatment efficacy. Thus, it has been postulated that mind-body techniques may prove fruitful in treating fibromyalgia. Mindfulness meditation, a behavioral technique premised on non-reactive sensory awareness, attenuates pain and improves mental health outcomes. However, the impact of mindfulness meditation on fibromyalgia-related outcomes has not been comprehensively characterized. The present review delineates the existing evidence supporting the effectiveness and hypothesized mechanisms of mindfulness meditation in treating fibromyalgia-related outcomes. Mindfulness-based interventions premised on cultivating acceptance, non-attachment, and social engagement may be most effective in decreasing fibromyalgia-related pain and psychological symptoms. Mindfulness-based therapies may alleviate fibromyalgia-related outcomes through multiple neural, psychological, and physiological processes. Mindfulness meditation may provide an effective complementary treatment approach for fibromyalgia patients, especially when combined with other reliable techniques (exercise; cognitive behavioral therapy). However, characterizing the specific analgesic mechanisms supporting mindfulness meditation is a critical step to fostering the clinical validity of this technique. Identification of the specific analgesic mechanisms supporting mindfulness-based pain relief could be utilized to better design behavioral interventions to specifically target fibromyalgia-related outcomes.


Epilepsy care in developing countries: part I of II.
Although 80% of people with epilepsy reside in resource poor, developing countries, epilepsy care in these regions remains limited and the majority of epilepsy patients go untreated. Cost-effective, sustainable epilepsy care services, delivering first-line antiepileptic drugs through established primary health care facilities, are needed to decrease these treatment gaps. Neurologists with local experience and knowledge of the culture, who are willing to serve as educators, policy advisors, and advocates, can make a difference. This is Part I of a two-part article. Part I reviews the burden of epilepsy and the current state of resources for treatment in developing countries, while Part II (to be published in Epilepsy Currents issue 10.5) will provide an "Overview of Care" in these countries.


The unstable bladder.
The unstable bladder is a common clinical problem of uncertain aetiology. Current in vitro studies of unstable human detrusor samples show differences in behaviour and response to pharmacological agents from normal detrusor. The fundamental urodynamic abnormality is the occurrence of involuntary detrusor contractions which cause the cardinal symptom of urgency. The incidence of other symptoms is determined by the functional bladder capacity and the patient's ability to resist the unstable contractions. Having excluded outflow obstruction as a causative or associated factor, empirical treatment may reasonably be started on the basis of the findings of a 48-hour voided volume chart, reserving full urodynamic investigation for patients who fail to respond to treatment as expected. For those with minimal urodynamic dysfunction, bladder drill is the treatment of choice; when this fails or is inappropriate, drug treatment with oxybutynin is indicated, supplemented by other drugs when appropriate. When these standard conservative measures fail, transvesical injection of the pelvic plexuses with phenol gives worthwhile results and is a trivial procedure. If this fails, and in men in whom the phenol procedure is contraindicated, 'clam' ileocystoplasty is usually if not always curative.


Prevalence of human papillomavirus genotypes and related abnormalities of cervical cytological results among HIV-1-infected women in Rochester, New York.
Women with human immunodeficiency virus (HIV) infection have higher rates of concurrent human papillomavirus (HPV) infection and cervical dysplasia than do HIV-uninfected women. They are also more commonly infected with multiple HPV types simultaneously. To determine the prevalence of different HPV genotypes in a group of HIV-infected women and to correlate these findings with cervical cytological results, we studied a group of 229 women attending a university-based HIV clinic during a 7-year period. When cervicovaginal lavage specimens, the reverse line-blot assay, and DNA sequencing were used, the most commonly detected HPV types (in decreasing order of frequency) were 56, 53, 16, 58, 52, MM7, MM8, and 33. These results contrast sharply with similar studies of HIV-uninfected women, in whom HPV-16 and -18 generally predominate. In our study, the HPV types most commonly associated with low-grade squamous intraepithelial lesions (SILs) were 56 and 53. Types most commonly associated with high-grade SILs were 52 and 58. High-risk HPV types other than 16 and 18 are often found in HIV-infected women and are frequently associated with abnormal cervical cytological results in this setting. These observations have implications for the design of future HPV vaccines.


Usefulness of Mitral Regurgitant Volume Quantified Using Magnetic Resonance Imaging to Predict Left Ventricular Remodeling After Mitral Valve "Correction".
MRI studies have shown a tight correlation between mitral regurgitant volume and left ventricular end-diastolic volume (LV EDV) in patients with primary chronic mitral regurgitation (MR). They have also shown a tight correlation between regurgitant volume and the decrease in LVEDV following mitral valve surgery. The purpose of this study is to validate an empiric calculation that can be used preoperatively to predict the amount of left ventricular remodeling following mitral valve correction. This is a prospective multicenter study of 63 (61 ± 13 years, male 65%) patients who underwent an MRI before and after mitral valve correction. Pre and postmitral valve correction ventricular volumes and ejection fractions were quantified. The predicted change in LV EDV was empirically calculated as mitral regurgitant volume/left ventricular ejection fraction. The observed change in LV EDV was compared to the predicted change in LV EDV. The LVEDV decreased in 61 (97%) patients following mitral valve correction (237 ± 66 ml vs 164 ± 46 ml, p <0.0001). Correlation between the observed and predicted change in LVEDV was good for the entire cohort (r = 0.77, p <0.0001) and excellent in patients with <10 ml of residual MR (r = 0.87, p <0.0001). This tight correlation was seen in both patients with primary (0.86, p <0.0001) and secondary MR (0.97, p <0.0001) and <10 ml of residual MR. Multivariate predictors of LV remodeling were MR volume, primary MR, and LVESV. In conclusion cardiac MRI volumetric measurements accurately predict LV remodeling following mitral valve correction. This finding supports the notion that MRI accurately quantifies the severity of chronic mitral regurgitation and a cardiac MRI should be strongly considered before mitral valve correction.


Problem oriented medical records: their impact on staff communication, attitudes and decision making.
A comparative, two-stage between hospital study involving university rehabilitation centers was undertaken to evaluate the impact of the problem oriented medical record (POMR) on staff communication, attitude change and decision making. Staff characteristics varied from one center to another. The semantic differential component of the project did not reveal any change due to the POMR in the staff perception of the medical record, the health care team or the various health professions. However, team function with respect to the management of specific patients improved in the centers which implemented the POMR during the time period of the project.


Respiration by "marine snow" at high hydrostatic pressure: Insights from continuous oxygen measurements in a rotating pressure tank.
It is generally anticipated that particulate organic carbon (POC) for most part is degraded by attached microorganisms during the descent of "marine snow" aggregates toward the deep sea. There is, however, increasing evidence that fresh aggregates can reach great depth and sustain relatively high biological activity in the deep sea. Using a novel high-pressure setup, we tested the hypothesis that increasing levels of hydrostatic pressure inhibit POC degradation in aggregates rapidly sinking to the ocean interior. Respiration activity, a proxy for POC degradation, was measured directly and continuously at up to 100 MPa (corresponding to 10 km water depth) in a rotating pressure tank that keeps the aggregates in a sinking mode. Model diatom-bacteria aggregates, cultures of the aggregate-forming diatom Skeletonema marinoi, and seawater microbial communities devoid of diatoms showed incomplete and complete inhibition of respiration activity when exposed to pressure levels of 10-50 and 60-100 MPa, respectively. This implies reduced POC degradation and hence enhanced POC export to hadal trenches through fast-sinking, pressure-exposed aggregates. Notably, continuous respiration measurements at ≥50 MPa revealed curved instead of linear oxygen time series whenever S. marinoi was present, which was not captured by discrete respiration measurements. These curvatures correspond to alternating phases of high and low respiration activity likely connected to pressure effects on unidentified metabolic processes in S. marinoi.


Extensive management promotes plant and microbial nitrogen retention in temperate grassland.
Leaching losses of nitrogen (N) from soil and atmospheric N deposition have led to widespread changes in plant community and microbial community composition, but our knowledge of the factors that determine ecosystem N retention is limited. A common feature of extensively managed, species-rich grasslands is that they have fungal-dominated microbial communities, which might reduce soil N losses and increase ecosystem N retention, which is pivotal for pollution mitigation and sustainable food production. However, the mechanisms that underpin improved N retention in extensively managed, species-rich grasslands are unclear. We combined a landscape-scale field study and glasshouse experiment to test how grassland management affects plant and soil N retention. Specifically, we hypothesised that extensively managed, species-rich grasslands of high conservation value would have lower N loss and greater N retention than intensively managed, species-poor grasslands, and that this would be due to a greater immobilisation of N by a more fungal-dominated microbial community. In the field study, we found that extensively managed, species-rich grasslands had lower N leaching losses. Soil inorganic N availability decreased with increasing abundance of fungi relative to bacteria, although the best predictor of soil N leaching was the C/N ratio of aboveground plant biomass. In the associated glasshouse experiment we found that retention of added (15)N was greater in extensively than in intensively managed grasslands, which was attributed to a combination of greater root uptake and microbial immobilisation of (15)N in the former, and that microbial immobilisation increased with increasing biomass and abundance of fungi. These findings show that grassland management affects mechanisms of N retention in soil through changes in root and microbial uptake of N. Moreover, they support the notion that microbial communities might be the key to improved N retention through tightening linkages between plants and microbes and reducing N availability.


Protein-DNA interactions in vivo of an erythroid-specific, human beta-globin locus enhancer.
The 5' DNase I-hypersensitive site 2 (5' HS-2) is an erythroid-specific enhancer located 11 kilobases (kb) upstream of the human beta-globin gene cluster. Presence in cis of 5' HS-2 confers a high level of erythroid cell-specific and developmentally regulated promoter activities of human globin genes in transfected cell cultures and in transgenic mice. Combining the use of the methylation protection assay and polymerase chain reaction, we have studied nuclear factor-DNA interactions of the 5' HS-2 enhancer in vitro and in vivo. The data from analyses of three different sequence motifs within 5' HS-2 represent three different modes of protein-DNA interaction with respect to cell-type specificities and in vivo vs. in vitro differences. First, a GATA-1 motif was found to bind nuclear factor(s), presumably the GATA-1 factor, present in K-562 cell extracts and in living K-562 cells. No such binding was seen in nonerythroid HeLa cells or extract. A second motif, NF-E2/AP1 (nuclear factor-erythroid 2/activator protein 1), consists of tandemly arranged dimers of AP1 binding consensus. The presence of either HeLa extract or K-562 extract protects the NF-E2/AP1 motif from methylation, but the footprints are different. This is most likely due to different protein-DNA contacts of the AP1-DNA complex formed in HeLa extract and the NF-E2-DNA complex in K-562 extract. In vivo methylation protection patterns of this motif parallel those observed in vitro, suggesting that it is also bound by NF-E2 in K-562 cells and by AP1 in HeLa cells. Finally, a GT-I motif binds apparently to one or more similar factors in both types of nuclear extracts, but the in vivo methylation protection patterns are not identical between living HeLa and K-562 cells. These data provide direct evidence that specific nuclear factor-DNA complexes form in vivo at functionally important sequence motifs of the 5' HS-2 enhancer in erythroid cells. The detection of conformationally different nuclear factor-DNA complexes at the same sequence motifs in HeLa and Raji cell lines also raises interesting questions regarding the origin and function of these complexes in nonerythroid cells.


Longitudinal [18F]FB-IL-2 PET Imaging to Assess the Immunopathogenicity of O'nyong-nyong Virus Infection.
O'nyong-nyong virus (ONNV) is an arthritogenic alphavirus that caused two large epidemics in 1959 and 1996, affecting millions of people in Africa. More recently, sero-surveillance of healthy blood donors conducted in 2019 revealed high rates of unreported ONNV infection in Uganda. Due to similar clinical symptoms with other endemic mosquito-borne pathogens in the region, including chikungunya virus, dengue virus and malaria, ONNV infections are often un- or misdiagnosed. Elucidating the immunopathogenic factors of this re-emerging arbovirus is critical with the expanding geographic distribution of competent vectors. This study reports the establishment of an immune competent C57BL6/J mouse model to mechanistically characterize ONNV infection and assess potential treatment efficacy. This mouse model successfully recapitulated arthralgia and viremia profiles seen in ONNV patients. Furthermore, longitudinal in-vivo PET imaging with [18F]FB-IL-2 (CD25+CD4+ binding probe) and histopathological assessment in this model demonstrated the pathogenic role of CD4+ T cells in driving joint pathology. Concordantly, in vivo CD4+ T cell depletion, or suppression with fingolimod, an FDA-approved immunomodulating drug, abrogated CD4+ T cell-mediated disease. This study demonstrates the importance of this immune competent ONNV model for future studies on factors influencing disease pathogenesis, which could shape the discovery of novel therapeutic strategies for arthritogenic alphaviruses.


Machine learning to predict rapid progression of carotid atherosclerosis in patients with impaired glucose tolerance.
Prediabetes is a major epidemic and is associated with adverse cardio-cerebrovascular outcomes. Early identification of patients who will develop rapid progression of atherosclerosis could be beneficial for improved risk stratification. In this paper, we investigate important factors impacting the prediction, using several machine learning methods, of rapid progression of carotid intima-media thickness in impaired glucose tolerance (IGT) participants. In the Actos Now for Prevention of Diabetes (ACT NOW) study, 382 participants with IGT underwent carotid intima-media thickness (CIMT) ultrasound evaluation at baseline and at 15-18 months, and were divided into rapid progressors (RP, n = 39, 58 ± 17.5 μM change) and non-rapid progressors (NRP, n = 343, 5.8 ± 20 μM change, p < 0.001 versus RP). To deal with complex multi-modal data consisting of demographic, clinical, and laboratory variables, we propose a general data-driven framework to investigate the ACT NOW dataset. In particular, we first employed a Fisher Score-based feature selection method to identify the most effective variables and then proposed a probabilistic Bayes-based learning method for the prediction. Comparison of the methods and factors was conducted using area under the receiver operating characteristic curve (AUC) analyses and Brier score. The experimental results show that the proposed learning methods performed well in identifying or predicting RP. Among the methods, the performance of Naïve Bayes was the best (AUC 0.797, Brier score 0.085) compared to multilayer perceptron (0.729, 0.086) and random forest (0.642, 0.10). The results also show that feature selection has a significant positive impact on the data prediction performance. By dealing with multi-modal data, the proposed learning methods show effectiveness in predicting prediabetics at risk for rapid atherosclerosis progression. The proposed framework demonstrated utility in outcome prediction in a typical multidimensional clinical dataset with a relatively small number of subjects, extending the potential utility of machine learning approaches beyond extremely large-scale datasets.


Effects of an early-life paraquat exposure on adult resistance to oxidative stress, plumage colour and sperm performance in a wild bird.
Early-life stressful conditions can shape individual phenotypes and ultimately influence fitness. Oxidative stress is a pervasive threat that affects many fitness-related traits and can modulate life-history trade-offs. Yet, the extent to which exposure to oxidative stress during early life can have long-lasting effects on key fitness-related traits remains to be elucidated, particularly in natural populations of vertebrates. Using a wild population of great tits Parus major, we experimentally dosed 11-day-old birds with paraquat, a pro-oxidant molecule, aiming at increasing oxidative stress. One year later, we recaptured 39 of them as adult recruiting breeders and quantified effects of the paraquat exposure on their resistance to oxidative stress, carotenoid-based plumage coloration and male sperm performance. Despite the absence of a short-term effect of paraquat on oxidative stress measured two days later, the pre-fledging exposure to paraquat induced a reduction in individual oxidative damage measured at adulthood. Paraquat-dosed individuals also had brighter plumage, but no effect was observed on male sperm performance. For the first time in a natural population of vertebrates, we experimentally show that an early-life acute exposure to a pro-oxidant has long-lasting effects on individual resistance to oxidative stress at adulthood. Our results are in line with the environmental matching and the hormesis hypotheses but may also reflect selective disappearance of individuals with lower resistance to oxidative stress.


Effect of Visual Information on Postural Control in Children with Autism Spectrum Disorder.
Visual information is crucial for postural control. Visual processing in children with autism spectrum disorder (ASD) was hypothesized to be less efficient and thus they would display a less stable standing posture than typically developing children. The present study compared the static standing responses and attentional demands of 15 children with ASD and 18 control participants in conditions of eyes open and eyes closed. The results showed that postural responses and attention invested in standing were similar between the participant groups in the two visual conditions. Both groups displayed a more stable posture when their eyes were open in comparison to eyes closed. The finding suggests that normal postural control development could occur in children with ASD.


How Could Future AI Help Tackle Global Complex Problems?
How does AI need to evolve in order to better support more effective decision-making in managing the many complex problems we face at every scale, from global climate change, collapsing ecosystems, international conflicts and extremism, through to all the dimensions of public policy, economics, and governance that affect human well-being? Research in complex decision-making at an individual human level (understanding of what constitutes more, and less, effective decision-making behaviors, and in particular the many pathways to failures in dealing with complex problems), informs a discussion about the potential for AI to aid in mitigating those failures and enabling a more robust and adaptive (and therefore more effective) decision-making framework, calling for AI to move well-beyond the current envelope of competencies.