Developmental plasticity links local adaptation and evolutionary diversification in foraging morphology.
Developmental plasticity is thought to reconcile the constraining role of natural selection in maintaining local adaptation with evolutionary diversification under novel conditions, but empirical documentations are rare. In vertebrates, growth and development of bones is partially guided by contractions of attached musculature and such muscle activity changes progressively through embryonic development from sporadic motility to direct functional effects. In species with short generation times, delayed skull maturation extends the guiding effects of muscle activity on formation of foraging morphology into adulthood, providing an opportunity to directly examine the links between plasticity of bone development, ecological adaptations, and evolutionary diversification in foraging morphology. In this case, the morphological consequences of inputs due to local functional requirements should be evident in adaptive divergence across taxa. Here we provide evidence that epigenetic regulation of bone growth in Soricid shrews may enable both development of local adaptations and evolutionary divergence in mandibular morphology. We contrast the effects of muscle stimulation on early- vs. late-maturing components of, foraging apparatus to show that the morphology of late-maturing components is more affected by functional requirements than are early-ossifying traits. Further, the divergence in foraging morphology across shrew species occurs along the directions delineated by inductive effects of muscle loading and bite force on bone formation in late-maturing but not early-maturing mandible components within species. These results support the hypothesis that developmental plasticity can link maintenance of local adaptations with evolutionary diversification in morphology.


Temperature variation and heat wave and cold spell impacts on years of life lost among the urban poor population of Nairobi, Kenya.
Weather extremes are associated with adverse health outcomes, including mortality. Studies have investigated the mortality risk of temperature in terms of excess mortality, however, this risk estimate may not be appealing to policy makers assessing the benefits expected for any interventions to be adopted. To provide further evidence of the burden of extreme temperatures, we analyzed the effect of temperature on years of life lost (YLL) due to all-cause mortality among the population in two urban informal settlements. YLL was generated based on the life expectancy of the population during the study period by applying a survival analysis approach. Association between daily maximum temperature and YLL was assessed using a distributed lag nonlinear model. In addition, cold spell and heat wave effects, as defined according to different percentiles, were investigated. The exposure-response curve between temperature and YLL was J-shaped, with the minimum mortality temperature (MMT) of 26 °C. An average temperature of 21 °C compared to the MMT was associated with an increase of 27.4 YLL per day (95% CI, 2.7-52.0 years). However, there was no additional effect for extended periods of cold spells, nor did we find significant associations between YLL to heat or heat waves. Overall, increased YLL from all-causes were associated with cold spells indicating the need for initiating measure for reducing health burdens.


Effects of diets high in refined carbohydrates on renal ammonium excretion in rats.
Ammonium excretion was investigated in spontaneously hypertensive rats (SHR) and normotensive control rats (WKY) ingesting different diets. SHR and WKY on low protein-high sucrose diets surprisingly showed the same ammonium excretion as rats ingesting a higher protein-lower sucrose diet. This was unexpected, because ammonium excretion correlates positively with protein intake. The relatively high ammonium excretion despite low protein intake (approximately 40% of control) was not associated with acidosis, hypokalemia, hypocalcemia, and/or hypomagnesemia. In a follow-up study, where diets were high in refined carbohydrates (sucrose, glucose, and starch) but more equal in protein content compared with a diet high in carbohydrates of a more complex form (grains), ammonium excretion increased significantly. When we examined the factors known to influence ammonium excretion, the only significant positive correlations found were between norepinephrine, epinephrine, dopamine, and ammonium excretion. These correlations still remained significant when only the data from the rats on the diets high in refined carbohydrates, i.e., rats on the same dietary intake of minerals and proteins, were compared. In vitro, we corroborated that catecholamines significantly increased ammoniagenesis from kidney slices. Our data show that diets high in refined carbohydrates augment both ammonium and catecholamine excretion and suggest that these two events may be interrelated.


Signal Modulation of Organic Photoelectrochemical Transistor by a Z-Scheme Photocathodic Gate: An Innovative Dual Amplification Strategy for Sensitive Aptasensing Application.
Pursuing a more efficient signal amplification strategy is highly demanded for improving the performance of the promising cathodic photoelectrochemical (PEC) sensors. In this work, we present an extremely effective dual signal amplification strategy by the integration of a Z-scheme nanohybrids-based photocathode with the effective signal modulation of an organic photoelectrochemical transistor (OPECT) device. Specifically, photocathodic gate material of CdTe-BiOBr nanohybrids with a Z-scheme electron-transfer route was designed and synthesized for preliminary improvement of the activity of the photogate; afterward, signal modulation of the OPECT system by the photocathodic gate of CdTe-BiOBr was then accomplished for further signal amplification by 2 orders of magnitude. As a result, the output PEC signal of CdTe-BiOBr was enhanced by 17.5-fold as compared to BiOBr, and the channel current (IDS) of the OPECT device was 117-fold magnified than its gate current (IG) response. Exemplified by tetracycline (TC) as a model target and aptamer as the specific recognition element, a versatile cathodic aptasensing platform was constructed based on the proposed OPECT device. The introduced OPECT aptasensor merits advantages, including a good linear range (1.0 × 10-12 to 1.0 × 10-6 M), a low limit of detection (4.2 × 10-13 M), and superior sensitivity than the traditional PEC methods for TC detection, which represents a universal protocol for developing the innovative photocathodic OPECT sensing platform toward accurate analysis.


Acoustic wave-based sensors using mode conversion in periodic gratings.
Using periodic gratings etched into the surface of a piezoelectric plate, surface acoustic waves (SAW) can be converted into bulk waves and vice versa with high efficiency. If parallel grating structures are fabricated on opposite surfaces of a piezoelectric plate, a SAW also can be directed from one surface to the other. Using such structures, acoustic wave-based sensors can be designed that utilize SAW for the detection of chemical analytes on an electrode-free surface, i.e., the back surface. As a result, spurious sensor response and electrode aging that may occur when a chemical analyte comes in contact with the transducers are minimized. The design principles of these grating-based SAW sensors are explained, and the mass sensitivity is investigated using chemical vapor deposited thin polymer films, a type of material used in many practical chemical sensor applications. Experimental results are presented for the detection of nitrogen dioxide (NO(2 )) in sub-ppm concentrations.


[Mechanism of action of lithium: intracellular signaling pathways].
Lithium is highly effective in the treatment of bipolar disorders and has multiple effects on embryonic development, glycogen synthesis, hematopoiesis and other biological processes. However, the mechanism of lithium action is still unclear. A variety of enzymes have been proposed as potential targets of lithium action, including inositol monophosphatase, a family of second messenger, and the protein kinase glycogen synthase kinase-3. This article proposes that multiple actions of lithium are critical for its therapeutic effects, and that these complex effects stabilize neuronal activities, support neural plasticity and provide neuroprotection.


Photodynamic therapy for multiple primary bronchogenic carcinoma.
In recent years, multiple primary lung cancers have been reported with greater frequency, partly as a result of technologic advances in the detection of lung cancer and therapeutic achievements in its management. Photodynamic therapy (PDT) is a relatively new therapy used with increasing frequency in the treatment of a wide variety of malignancies, including central lung cancers. In PDT, the differential retention of an injected photosensitizer by malignant tissue is exploited by treatment with a low-power laser beam delivered endoscopically. Since 1980, 145 patients with central lung cancers, including 35 cases of endoscopically evaluated early-stage lesions were treated with PDT at Tokyo Medical College. Thirteen of these 145 patients had multiple primary bronchogenic carcinomas, five cases of which were synchronous with the rest, metachronous. Three of 13 patients with multiple tumors had early-stage lesions and were treated with endoscopic PDT alone. In the other ten cases, PDT was used to treat accessible early-stage foci although operative excision was required for advanced lesions. Mean survival after PDT, alone or in combination with surgery, was 38 months (range, 14 to 87 months), and seven patients remain alive to date. It was concluded that PDT is useful in extending the therapeutic options for, and improving the prognosis of patients with, multiple primary bronchogenic carcinomas.


The Molecular Mechanism of Perillaldehyde Inducing Cell Death in Aspergillus flavus by Inhibiting Energy Metabolism Revealed by Transcriptome Sequencing.
Perillaldehyde (PAE), an essential oil in Perilla plants, serves as a safe flavor ingredient in foods, and shows an effectively antifungal activity. Reactive oxygen species (ROS) accumulation in Aspergillus flavus plays a critical role in initiating a metacaspase-dependent apoptosis. However, the reason for ROS accumulation in A. flavus is not yet clear. Using transcriptome sequencing of A. flavus treated with different concentrations of PAE, our data showed that the ROS accumulation might have been as a result of an inhibition of energy metabolism with less production of reducing power. By means of GO and KEGG enrichment analysis, we screened four key pathways, which were divided into two distinct groups: a downregulated group that was made up of the glycolysis and pentose phosphate pathway, and an upregulated group that consisted of MAPK signaling pathway and GSH metabolism pathway. The inhibition of dehydrogenase gene expression in two glycometabolism pathways might play a crucial role in antifungal mechanism of PAE. Also, in our present study, we systematically showed a gene interaction network of how genes of four subsets are effected by PAE stress on glycometabolism, oxidant damage repair, and cell cycle control. This research may contribute to explaining an intrinsic antifungal mechanism of PAE against A. flavus.


Prevalence of islet cell antibodies and B cell functional status in insulin dependent diabetes.
As autoimmunity is an important factor in the etiopathogenesis of IDDM, 85 ketosis prone i.e. insulin dependent diabetes (IDD) were evaluated for immunological and beta cell functional status. Islet cell antibodies (ICA) against purified islet cells used in Microwell ELISA Method, were detected in 27.1% of cases (23/85). There was a prevalence of 36.4% of ICA positivity in newly diagnosed cases and its prevalence declined with duration. The highest ICA positivity was observed in fourth decade of life. 17 of the 23 ICA positive cases (73.9%) had a mean duration of 2.1 years whereas the remaining 6/23 (26.1%) had a mean duration of 9 years. Females showed a younger age of onset of diabetes. Only one female with duration of 10 years tested positive for ICA.ICA positive males had later age of onset and longer duration of diabetes as compared to ICA positive females. Ten ICA positive cases studied were showing non-significant C-peptide (CP) release (after glucose load) in comparison to negative cases (14); p < 0.05, 8 of these cases were with < 3 months duration. Significantly low delta % C-peptide response implies a low residual beta-cell function and further loss of beta cell function earlier in ICA +ve cases. Thus this study leads to understand in depth the immune mechanism of IDDM.


Applicability of the quantification of genetically modified organisms to foods processed from maize and soy.
The applicability of quantifying genetically modified (GM) maize and soy to processed foods was investigated using heat treatment processing models. The detection methods were based on real-time quantitative polymerase chain reaction (PCR) analysis. Ground seeds of insect resistant GM maize (MON810) and glyphosate tolerant Roundup Ready (RR) soy were dissolved in water and were heat treated by autoclaving for various time intervals. The calculated copy numbers of the recombinant and taxon specific deoxyribonucleic acid (DNA) sequences in the extracted DNA solution were found to decrease with time. This decrease was influenced by the PCR-amplified size. The conversion factor (Cf), which is the ratio of the recombinant DNA sequence to the taxon specific DNA sequence and is used as a constant number for calculating GM% at each event, tended to be stable when the sizes of PCR products of two DNA sequences were nearly equal. The results suggested that the size of the PCR product plays a key role in the quantification of GM organisms in processed foods. It is believed that the Cf of the endosperm (3n) is influenced by whether the GM originated from a paternal or maternal source. The embryos and endosperms were separated from the F1 generation seeds of five GM maize events, and their Cf values were measured. Both paternal and maternal GM events were identified. In these, the endosperm Cf was lower than that of the embryo, and the embryo Cf was lower than that of the endosperm. These results demonstrate the difficulties encountered in the determination of GM% in maize grains (F2 generation) and in processed foods from maize and soy.


N6-methyladenosine modification of OIP5-AS1 promotes glycolysis, tumorigenesis, and metastasis of gastric cancer by inhibiting Trim21-mediated hnRNPA1 ubiquitination and degradation.
Opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) has been demonstrated to play vital roles in development and progression of tumors such as gastric cancer (GC). However, the detailed molecular mechanism of OIP5-AS1 has not been completely elucidated. Our study aimed to investigate the role and the epigenetic regulation mechanism of OIP5-AS1 in GC. OIP5-AS1 expression in GC tissues was detected by RT-qPCR. Loss- and gain-of-function experiments were conducted to assess the biological function of OIP5-AS1 in vitro and in vivo. The interaction of OIP5-AS1 with insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) or heterogeneous nuclear nucleoprotein A1 (hnRNPA1) was verified by bioinformatics analysis, RNA pull-down assays, and RNA immunoprecipitation assays. In this study, we identified that OIP5-AS1 is specifically overexpressed in GC tumor tissues and cell lines and correlated with a poor prognosis. The loss of OIP5-AS1 suppressed the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and glycolysis of GC cells, but the ectopic expression of OIP5-AS1 had the opposite impact. Meanwhile, knockdown of OIP5-AS1 inhibited tumor growth in patient-derived xenograft models, as well as repressed tumor metastasis. Mechanistically, IGF2BP3 could bind to OIP5-AS1 by N6-methyladenosine (m6A) modification sites on OIP5-AS1, thereby stabilizing OIP5-AS1. Moreover, OIP5-AS1 prevented Trim21-mediated ubiquitination and degradation of hnRNPA1, stabilizing hnRNPA1 protein and promoting the malignant progression of GC by regulating PKM2 signaling pathway. In conclusion, this study highlighted that OIP5-AS1 is an oncogenic m6A-modified long non-coding RNA (lncRNA) in GC and that IGF2BP3/OIP5-AS1/hnRNPA1 axis may provide a potential diagnostic or prognostic target for GC.


An electronic voting scheme based on homomorphic encryption and decentralization.
Compared with paper-based voting, electronic voting not only has advantages in storage and transmission, but also can solve the security problems that exist in traditional voting. However, in practice, most electronic voting faces the risk of voting failure due to malicious voting by voters or ballot tampering by attackers. To solve this problem, this article proposes an electronic voting scheme based on homomorphic encryption and decentralization, which uses the Paillier homomorphic encryption method to ensure that the voting results are not leaked until the election is over. In addition, the scheme applies signatures and two layers of encryption to the ballots. First, the ballot is homomorphically encrypted using the homomorphic public key; then, the voter uses the private key to sign the ballot; and finally, the ballot is encrypted using the public key of the counting center. By signing the ballots and encrypting them in two layers, the security of the ballots in the transmission process and the establishment of the decentralized scheme are guaranteed. The security analysis shows that the proposed scheme can guarantee the completeness, verifiability, anonymity, and uniqueness of the electronic voting scheme. The performance analysis shows that the computational efficiency of the proposed scheme is improved by about 66.7% compared with the Fan et al. scheme (https://doi.org/10.1016/j.future.2019.10.016).


So Useful as a Good Theory? The Practicality Crisis in (Social) Psychological Theory.
Practicality was a valued attribute of academic psychological theory during its initial decades, but usefulness has since faded in importance to the field. Theories are now evaluated mainly on their ability to account for decontextualized laboratory data and not their ability to help solve societal problems. With laudable exceptions in the clinical, intergroup, and health domains, most psychological theories have little relevance to people's everyday lives, poor accessibility to policymakers, or even applicability to the work of other academics who are better positioned to translate the theories to the practical realm. We refer to the lack of relevance, accessibility, and applicability of psychological theory to the rest of society as the practicality crisis. The practicality crisis harms the field in its ability to attract the next generation of scholars and maintain viability at the national level. We describe practical theory and illustrate its use in the field of self-regulation. Psychological theory is historically and scientifically well positioned to become useful should scholars in the field decide to value practicality. We offer a set of incentives to encourage the return of social psychology to the Lewinian vision of a useful science that speaks to pressing social issues.


Fractionated stereotactic radiosurgery treatment results for skull base chordomas.
Chordomas are uncommon neoplasms and there is still controversy regarding establishment of diagnosis and management. The aim of this study was to evaluate efficacy and toxicity of fractionated stereotactic radiosurgery (FSRS) in skull base chordomas. There were 4 female (36%) and 7 male (64%) patients. FSRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). The median tumor volume was 14.7 cc (range, 3.9-40.5 cc). The median marginal tumor dose was 30 Gy (range, 20-36 Gy) in a median 5 fractions (range, 3-5 fractions). The median follow-up time was 42 months (range, 17-63 months). At the time of analysis, 10 (91%) patients were alive and 1 (9%) had died due to tumor progression. Of 10 patients, 8 (73%) had stable disease and the remaining 2 (18%) had progressive disease. The actuarial overall survival (OS) after FSRS was 91% at two-years. Two patients developed radiation-induced brain necrosis as a complication in the 8th and 28th months of follow-up, respectively. Our results with robotic FSRS in skull base chordomas are promising for selected patients. However, due to the slow growth pattern of skull base chordomas, a longer follow-up is required to determine exact treatment results and late morbidity.


Neuronal gating of tactile input and sleep in 10-month-old infants at typical and elevated likelihood for autism spectrum disorder.
Sleep problems in Autism Spectrum Disorder (ASD) emerge early in development, yet the origin remains unclear. Here, we characterise developmental trajectories in sleep onset latency (SOL) and night awakenings in infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) and infants at typical likelihood (TL) for ASD. Further, we test whether the ability to gate tactile input, using an EEG tactile suppression index (TSI), associates with variation in SOL and night awakenings. Parent-reported night awakenings and SOL from 124 infants (97 at EL for ASD) at 5, 10 and 14 months were analyzed using generalized estimating equations. Compared to TL infants, infants at EL had significantly more awakenings and longer SOL at 10 and 14 months. The TSI predicted SOL concurrently at 10 months, independent of ASD likelihood status, but not longitudinally at 14 months. The TSI did not predict night awakenings concurrently or longitudinally. These results imply that infants at EL for ASD wake up more frequently during the night and take longer to fall asleep from 10 months of age. At 10 months, sensory gating predicts SOL, but not night awakenings, suggesting sensory gating differentially affects neural mechanisms of sleep initiation and maintenance.


Hyperbaric therapy provides no benefit for skeletal muscle and respiratory function and accelerates cardiac injury in mdx mice.
Duchenne muscular dystrophy (DMD) is a uniformly fatal condition of striated muscle wasting resulting in premature death from respiratory and/or cardiac failure. Symptomatic therapy has prolonged survival by limiting deaths resulting from respiratory insufficiency, but there is currently no effective therapy for most patients with DMD. This grim prognosis has led patients and their families to seek unproven therapeutic approaches. One such approach is the use of hyperbaric therapies, which 14% of DMD patients self-report using. The primary goal of this study was to determine if intermittent hyperbaric exposure altered the muscle function of the mdx mouse, a genetic model of DMD. To do this, mdx mice were exposed to three daily 90-minute 1.3 atmosphere hyperbaric exposures for 4 weeks. Skeletal muscle, respiratory, and cardiac function were assessed in treated and untreated wild type and dystrophic mice. The results of these studies find that hyperbaric and hyperoxic approaches resulted in increased cardiac fibrosis in dystrophic mice and no beneficial effects on the functional parameters measured. These data suggest that these oxygen-based therapies are unlikely to provide therapeutic benefit to DMD patients.


Control of pet animals.
Pet animals play an important and valuable role in human society, but irresponsible ownership has created problems of surplus animals, threats to health, pollution, nuisance, cruelty and neglect. Urgent and drastic action is required to deal with the situation, and the measures proposed include the appointment of dog wardens, limitation of numbers, enclosure and leash laws, and subsidised spay clinics.


Linking large administrative databases: a method for conducting emergency medical services cohort studies using existing data.
To evaluate probabilistic matching for linking a cohort of cardiac arrest (CA) patients identified in the Metro Toronto Ambulance (MTA) database in Toronto, Ontario, Canada, to their appropriate record in either the Vital Statistics Information System (VSIS) or the Canadian Institute of Health Information (CIHI) databases and thus establish their clinical outcomes. A linkage of a large administrative database was performed. A cohort of patients who suffered an out-of-hospital CA during the calendar years 1988-1993 was identified. To determine the patients' outcomes, the cohort was probabilistically linked to patient records in the VSIS and CIHI databases. Identifying variables used during the process of linking records included: names (first and last); New York State Identification and Intelligence System (NYSIIS) code; date of event; date of death; city; admitting hospital number; mode of admission to hospital; age; and sex. A cohort of 7,079 CA patients was identified from the MTA database; 6,448 (91%) patients were accurately linked to records in 1 of the 2 outcome databases (CIHI, VSIS). Missing data for > or = 1 of the linking variables were responsible for unlinked records. Using these longitudinal data, it was possible to determine the number of patients surviving their out-of-hospital CAs to be admitted to hospital (n = 833) (16%). No differences in survival rates (p = 0.06) or median lengths of hospital stay among the survivors (p = 0.15) were observed between admitting hospitals. Probabilistic matching is an effective method by which researchers can use existing administrative data to determine outcomes of population cohorts. This is especially valuable in situations where controlled intervention studies are not feasible or may be inappropriate. In this analysis, in-hospital management of admitted CA patients, as determined by hospital-specific survival rates and length of stay, suggests no measurable differences in the care provided to these patients by hospitals in Toronto.


Entecavir therapy combined with DNA vaccination for persistent duck hepatitis B virus infection.
This study was designed to test the efficacy of antiviral treatment with entecavir (ETV) in combination with DNA vaccines expressing duck hepatitis B virus (DHBV) antigens as a therapy for persistent DHBV infection in ducks. Ducks were inoculated with 10(9) DHBV genomes at 7 days of age, leading to widespread infection of the liver and viremia within 7 days, and were then treated orally with either ETV (0.1 mg/kg of body weight/day) or distilled water from 21 days posthatch for 244 days. Treatment with ETV caused a 4-log drop in serum DHBV DNA levels within 80 days and a slower 2- to 3-log drop in serum DHBV surface antigen (DHBsAg) levels within 120 days. Following withdrawal of ETV, levels of serum DHBV DNA and DHBsAg rebounded to match those in the water-treated animals within 40 days. Sequential liver biopsy samples collected throughout the study showed that ETV treatment reduced DHBV DNA replicative intermediates 70-fold in the liver, while the level of the stable, template form, covalently closed circular DNA decreased only 4-fold. ETV treatment reduced both the intensity of antigen staining and the percentage of antigen-positive hepatocytes in the liver, but the intensity of antigen staining in bile duct cells appeared not to be effected. Intramuscular administration of five doses of a DNA vaccine expressing the DHBV presurface, surface, precore, and core antigens, both alone and concurrently with ETV treatment, on days 50, 64, 78, 127, and 141 did not result in any significant effect on viral markers.


Design and development of human resource management computer system for enterprise employees.
Client-Server (C/S) application is always used in the existing Human Resource Management System (HRMS) as the system architecture, which has the problems of complex maintenance and poor compatibility; and cannot use professional database and development system, making the system development difficult and the data security low. To solve the above problems, the overall demand is analyzed, as well as feasibility and key technologies of the enterprise HRMS system. Then a HRMS is designed and developed, based on the user's key functional requirements and related technologies, which is reasonable and easy to maintain. The system is supported by Browser-Server (B/S) structure, with the current popular Java 2 Platform Enterprise Edition (J2EE) multi-level structure as the overall architecture. The mature Microsoft SQL Server 2008 introduced by Microsoft is used as the database platform. Combined with Model View Controller (MVC) design pattern, this system can be used by users without geographical restrictions and system maintenance. In this system, performance logic and business logic are separated, which makes it convenient for the development and maintenance of the system. The system mainly includes six modules: personnel management, organizational management, recruitment management, training management, salary management and system management, which integrates enterprise information and realizes the functions of easy access and easy query of information database. Its interface is simple, easy to understand, and easy to operate, with low investment, low cost, high safety, good performance and easy maintenance, which help to improve the work efficiency and modern management level of enterprises. In the end, the operation performance of the system is tested. The results show that the throughput of the main functional modules in the system is greater than 100 times/s when dealing with the business, and the success rate of event processing is greater than 99%. The average response time of the business end is less than 0.4 s, and the average response time of the terminal side is less than 0.5 s, which all meet the standards. System CPU occupancy rate can be basically controlled below 30%, and memory usage rate is below 30%. In summary, the system designed here has the basic functions but also to ensure good performance, suitable for enterprise personnel management, organizational management, recruitment management, training management and salary management. The design and development of this system aims to provide technical support for the service quality of enterprise human resource management business, to improve the overall efficiency, promote the pace of enterprise strategic development, and enhance the market competitiveness of enterprises.


A Comprehensive Digital Program for Smoking Cessation: Assessing Feasibility in a Single-Group Cohort Study.
Cigarette smoking remains the leading cause of preventable death and disease worldwide. Evidence-based approaches are available, but few people access them. Although digital solutions offer great promise for population reach, few multicomponent programs exist. Pivot is a comprehensive digital solution combining a Food and Drug Administration-cleared carbon monoxide (CO) breath sensor; cigarette logging; a 6-phase, app-delivered smoking cessation program based on the US Clinical Practice Guidelines; and dedicated human coaching via text-based chat. The purpose of this study was to assess program engagement, changes in attitudes toward smoking, self-reported changes in smoking behavior, and program acceptability for the initial phase of Pivot: Explore. A total of 48 participants enrolled, and 41 completed the study. About half the participants (54%, 22/41) were men, and the mean age was 43 years. Most (85%, 35/41) were daily smokers and smoked an average of 12 cigarettes per day. Explore includes CO breath sensing, logging cigarettes in-app, learning via in-app activities, and dedicated human coaching through a text messaging interface. Participants completed surveys at baseline and exit assessing attitudes toward quitting including readiness, perceived difficulty, and confidence in quit success. At exit, participants also completed a survey of changes in smoking behavior and ratings of program acceptability. More than 80% of participants (34-39 of 41) took ≥1 CO breath sample each day, and more than 55% (23-27 of 41) took ≥5 samples each day. More than 65% of participants (27-34 of 41) logged ≥1 cigarette using the in-app logging feature each day. All 9 in-app activities had completion rates ≥80% (33-40 of 41). Response to coach-initiated outreach was also high, with all contacts receiving ≥73% (30-39 of 41) response. In matched pair analyses, significant positive changes in mean attitudes toward quitting (scale 1-10) were evident from baseline (T1) to study exit (T2), including increased readiness to quit (T1 mean=6.1, T2 mean=7.4, P=.005), lower perceived difficulty (T1 mean=3.7, T2 mean=5.6, P=.001), and greater expectations of success (T1 mean=4.5, T2 mean=6.5, P<.001). At exit, 78% (32/41) of participants reported decreasing the number of cigarettes smoked per day during the study. Participants rated program quality and satisfaction very high (mean ≥8 for all items). These results support the feasibility and acceptability of the initial 9-day phase of Pivot: Explore. Participants had high levels of engagement with sensing, logging, learning, and coaching. Attitudes toward quitting improved significantly, and the majority of users indicated decreasing smoking behavior. Explore was designed to raise smoker awareness and motivation. Additional research is underway to assess how users progress through the full Pivot smoking cessation program and determine the program's effectiveness for achieving sustained cessation.


Implantation failures in women with infertility associated endometriosis.
Endometriosis is currently considered as one of the most common diseases associated with infertility. A controversial issue is whether endometriosis per se exerts a detrimental effect on IVF outcomes. Failure of implantation due to endometriosis-associated infertility is a contradictory and widely discussed burden nowadays. The purpose of the study is to assess the quality of embryos and implantation rate in women with infertility associated with endometriosis. The study included infertile reproductive aged women, between 26 and 40 years who underwent IVF and ICSI procedures. The patients were divided into two groups: group I (n = 70) involved 70 patients with recurrent unilateral endometriomas, II control group (n = 50) with tubal factor infertility. The quality of the retrieved embryos was assessed according to the generally accepted classification of Gardner, indicating the rate of implantation in each group. Embryo transfer was performed in case of high quality embryos. Assessing the ovarian reserve indicators, in the group I patients with recurrent unilateral endometriomas the serum level of AMH was significantly lower (2.1 ± 1.75 vs. 3.2 ± 1.4, p < .005), as well as the number of retrieved oocytes (8.1 ± 3.9 and 10.1 ± 6.8, p < .005). The analysis of the results demonstrated that the duration of stimulation in the group patients with recurrent unilateral endometriomas was significantly higher in comparison with the group II (12.2 ± 1.8 and 10.2 ± 1.6 days, p < .001). Nevertheless, the number of good quality embryos retrieved was comparable in both groups (2.2 ± 1.5 and 2.8 ± 1.8). In the group I patients with recurrent unilateral endometriomas, there was a statistically significant decrease of implantation rate (17.1% vs. 24% p < .005). The results of the study revealed no statistical difference in embryo quality in the study cohort. However, it is important to note that a statistically significant difference in implantation rate in the group of endometriosis-associated infertility compared was obtained 1.5 times lower than in the control group (15.8% vs. 24.0% p < .005). The achieved results demonstrated an adverse IVF outcome in infertile women with recurrent endometrioma compared to the control group.


Using Simulation Modeling to Inform Policy Makers for Planning Physician Workforce in Healthcare System in Croatia.
The objective of this paper is to show how a simple but powerful simulation model can be build up using standard spreadsheet program and used to simulate future, needs and supply of physicians in order to inform policy makers at national level when deciding on enrollment to medical schools and immigration quotas for physicians. The Republic of Croatia is facing a serious shortage of physicians in the healthcare system and simulation results have shown that the gap between needs and supply will even increase if current enrollment qoutas to medical schools would persist. Increasing enrollment quotas, adjusting immigration policy, re-directing physicians from other professions to the healthcare system, task shift and skill mix options are just some of the measures needed to be taken promptly in order to prevent a huge deficit of physicians in the future. Simulation modeling is certainly a method for predicting changes within healthcare systems with a possibility to examine multiple different scenarios and suggest interventions.


From symptoms to leg edema: efficacy of Daflon 500 mg.
This article reviews the mechanisms by which micronized purified flavonoid fraction (MPFF; Daflon 500 mg) acts on symptoms as well as on edema in patients with chronic venous disease, in the light of new advances in the understanding of the pathophysiology of this chronic condition. Deterioration of venous wall tone followed by valve dysfunction leading eventually to varicose veins are the key pathophysiologic features that produce venous hypertension. Both mechanical and biological factors are responsible for the deterioration of the venous wall in large veins. These are decreased shear stress and hypoxia of the media and of the endothelium, which act as triggering factors for biochemical reactions leading to inflammation. There is a body of evidence that inflammation in chronic venous insufficiency (CVI) plays a role right from the early stages of venous dysfunction and venous valve restructuring. The whole process of venous wall stretching and dilation is painful and may present as leg heaviness, a sensation of swelling, and paresthesia. Daflon 500 mg relieves symptoms, edema, and red blood cell aggregation, which cause paresthesia and restless legs. At the level of the microcirculation, dysfunction of microvessels is observed, characterized by an increase in capillary permeability followed by skin changes. The earliest manifestation of microcirculatory disorder is edema. At this level, Daflon 500 mg acts favorably on microcirculatory complications by normalizing the synthesis of prostaglandins and free radicals. It decreases bradykinin-induced microvascular leakage and inhibits leukocyte activation, trapping, and migration. Its efficacy in decreasing CVI edema and ankle swelling has been proven in rigorous studies that are reviewed in this paper. Daflon 500 mg, a well-established oral flavonoid that consists of 90% micronized diosmin and 10% flavonoids expressed as hesperidin, may be prescribed from the very beginning of the disease for the relief of pain and edema, and in any CVI patient presenting with symptoms as well. Daflon 500 mg is thus the first-line treatment for edema and symptoms of CVI at any stage of the disease. At advanced disease stages, Daflon 500 mg may be used in conjunction with sclerotherapy, surgery, and/or compression therapy or as an alternative treatment when other treatments are not indicated or not feasible.


Pattern of Surgical Emergencies in Rural Southwestern Nigeria.
Considering the magnitude of deaths prevailing in the accident and emergency department (AED) in health facilities of sub-Sahara Africa, there is a need to have information on the burden of admissions and deaths due to surgical emergencies. Few studies in Nigerian hospitals in urban and suburban areas have been documented, but none in the rural setting. The objectives of this study were to ascertain the sociodemographic profile, causes and outcomes of admissions, and the pattern and causes of deaths due to surgical emergencies. A retrospective survey using a data form and a predetermined questionnaire was used to review the patients admitted for surgical emergencies at the AED of a tertiary hospital in rural southwestern Nigeria from January 2015 to December 2019. The data were analyzed using SPSS version 22.0. The results were presented in descriptive and tabular formats. Surgical emergencies constituted 43.9% of all admissions. The mean age of admissions was 42 ± 16.9 years, and majorities were in the young and middle-aged groups. There were more males (66.4%) than females (33.6%). Trauma(60.9%) of which road traffic accident (RTAs)(56.0%), was the leading mechanism of trauma. The mortality rate was 5.4% and was caused majorly by RTAs (33.0%), diabetes mellitus foot ulcers (11.0%), and malignancies (9.8%). In this study, surgical emergencies constituted 43.9%, and a majority of the patients were male. Trauma caused by RTA is the most cause of admission. The mortality rate was 5.4%. This finding may provide an impetus for prospective research on this outcome.


SERIES: eHealth in primary care. Part 5: A critical appraisal of five widely used eHealth applications for primary care - opportunities and challenges.
Given the pressure on modern healthcare systems, eHealth can offer valuable opportunities. However, understanding the potential and challenges of eHealth in daily practice can be challenging for many general practitioners (GPs) and their staff. To critically appraise five widely used eHealth applications, in relation to safe, evidence-based and high-quality eHealth. Using these applications as examples, we aim to increase understanding of eHealth among GPs and highlight the opportunities and challenges presented by eHealth. eHealth applications can support patients while increasing efficiency for GPs. A three-way division (inform, monitor, track; interaction; data utilisation) characterises many eHealth applications, with an increasing degree of complexity depending on the domain. All applications provide information and some have extra functionalities that promote interaction, while data analysis and artificial intelligence may be applied to support or (fully) automate care processes. Applications in the inform domain are relatively easy to use and implement but their impact on clinical outcomes may be limited. More demanding applications, in terms of privacy and ethical aspects, are found in the data utilisation domain and may potentially have a more significant impact on care processes and patient outcomes. When selecting and implementing eHealth applications, we recommend that GPs remain critical regarding preconditions on safe, evidence-based and high-quality eHealth, particularly in the case of more complex applications in the data utilisation domain.


Risk analysis and risk management.
During the past several decades, the public has given increasing attention to environmental problems and increased their demands that these problems be solved. During this period, the difficulty and costs of solving the problems have become apparent. Environmental abatement programs must be effective in achieving the desired goals and efficient in achieving them at low cost. Risk analysis is necessary to quantify the benefits of proposed solutions in order to make them effective and efficient. The necessity for performing risk assessment stems from a presidential executive order, from a Supreme Court Decision, and from the public's demand for information about the extent of possible danger from a hazard, rather than knowing simply that it is a hazard. The science of risk analysis is an an early stage and so there are many uncertainties concerning interpretation of the estimates. This approach has sharpened the scientific questions and hastened improvements in scientific understanding. Risk analysis is most helpful when the analysis reflects the science, without intrusion of the risk assessor's values or attempts to force a risk management outcome by skewing the risk analysis.


Selective immunoneutralization of luteinizing hormone results in the apoptotic cell death of pachytene spermatocytes and spermatids in the rat testis.
The selective withdrawal of pituitary gonadotropins through specific antibodies is known to cause disruption of spermatogenesis. The cellular mechanism responsible for the degenerative changes under isolated effect of luteinizing hormone (LH) deprivation is not clear. Using antibodies specific to LH we have investigated the effect of immunoneutralization of LH on apoptotic cell death in the testicular cells of the immature and the adult rats. Specific neutralization of LH resulted in apoptotic cell death of germ cells, both in the immature and the adult rats. The germ cells from control animals showed predominantly high molecular weight DNA, while the antiserum treated group showed DNA cleavage into low molecular weight DNA ladder characteristic of apoptosis. This pattern could be observed within 24 h of a/s administration and the effect could be reversed by testosterone. The germ cells were purified by centrifugal elutriation and the vulnerability of germ cell types to undergo apoptosis under LH deprivation was investigated. The round spermatids and the pachytene spermatocytes were found to be the most sensitive germ cells to lack of LH and underwent apoptosis. Interestingly, spermatogonial cells were found to be the least sensitive germ cells to the lack of LH in terms of apoptotic cell death. Results show that LH, in addition to being involved in the germ cell differentiation, is also involved in cell survival and prevent degeneration of germ cells during spermatogenesis. Apoptotic DNA fragmentation may serve as a useful marker for the study of hormonal regulation of spermatogenesis and the specific neutralization of gonadotropic hormones can be a reliable model for the study of the molecular mechanism of apoptosis.


Platelet satellitism as presenting finding in mantle cell lymphoma. A case report.
Platelet satellitism surrounding polymorphonuclear neutrophils has been observed almost exclusively in EDTA-treated blood at room temperature. The mechanism underlying this phenomenon is not understood fully. We report a case of platelet rosetting around atypical lymphocytes in peripheral blood smears made from EDTA-treated and untreated blood. Flow cytometry of the peripheral blood sample and immunohistochemical stains of the subsequent bone marrow biopsy specimen revealed a monoclonal B-cell population positive for CD5, CD20, and cyclin D1 and negative for CD3 and CD23; cytogenetic findings revealed a complex karyotype that included t(11;14). These findings were consistent with mantle cell lymphoma. To our knowledge, the finding of platelet satellitism involving mantle cell lymphoma cells in peripheral blood has not been reported previously.


Intravenous lidocaine as a non-opioid adjunct analgesic for traumatic rib fractures.
Pain management is the pillar of caring for patients with traumatic rib fractures. Intravenous lidocaine (IVL) is a well-established non-opioid analgesic for post-operative pain, yet its efficacy has yet to be investigated in trauma patients. We hypothesized that IVL is associated with decreased inpatient opioid requirements among patients with rib fractures. We retrospectively evaluated adult patients presenting to our Level 1 trauma center with isolated chest wall injuries. After 1:1 propensity score matching patients who received vs did not receive IVL, we compared the two groups' average daily opioid use, opioid use in the last 24 hours of admission, and pain scores during admissions hours 24-48. We performed multivariable linear regression for these outcomes (with sensitivity analysis for the opioid use outcomes), adjusting for age as a moderating factor and controlling for hospital length of stay and injury severity. We identified 534 patients, among whom 226 received IVL. Those who received IVL were older and had more serious injury. Compared to propensity-score matched patients who did not receive IVL, patients who received IVL had similar average daily opioid use and pain scores, but 40% lower opioid use during the last 24 hours of admission (p = 0.002). Multivariable regression-with and without sensitivity analysis-did not show an effect of IVL on any outcomes. IVL was crudely associated with decreased opioid requirements in the last 24 hours of admission, the time period associated with opioid use at 90 days post-discharge. However, we did not observe beneficial effects of IVL on multivariable adjusted analyses; we are conducting a randomized control trial to further evaluate IVL's opioid-sparing effects for patients with rib fractures.


Co-Optimization Free Lunches: Tractability of Optimal Black-Box Algorithms for Maximizing Expected Utility.
Co-optimization problems often involve settings in which the quality ( utility) of a potential solution is dependent on the scenario within which it is evaluated, and many such scenarios exist. Maximizing expected utility is simply the goal of finding the potential solution whose expected utility value over all possible scenarios is best. Such problems are often approached using coevolutionary algorithms. We are interested in the design of generally well-performing black-box algorithms for this problem, that is, algorithms which have access to the utility function only via input-output queries. We research this matter by focusing on three main questions: 1) are some algorithms strictly better than others when judged in aggregation over all possible instances of the problem? that is, is there "free lunch"? 2) do optimal algorithms exist? and 3) if so, do they have a tractable implementation? For a specific expected-utility maximization context, involving several assumptions and performance choices, we answer all three questions affirmatively and concretely: we provide examples of free lunch; we describe the general operation of optimal algorithms; we characterize situations when this operation has a very simple and efficient implementation, situations when the computational cost can be significantly reduced, and situations when tractability of optimal algorithms might be out of reach.


Automatic Diagnosis of Mild Cognitive Impairment Using Electroencephalogram Spectral Features.
Alzheimer's disease (AD) is one of the most expensive and fatal diseases in the elderly population. Up to now, no cure have been found for AD, so early stage diagnosis is the only way to control it. Mild cognitive impairment (MCI) usually is the early stage of AD which is defined as decreasing in mental abilities such a cognition, memory, and speech not too severe to interfere daily activities. MCI diagnosis is rather hard and usually assumed as normal consequences of aging. This study proposes an accurate, mobile, and nonexpensive diagnostic approach based on electroencephalogram (EEG) signal. EEG signals were recorded using 19 electrodes positioned according to the 10-20 International system at resting eyes closed state from 16 normal and 11 MCI participants. Nineteen Spectral features are computed for each channel and examined using a correlation based algorithm to select the best discriminative features. Selected features are classified using a combination of neurofuzzy system and k-nearest neighbor classifier. Final results reach 88.89%, 100%, and 83.33% for accuracy, sensitivity, and specificity, respectively, which shows the potential of proposed method to be used as an MCI diagnostic tool, especially for screening a large population.


Effectiveness of interventions promoting HIV serostatus disclosure to sexual partners: a systematic review.
Disclosure of HIV serostatus to sexual partners is mandated within certain states in the United States and other countries. Despite these laws implemented and public health efforts to increase disclosure, rates of disclosure to sexual partners among people living with HIV (PLWH) remain low, suggesting the need for interventions to assist PLWH with the disclosure process. We conducted a systematic review of studies testing whether HIV serostatus disclosure interventions increase disclosure to sexual partners. We searched six electronic databases and screened 484 records. Five studies published between 2005 and 2012 met inclusion criteria and were included in this review. Results showed that three of the HIV serostatus disclosure-related intervention studies were efficacious in promoting disclosure to sexual partners. Although all three studies were conducted in the United States the intervention content and measurements of disclosure across the studies varied, so broad conclusions are not possible. The findings suggest that more rigorous HIV serostatus disclosure-related intervention trials targeting different populations in the United States and abroad are needed to facilitate disclosure to sexual partners.


Phosphodiesterase-10A Inverse Changes in Striatopallidal and Striatoentopeduncular Pathways of a Transgenic Mouse Model of DYT1 Dystonia.
We report that changes of phosphodiesterase-10A (PDE10A) can map widespread functional imbalance of basal ganglia circuits in a mouse model of DYT1 dystonia overexpressing mutant torsinA. PDE10A is a key enzyme in the catabolism of second messenger cAMP and cGMP, whose synthesis is stimulated by D1 receptors and inhibited by D2 receptors preferentially expressed in striatoentopeducuncular/substantia nigra or striatopallidal pathways, respectively. PDE10A was studied in control mice (NT) and in mice carrying human wild-type torsinA (hWT) or mutant torsinA (hMT). Quantitative analysis of PDE10A expression was assessed in different brain areas by rabbit anti-PDE10A antibody immunohistochemistry and Western blotting. PDE10A-dependent cAMP hydrolyzing activity and PDE10A mRNA were also assessed. Striatopallidal neurons were identified by rabbit anti-enkephalin antibody.In NT mice, PDE10A is equally expressed in medium spiny striatal neurons and in their projections to entopeduncular nucleus/substantia nigra and to external globus pallidus. In hMT mice, PDE10A content selectively increases in enkephalin-positive striatal neuronal bodies; moreover, PDE10A expression and activity in hMT mice, compared with NT mice, significantly increase in globus pallidus but decrease in entopeduncular nucleus/substantia nigra. Similar changes of PDE10A occur in hWT mice, but such changes are not always significant. However, PDE10A mRNA expression appears comparable among NT, hWT, and hMT mice.In DYT1 transgenic mice, the inverse changes of PDE10A in striatoentopeduncular and striatopallidal projections might result over time in an imbalance between direct and indirect pathways for properly focusing movement. The decrease of PDE10A in the striatoentopeduncular/nigral projections might lead to increased intensity and duration of D1-stimulated cAMP/cGMP signaling; conversely, the increase of PDE10A in the striatopallidal projections might lead to increased intensity and duration of D2-inhibited cAMP/cGMP signaling.SIGNIFICANCE STATEMENT In DYT1 transgenic mouse model of dystonia, PDE10A, a key enzyme in cAMP and cGMP catabolism, is downregulated in striatal projections to entopeduncular nucleus/substantia nigra, preferentially expressing D1 receptors that stimulate cAMP/cGMP synthesis. Conversely, in DYT1 mice, PDE10A is upregulated in striatal projections to globus pallidus, preferentially expressing D2 receptors that inhibit cAMP/cGMP synthesis. The inverse changes to PDE10A in striatoentopeduncular/substantia nigra and striatopallidal pathways might tightly interact downstream to dopamine receptors, likely resulting over time to increased intensity and duration respectively of D1-stimulated and D2-inhibited cAMP/cGMP signals. Therefore, PDE10A changes in the DYT1 model of dystonia can upset the functional balance of basal ganglia circuits, affecting direct and indirect pathways simultaneously.


Stimulation of monocyte-mediated, antibody-dependent cytotoxicity in mycosis fungoides.
Antibody-dependent cytotoxicity mediated by purified blood monocytes were determined in untreated patients with plaque-stage mycosis fungoides (MF), parapsoriasis en plaques, exfoliating erythroderma, and noncutaneous malignant lymphoma. Compared with healthy control subjects and control subjects with varicose ulcers, patients with MF had increased monocyte cytotoxicity. In the other dermatoses, normal monocyte cytotoxicity was found. Patients with noncutaneous malignant lymphoma showed normal or decreased monocyte cytotoxicity. There was no evidence that abnormal monocyte cytotoxicity in cutaneous and noncutaneous malignant lymphoma were caused by interaction with lymphocytes or serum. The presence of increased monocyte cytotoxicity in patients with plaque-stage MF may be a clinically useful finding when this diagnosis is suspected clinically but not proved histopathologically.


Unprecedented enantio-selective live-cell mitochondrial DNA super-resolution imaging and photo-sensitizing by the chiral ruthenium polypyridyl DNA "light-switch".
Mitochondrial DNA (mtDNA) is known to play a critical role in cellular functions. However, the fluorescent probe enantio-selectively targeting live-cell mtDNA is rare. We recently found that the well-known DNA 'light-switch' [Ru(phen)2dppz]Cl2 can image nuclear DNA in live-cells with chlorophenolic counter-anions via forming lipophilic ion-pairing complex. Interestingly, after washing with fresh-medium, [Ru(phen)2dppz]Cl2 was found to re-localize from nucleus to mitochondria via ABC transporter proteins. Intriguingly, the two enantiomers of [Ru(phen)2dppz]Cl2 were found to bind enantio-selectively with mtDNA in live-cells not only by super-resolution optical microscopy techniques (SIM, STED), but also by biochemical methods (mitochondrial membrane staining with Tomo20-dronpa). Using [Ru(phen)2dppz]Cl2 as the new mtDNA probe, we further found that each mitochondrion containing 1-8 mtDNA molecules are distributed throughout the entire mitochondrial matrix, and there are more nucleoids near nucleus. More interestingly, we found enantio-selective apoptotic cell death was induced by the two enantiomers by prolonged visible light irradiation, and in-situ self-monitoring apoptosis process can be achieved by using the unique 'photo-triggered nuclear translocation' property of the Ru complex. This is the first report on enantio-selective targeting and super-resolution imaging of live-cell mtDNA by a chiral Ru complex via formation and dissociation of ion-pairing complex with suitable counter-anions.


A novel role for Lsc/p115 RhoGEF and LARG in regulating RhoA activity downstream of adhesion to fibronectin.
Adhesion of cells to extracellular matrix proteins such as fibronectin initiates signaling cascades that affect cell morphology, migration and survival. Some of these signaling pathways involve the Rho family of GTPases, such as Cdc42, Rac1 and RhoA, which play a key role in regulating the organization of the cytoskeleton. Although significant advances have been made in understanding how Rho proteins control cytoskeletal architecture, less is known about the signals controlling activation of the GTPases themselves. The focus of this study was to determine which guanine nucleotide exchange factor(s) are responsible for activation of RhoA downstream of adhesion to fibronectin. Using an affinity pulldown assay for activated exchange factors, we show that the RhoA-specific exchange factors Lsc/p115 RhoGEF and LARG are activated when cells are plated onto fibronectin, but not other exchange factors such as Ect2 or Dbl. Knockdown of Lsc and LARG together significantly decreases RhoA activation and formation of stress fibers and focal adhesions downstream of fibronectin adhesion. Similarly, overexpression of a catalytically inactive mutant of Lsc/p115 RhoGEF inhibits RhoA activity and formation of stress fibers and focal adhesions on fibronectin. These data establish a previously uncharacterized role for the exchange factors Lsc/p115 RhoGEF and LARG in linking fibronectin signals to downstream RhoA activation.


Calcium, calcium antagonists and experimental atherosclerosis.
Several calcium entry blockers have shown an antiatherosclerotic effect both in vitro and in vivo. The effects are particularly evident against smooth muscle cell migration multiplication, matrix formation, calcium and cholesterol accumulation. Among the new calcium antagonists, isradipine, amlodipine and lacidipine, are promising as antiatherosclerotic agents. Lacidipine is particularly interesting because of its lipophylic structure and accumulation in cell membranes. Lacidipine is structurally related to nifedipine; we observed that lacidipine inhibits three major processes of atherogenesis: cholesteryl ester metabolism in macrophages, proliferation of myocytes, and their migration.


Myelin-associated glycoprotein is a myelin signal that modulates the caliber of myelinated axons.
Myelination increases neuronal conduction velocity through its insulating properties and an unidentified extrinsic effect that increases axonal caliber. Although it is well established that demyelination can cause axonal atrophy, the myelin molecule that regulates axonal caliber is not known. Loss of the structural proteins of compact peripheral nervous system (PNS) myelin, P0 protein, and myelin basic protein does not lead to axonal atrophy. This study demonstrates that mice with a null mutation of the myelin-associated glycoprotein (MAG) gene have a chronic atrophy of myelinated PNS axons that results in paranodal myelin tomaculi and axonal degeneration. Absence of MAG was correlated with reduced axonal calibers, decreased neurofilament spacing, and reduced neurofilament phosphorylation. Because axonal atrophy and degeneration in MAG-deficient mice occur in the absence of inflammation, hypomyelination, significant demyelination-remyelination, or gain of function mutations, these data support a functional role for MAG in modulating the maturation and viability of myelinated axons.


Ascending placentitis in the mare: A review.
Ascending placentitis is a condition that occurs late in pregnancy when bacteria enter the sterile uterus from the lower reproductive tract. It leads to abortion or the birth of premature and weakened foals. Early detection and treatment of this condition is vital for ensuring the production of a viable foal.Mares with ascending placentitis often present in late term pregnancy with signs of premature udder development and premature lactation. There may be a vulvar discharge. Early detection of placental problems is possible using trans-abdominal or trans-rectal ultrasonography. Hormones such as progesterone and relaxin may be measured as indicators of foetal stress and placental failure. Postpartum foetal membranes may be thickened and contain a fibronecrotic exudate. The region most affected is the cervical star. Definitive diagnosis of ascending placentitis is by histopathological examination of the chorioallantoic membrane.Ideal treatment strategies are aimed at curing the infection and prolonging the pregnancy to as close to term as possible and consist of anti-microbials, anti-inflammatories and hormonal support.Swabs are taken from affected mares to determine antibiotic sensitivity and to aid in treatment of foals born from these mares which are at risk of becoming septic. If detected early enough, the chances of producing a viable foal are greatly increased.


Immunomodulatory effects of cyclophosphamide and implementations for vaccine design.
Drug repositioning refers to the utilization of a known compound in a novel indication underscoring a new mode of action that predicts innovative therapeutic options. Since 1959, alkylating agents, such as the lead compound cyclophosphamide (CTX), have always been conceived, at high dosages, as potent cytotoxic and lymphoablative drugs, indispensable for dose intensity and immunosuppressive regimen in the oncological and internal medicine armamentarium. However, more recent work highlighted the immunostimulatory and/or antiangiogenic effects of low dosing CTX (also called "metronomic CTX") opening up novel indications in the field of cancer immunotherapy. CTX markedly influences dendritic cell homeostasis and promotes IFN type I secretion, contributing to the induction of antitumor cytotoxic T lymphocytes and/or the proliferation of adoptively transferred T cells, to the polarization of CD4(+) T cells into TH1 and/or TH17 lymphocytes eventually affecting the Treg/Teffector ratio in favor of tumor regression. Moreover, CTX has intrinsic "pro-immunogenic" activities on tumor cells, inducing the hallmarks of immunogenic cell death on a variety of tumor types. Fifty years after its Food and Drug Administration approval, CTX remains a safe and affordable compound endowed with multifaceted properties and plethora of clinical indications. Here we review its immunomodulatory effects and advocate why low dosing CTX could be successfully combined to new-generation cancer vaccines.


Plane-wave basis finite elements and boundary elements for three-dimensional wave scattering.
Classical finite-element and boundary-element formulations for the Helmholtz equation are presented, and their limitations with respect to the number of variables needed to model a wavelength are explained. A new type of approximation for the potential is described in which the usual finite-element and boundary-element shape functions are modified by the inclusion of a set of plane waves, propagating in a range of directions evenly distributed on the unit sphere. Compared with standard piecewise polynomial approximation, the plane-wave basis is shown to give considerable reduction in computational complexity. In practical terms, it is concluded that the frequency for which accurate results can be obtained, using these new techniques, can be up to 60 times higher than that of the conventional finite-element method, and 10 to 15 times higher than that of the conventional boundary-element method.


[Physiological-ergonomic mechanism of the skeletal muscles].
The article deals with theoretical analysis of present data on physiology of muscular activity. This analysis helped to specify physiologic and ergonomic mechanism of skeletal muscles work. The authors prove this physiologic and ergonomic mechanism to result from known mechanic and chemical processes in muscular tissue structures. Those mechanic and chemical processes underlie well-known molecular theories of muscular contraction. The physiologic and ergonomic mechanism includes change in elasticity basic for mechanic models and theories of muscular work, so this mechanism appears superior to other models and theories explaining muscular activity. Physiologic and ergonomic mechanism of muscular work appeared to be genetically linked with morphologic and functional differentiation of locomotory units, with presence of specific muscular zones different in contraction and tensile strain.


[Susceptibility to damage of human lymphocyte chromosomes in different stages of the mitotic cycle when exposed to fast neutrons with an average energy of 6 MeV].
Cytogenetic susceptibility of human lymphocytes in the culture to lesion is studied under the effect of neutrons with 6 MeV energy at different stages of the mitotic cycle. Radiosensitivity of human lymphocytes under the influence of gamma-quanta and neutrons is found to vary identically during the whole cycle. These variations are less expressed in the case of neutron irradiation. The data allow concluding that the repair system functions most actively at the S stage in case of both types of radiation.


Tris(cyclo-hexyl-ammonium) cis-di-chlorido-bis-(oxalato-κ(2) O (1),O (2))stann-ate(IV) chloride monohydrate.
The crystal structure of the title compound, (C6H14N)3[Sn(C2O4)2Cl2]Cl·H2O, contains three cyclo-hexyl-ammonium cations, one stannate(IV) dianion, one isolated chloride anion and one lattice water mol-ecule. The cyclo-hexyl-ammonium cations adopt chair conformations. In the complex anion, two bidentate oxalate ligands and two chloride anions in cis positions coordinate octa-hedrally to the central Sn(IV) atom. The cohesion of the mol-ecular entities is ensured by the formation of N-H⋯O, O-H⋯O, O-H⋯Cl and N-H⋯Cl inter-actions involving cations, anions and the lattice water mol-ecule, giving rise to a layer-like arrangement parallel to (010).


Rubella immunisation: whose baby?
Only half of girls aged from 11 to 14 years in a new town practice of 11 200 patients were recorded as immunised against rubella in 1979. The practice then assumed responsibility for its rubella immunisations and in four years, by using an age-sex register, achieved a 91% uptake of vaccine in the under 14s. In the over 14s, the practice reduced the number of "rubella risk" patients from 49% to 16%. It is suggested that general practitioners are best placed to implement the rubella immunisation programme successfully, though they will need to be renumerated adequately for this time consuming work.


No Significant Differences in Muscle Growth and Strength Development When Consuming Soy and Whey Protein Supplements Matched for Leucine Following a 12 Week Resistance Training Program in Men and Women: A Randomized Trial.
There are conflicting reports regarding the efficacy of plant versus animal-derived protein to support muscle and strength development with resistance training. The purpose of this study was to determine whether soy and whey protein supplements matched for leucine would comparably support strength increases and muscle growth following 12 weeks of resistance training. Sixty-one untrained young men (n = 19) and women (n = 42) (18-35 year) enrolled in this study, and 48 completed the trial (17 men, 31 women). All participants engaged in supervised resistance training 3×/week and consumed 19 grams of whey protein isolate or 26 grams of soy protein isolate, both containing 2 g (grams) of leucine. Multi-level modeling indicated that total body mass (0.68 kg; 95% CI: 0.08, 1.29 kg; p < 0.001), lean body mass (1.54 kg; 95% CI: 0.94, 2.15 kg; p < 0.001), and peak torque of leg extensors (40.27 Nm; 95% CI: 28.98, 51.57 Nm, p < 0.001) and flexors (20.44 Nm; 95% CI: 12.10, 28.79 Nm; p < 0.001) increased in both groups. Vastus lateralis muscle thickness tended to increase, but this did not reach statistical significance (0.12 cm; 95% CI: -0.01, 0.26 cm; p = 0.08). No differences between groups were observed (p > 0.05). These data indicate that increases in lean mass and strength in untrained participants are comparable when strength training and supplementing with soy or whey matched for leucine.


Clinical value of the low-grade inflammation score in aneurysmal subarachnoid hemorrhage.
Multiple inflammatory biomarkers have been shown to predict symptomatic cerebral vasospasm (SCVS) and poor functional outcome in patients with aneurysmal subarachnoid hemorrhage. However, the impact of the low-grade inflammation (LGI) score, which can reflect the synergistic effects of five individual inflammatory biomarkers on SCVS and poor functional outcome on aneurysmal subarachnoid hemorrhage (aSAH), has not yet been well established. The aim of this study was to evaluate the impact of the LGI score on SCVS and poor functional outcome in aSAH patients. The LGI score was calculated as the sum of 10 quantiles of each individual inflammatory biomarker. The association of the LGI score with the risk of SCVS and poor functional outcome was analyzed with multivariate logistical regression. A total of 270 eligible aSAH patients were included in this study: 74 (27.4%) had SCVS, and 79 (29.3%) had poor functional outcomes. After adjusting for confounders, a higher LGI score was revealed to independently predict SCVS (OR, 1.083; 95% CI, 1.011-1.161; P = 0.024) and poor functional outcome (OR, 1.132; 95% CI, 1.023-1.252; P = 0.016), and the second and third tertile group had higher risk of SCVS than lowest tertile group (OR, 2.826; 95% CI, 1.090-7.327; P = 0.033) (OR, 3.243; 95% CI, 1.258-8.358; P = 0.015). The receiver operating characteristic (ROC) curve uncovered the ability of the LGI score to distinguish patients with and without SCVS (area under the curve [AUC] = 0.746; 95% CI, 0.690-0.797; P < 0.001) and poor functional outcomes (area under the curve [AUC] = 0.799; 95% CI, 0.746-0.845; P < 0.001), the predictive value of LGI on SCVS and poor functional outcome is superior than PLT, NLR and WBC, but there was no statistical difference between LGI and CRP for predicting SCVS (P = 0.567) and poor functional outcome (P = 0.171). A higher LGI which represents severe low grade inflammation status is associated with SCVS and poor functional outcome at 3 months after aSAH.


The use of knee mega-prosthesis for the management of distal femoral fractures: A systematic review.
Distal femur fractures (DFFs) are unusual and difficult to deal, especially in elderly patients. A consensus about a gold-standard treatment has not been reached yet. Available options include both conservative and surgical management. In elderly patients a prosthetic replacement could be a valid treatment option. Literature is lacking about the use of mega-prosthesis in this type of fractures. The purpose of the present systematic review is to examine which fracture, both acute and chronic, involving distal femur should be treated by using a mega-prosthesis. Studies were identified by searching electronic databases. All studies that enrolled people of any age affected by a DFFs treated by using a megaprosthesis were included. Primary outcomes of the present reviews were: ROM, functional assessment and complications. Two review authors independently selected eligible trials. Disagreements at any stage were resolved by consensus or a third party adjudication. Descriptive statics was used to summarize the data. Thirteen article were finally included in the review. One hundred-four patients were treated with knee megaprosthesis. Three categories of patients were identified: 29 patients were affected by supracondylar femur fracture; 51 patients occurred with a periprosthetic fracture; 24 patients suffered a non-union of a previous supracondylar fracture. The follow-up varied between 6 months to 58 months. All studies showed good results in terms of improving quality of life, resuming activities of daily living (ADLs), early mobilization, ROM, shorter hospital stay. Although not frequent, the only reported complications were infection and aseptic loosening. The present review showed that the use of knee megaprosthetic implants could represent a valid treatment option aiming to reduce patients' immobilitazion and hospital stay. Good clinical outcomes with low rate of complications were reported by all included studies. Literature is lacking about long-term outcomes and complications. Moreover studies comparing knee prostheses and other types of surgical treatment (intramedullary nails, plate fixation system) are needed. Megaprosthesis represent a viable treatment option in patients affected by DFFs (either acute, periprostethic or non-union) because they allow immediate weight-bearing, shorter hospital stay, a fast recovery of knee function and ADLs.


Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle.
Asexual blood stages of the malaria parasite, which cause all the pathology associated with malaria, can readily be genetically modified by homologous recombination, enabling the functional study of parasite genes that are not essential in this part of the life cycle. However, no widely applicable method for conditional mutagenesis of essential asexual blood-stage malarial genes is available, hindering their functional analysis. We report the application of the DiCre conditional recombinase system to Plasmodium falciparum, the causative agent of the most dangerous form of malaria. We show that DiCre can be used to obtain rapid, highly regulated site-specific recombination in P. falciparum, capable of excising loxP-flanked sequences from a genomic locus with close to 100% efficiency within the time-span of a single erythrocytic growth cycle. DiCre-mediated deletion of the SERA5 3' UTR failed to reduce expression of the gene due to the existence of alternative cryptic polyadenylation sites within the modified locus. However, we successfully used the system to recycle the most widely used drug resistance marker for P. falciparum, human dihydrofolate reductase, in the process producing constitutively DiCre-expressing P. falciparum clones that have broad utility for the functional analysis of essential asexual blood-stage parasite genes.


Human Auditory Fast and Slow Omitted Stimulus Potentials and Steady-State Responses.
Two kinds of omitted stimulus potentials (OSP) are called "fast" and "slow." Fast OSPs, recently found with visual stimuli, are here extended to auditory; they occur after omissions or after the end of trains of 1 to >20 Hz clicks. Slow OSPs, long known, follow trains of 0.3 to 4 Hz. Each has its constant peak latency after the due-time of the first missing stimulus, as though the system is expecting something quite accurately on schedule. They differ in dynamics and slow OSPs require the subject to attend; fast OSPs do not. Steady-state responses (SSR) at a critical click rate of 6-7 Hz sometimes appear to alternate between two forms and OSPs may depend on which they follow. Fast OSPs can occur to the first, second and even the third omissions after the end of a train. Short conditioning periods suffice. Irregular interstimulus intervals do not reduce fast OSPs but attenuate slow OSPs.


Vascular access for intensive maintenance hemodialysis: a systematic review for a Canadian Society of Nephrology clinical practice guideline.
Practices in vascular access management with intensive hemodialysis may differ from those used in conventional hemodialysis. We conducted a systematic review to inform clinical practice guidelines for the provision of intensive hemodialysis. Adult patients receiving maintenance (>3 months) intensive hemodialysis (frequent [≥5 hemodialysis treatments per week] and/or long [>5.5 hours per hemodialysis treatment]). We searched EMBASE and MEDLINE (1990-2011) for randomized and observational studies. We also searched conference proceedings (2007-2011). (1) Central venous catheter (CVC) versus arteriovenous (AV) access, (2) buttonhole versus rope-ladder cannulation, (3) topical antimicrobial cream versus none in buttonhole cannulation, and (4) closed connector devices among CVC users. Access-related infection, survival, hospitalization, patency, access survival, intervention rates, and quality of life. We included 23, 7, and 5 reports describing effectiveness by access type, buttonhole cannulation, and closed connector device, respectively. No study directly compared CVC with AV access. On average, bacteremia and local infection rates were higher with CVC compared with AV access. Access intervention rates were higher with more frequent hemodialysis, but access survival did not differ. Buttonhole cannulation was associated with bacteremia rates similar to those seen with CVCs in some series. Topical mupirocin seemed to attenuate this effect. No direct comparisons of closed connector devices versus standard luer-locking devices were found. Low rates of actual or averted (near misses) air embolism and bleeding were reported with closed connector devices. Overall, evidence quality was very low. Limited direct comparisons addressing main review questions, small sample sizes, selective outcome reporting, publication bias, and residual confounding were major factors. This review highlights several differences in the management of vascular access in conventional and intensive hemodialysis populations. We identify a need for standardization of vascular access outcome reporting and a number of priorities for future research.


Performance on the Cogstate Brief Battery Is Related to Amyloid Levels and Hippocampal Volume in Very Mild Dementia.
In a group of older adults with very mild dementia, we aimed to characterize the nature and magnitude of cognitive decline as measured by the Cogstate Brief Battery, in relation to Aβ levels and hippocampal volume. Participants were characterized according to their status on the Clinical Dementia Rating (CDR) scale. A total of 308 individuals who were CDR 0 and had low cerebral Aβ levels (Aβ-), 32 individuals who were Aβ- and CDR 0.5, and 43 individuals who were Aβ+ and CDR 0.5 were included in this study. Participants completed the CogState brief battery at baseline, and at 18-, 36-, 54- and 72-month follow-up. Linear mixed model analyses indicated that relative to the Aβ- CDR 0 group, the Aβ+ CDR 0.5 group showed increased rates of memory decline and hippocampal volume loss. However, compared to the Aβ- CDR 0 group, the Aβ- CDR 0.5 group showed no changes in cognitive function or hippocampal volume over 72 months. The results of this study confirm that in individuals with very mild dementia, who also have biomarker confirmation of Aβ+, changes in cognitive function manifest primarily as deterioration in memory processing, and this is associated with hippocampal volume loss. Conversely, the absence of any cognitive decline or loss in hippocampal volume in individuals with very mild dementia but who are Aβ- suggests that some other non-AD disease process may underlie any static impairment in cognitive function.


A monoclonal antibody (BIP 45) detects Ag(c,g) polymorphism of human apolipoprotein B.
A monoclonal antibody (BIP 45) against human apolipoprotein B (apo B) was used to study the polymorphism of apo B in families and in unrelated subjects. BIP 45 bound to apo B-containing lipoprotein particles in one of three distinct patterns of immunoreactivity (strong, weak and intermediate). Family studies showed that these binding patterns result from co-dominant transmission of apo B allelic pairs which are temporarily designated allele BIP- and allele BIP+; allele BIP+ would code for the apo B BIP 45 epitope. Analysis of plasma samples from 244 unrelated men randomly chosen from the North French population indicated that 46.7% of them bound BIP 45 with low affinity (weak reactors), 44.7% with intermediate affinity (intermediate reactors) and 8.6% with high affinity (strong reactors). According to the Hardy-Weinberg equilibrium, this corresponds to gene frequencies of 0.690/0.310 for the type BIP-/BIP+ alleles. This corresponds to the gene frequencies of 0.695/0.305 at the Ag(g)/Ag(c) locus previously found in a Caucasian population. Furthermore, the investigation of Ag(c,g) and of monoclonal BIP 45 antibody immunoaffinity for 30 individual plasma samples showed that BIP 45 bound strongly to Ag(c) factor, whereas it bound weakly to the allelic Ag(g) factor. This monoclonal antibody will be useful for the detection of the two corresponding apo B species designated apo B (Ag(c) factor, BIP+) and apo B (Ag(g) factor, BIP-).


Epithelial dysplasia in atrophic gastritis. Bioptical follow-up study.
Fifty-nine cases of gastric dysplasia (46 of which were mild, 11 moderate and 2 severe) were studied in relation to their association with atrophic gastritis and intestinal metaplasia. Atrophic gastritis was found in 39 cases (28 of which were mild, 10 moderate and 1 severe). Dysplasia was considered "persistent" when found of the same degree in at least two consecutive check-ups after initial diagnosis (13 cases); it was considered "progressive" if found more severe or evolving as cancer (5 cases) or "regressive" if detected in a lesser degree or no longer detected (13 cases). Sixteen of the 18 persistent or progressive cases of dysplasia were associated with atrophic gastritis, whereas 10 of the 13 cases with regressive dysplasia revealed no concomitant pattern of gastric mucosa atrophy (p less than 0.005). These findings suggest that dysplasia represents a truly pre-neoplastic change particularly when associated with atrophic gastritis and which must therefore be more carefully monitored.


Switched memory B cells maintain specific memory independently of serum antibodies: the hepatitis B example.
The immunogenicity of a vaccine is conventionally measured through the level of serum Abs early after immunization, but to ensure protection specific Abs should be maintained long after primary vaccination. For hepatitis B, protective levels often decline over time, but breakthrough infections do not seem to occur. The aim of this study was to demonstrate whether, after hepatitis B vaccination, B-cell memory persists even when serum Abs decline. We compared the frequency of anti-hepatitis-specific memory B cells that remain in the blood of 99 children five years after priming with Infanrix -hexa (GlaxoSmithKline) (n=34) or with Hexavac (Sanofi Pasteur MSD) (n=65). These two vaccines differ in their ability to generate protective levels of IgG. Children with serum Abs under the protective level, <10 mIU/mL, received a booster dose of hepatitis B vaccine, and memory B cells and serum Abs were measured 2 wk later. We found that specific memory B cells had a similar frequency in all children independently of primary vaccine. Booster injection resulted in the increase of memory B cell frequencies (from 11.3 in 10(6) cells to 28.2 in 10(6) cells, p<0.01) and serum Abs (geometric mean concentration, GMC from 2.9 to 284 mIU/mL), demonstrating that circulating memory B cells effectively respond to Ag challenge even when specific Abs fall under the protective threshold.


Characterization of malignant focal liver lesions with contrast-enhanced 40 MHz ultrasound imaging in hepatitis B virus X transgenic mice: a feasibility study.
Contrast-enhanced ultrasound (CEUS) imaging has been a reliable clinical method of detecting three vascular contrast phases and characterizing focal liver lesions. Previous results were all from human (i.e., clinical studies). The main purpose of this study was to extend this to small animals and to investigate the feasibility of using CEUS in preclinical research. Specifically, high-frequency (40 MHz) ultrasound liver imaging with albumin-shelled microbubbles was employed to detect the three vascular contrast phases and characterize focal liver lesions that developed in thirteen Hepatitis B virus X (HBx) transgenic mice at around 14 to 16 months of age. Previous studies indicated that 90-100% incidence of hepatocellular carcinoma (HCC) was observed in HBx transgenic male mice. After injecting the contrast agent, the time-intensity curves (TICs) of focal liver lesions, vessels in focal liver lesions and surrounding liver parenchyma tissues were measured for 30 minutes. The peak of mean intensity relative to the baseline increased 7.36 dB (p < 0.02). On the other hand, the mean contrast between the focal liver lesion and the liver parenchyma increased by 7.74 (p < 0.05) dB, thus allowing clear detection ofthe lesion margin. Histopathology investigations confirmed the development of the lesion in these mice. In addition, guidelines of European Federation of Societies for Ultrasound in Medicine and Biology were followed as an attempt to characterize features of the TICs in mice. The arterial phase was defined as 2 to 60 seconds post contrast injection, and the parenchyma phase was defined as the time period from 10 to 30 minutes post contrast injection. Comparing the imaging with the pathology results, the sensitivity, specificity and accuracy of CEUS for the detection of malignant focal liver lesion in HBx transgenic mice were 91%, 100% and 92%. These results demonstrated that high-frequency CEUS imaging potentially can be used for detecting the three vascular contrast phases of malignant focal liver lesions and characterizing malignant focal liver lesions in mice. Thus can be a valuable tool in preclinical research.


Hybrid Electrically Conductive Hydrogels with Local Nerve Growth Factor Release Facilitate Peripheral Nerve Regeneration.
It is challenging to treat peripheral nerve injury (PNI) clinically. As the gold standard for peripheral nerve repair, autologous nerve grafting remains a critical limitation, including tissue availability, donor-site morbidity, immune rejection, etc. Recently, conductive hydrogels (CHs) have shown potential applications in neural bioengineering due to their good conductivity, biocompatibility, and low immunogenicity. Herein, a hybrid electrically conductive hydrogel composed of acrylic acid derivatives, gelatin, and heparin with sustained nerve growth factor (NGF) release property was developed. The rat sciatic nerve injury (SNI) model (10 mm long segment defect) was used to investigate the efficacy of these hydrogel conduits in facilitating peripheral nerve repair. The results showed that the hydrogel conduits had excellent conductivity, mechanical properties, and biocompatibility. In addition, NGF immobilized in the hydrogel conduits had good sustained release characteristics. Finally, functional recovery and electrophysiological evaluations, together with histological analysis, indicated that the hydrogel conduits immobilizing NGF had superior effects on motor recovery, axon growth, and remyelination, thereby significantly accelerating the repairing of the sciatic nerve. This study demonstrated that hybrid electrically conductive hydrogels with local NGF release could be effectively used for PNI repair.


Loss anxiety: an alternative explanation for the fundamental fears in human beings.
In this article, fear of loss as well as fear of death are introduced to explain cultural worldview defence reactions of individuals. Participants were subjected to mortality salience, disability salience and control conditions. Mortality salience and paralysis salience were found to lead to a change in conservatism scores. In a qualitative follow-up study, when reminded about mortality, the participants reported less individual sadness than expected; whereas when the participants were reminded about paralysis, greater individual sadness was reported. Any kind of loss manipulation that is moderately fearful, highly imaginable, and highly self-relevant is suggested to affect cultural worldview defence reactions.


Administrative databases and clinical governance: The case of COPD.
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. However, COPD is still underdiagnosed, undertreated, and not sufficiently prevented. Health administrative databases provide a powerful way of studying COPD in the population. This retrospective study used administrative data, collected during 2011 and 2012, retrieved from 3 Italian local health authorities (LHAs). The analysis through administrative databases allowed firstly to identify patients with COPD receiving services by the 3 LHAs: The estimated average is ~3% of the population aged ≥40 years. Furthermore, it was also possible to stratify patients by investigating the health consumption in hospitalization for COPD and use of respiratory drugs. In all 3 LHA patients with moderate COPD were the majority of the population with COPD. Finally, it was possible to distinguish patients who made an appropriate use of SABA (76% of the total), patients who had a potentially inappropriate use (20%), and those with an overuse of SABA (4%). The use of SABA consumption patterns can be a reliable proxy variable to detect subgroups who may necessitate therapy revision. Health administrative databases seem beneficial for planning health care interventions, including the COPD field. They are robust information systems subjected to regular data quality controls remaining the prevalent data source, reliable because of the amount of data and the population coverage, especially in countries with a National Health Service System.


Comparison of chiropractic and hospital outpatient management of low back pain: a feasibility study. Report of a working group.
This is the report of a feasibility study of a randomised controlled trial of chiropractic and hospital outpatient management for low back pain of mechanical origin. Preparations for the study included an approach to the General Medical Council for guidance about the intended collaboration between medically qualified and heterodox practitioners, detailed communication with local general practitioners, and the provision of a Medical Research Council (MRC) grant to cover payments to the chiropractors for work carried out in the course of the study. A total of 238 patients were considered, 197 of whom had initially presented to Northwick Park Hospital and the remaining 41 to the chiropractic clinic in Harrow. Only 6% of the patients presenting to the hospital refused to enter. The single most frequent reason for ineligibility in the hospital patients was freedom from pain at the time of the first hospital visit (23%). A variety of medical contraindications accounted for the exclusion of a further 24% of hospital patients. Patients presenting to the chiropractic group tended to have had shorter current episodes of back pain but to have had more NHS treatment in the past than those presenting to hospital. The commonest reason for exclusion among those presenting to the chiropractic clinic was refusal to enter (34%). Only 5% of the chiropractic patients were ineligible for medical reasons. Overall, 16% of those presenting to hospital and 44% of those presenting to the chiropractors were eligible and willing to enter the randomised treatment phase of the study. Of the 50 patients who entered the treatment phase, all but seven completed treatment and the six weekly self-completed assessments of progress. Patients whose current episodes had lasted less than a month progressed significantly more rapidly than those with longer current episodes. It is likely that sufficient numbers of patients with low back pain are prepared to take part in a formal randomized controlled trial. The organization and working methods for such a trial appear to be feasible. A full scale multicentre trial should aim to include about 2000 patients.


BRCA patients in Cuba, Greece and Germany: Comparative perspectives on public health, the state and the partial reproduction of 'neoliberal' subjects.
The relationship among genetic technologies, biosocial identity and patient subjectivity has been the focus of an increasing range of social science literature. Examining mainly European and North American contexts this work has demonstrated the variable configurations of genetic knowledge-practices and the diverse implications for at-risk individuals and populations. This article brings together ethnographic research on genomic medicine, public health and breast cancer in Cuba, Greece and Germany. Although each case study addresses different publics/patients, institutional settings and risk-related practices, they all critically examine 'neoliberal' subjectivity and BRCA patienthood, at the intersection of political rationalities, medical discourses, social conditions and moral codes. In the Cuban case, cultural articulations of inherited and other embodied risks relating to breast cancer are analysed in relation to state provision of 'community genetics', and the shifting dynamics of public health in response to global social processes. The Greek case explores how culturally embedded values, notions of inherited risk and care inform or are re-articulated through institutional practices and ambivalent subject positions, at the meeting point between individualised medicine, religious philanthropy and the particularities of public health. In the German context, diverging patient subjectivities are examined against the background of prevailing social discourses and institutionalised risk management practices that promote proactive individuality. Drawing on deconstructive and feminist analyses, these case studies reveal how normative 'neoliberal' patient subjects are only 'partially reproduced' in situated contexts, neither stable nor homogeneous, as different actors and publics variously articulate, embrace or engage with transnational as well as culturally embedded discourses and health practices.


Malignant lesions of the ovary in childhood.
Approximately half of all lesions of the ovary in childhood are neoplastic, yet only a small fraction of neoplastic lesions contain malignant elements. Overall, malignancies of the ovary account for 10% of all ovarian masses and 1% of childhood cancers. Primary ovarian malignancies fall into three broad categories based on the cell type of origin. Germ cell tumors predominate and may be further subdivided based on the differentiation of the malignant cells. Epithelial cell tumors, which are most common in adults, and sex-cord stromal tumors each make up 15% of the total in children. Rare malignant lesions and metastatic disease account for the small remaining group of tumors. Regardless of tumor type, the majority of patients present with localized disease, but proper surgical staging is important to determine the need for adjuvant therapy. The development of platinum-based chemotherapeutic regimens has resulted in significant improvements in long-term survival, even for children who present with advanced stage disease.


Mesoscale description of an asymmetric lamellar phase.
The relationship between the parameters in a description based on a mesoscale free energy functional for the concentration field and the macroscopic properties, such as the bending and compression moduli and the permeation constant, are examined for an asymmetric lamellar phase where the mass fractions of the hydrophobic and hydrophilic parts are not equal. The difference in the mass fractions is incorporated using a cubic term in the free energy functional, in addition to the usual quadratic and quartic terms in the Landau-Ginsburg formulation. The relationship between the coefficient of the cubic term and the difference in the mass fractions of the hydrophilic and hydrophobic parts is obtained. For a lamellar phase, it is important to ensure that the surface tension is zero due to symmetry considerations. The relationship between the parameters in the free energy functional for zero surface tension is derived. When the interface between the hydrophilic and hydrophobic parts is diffuse, it is found that the bending and compression moduli, scaled by the parameters in the free energy functional, do increase as the asymmetry in the bilayer increases. When the interface between the hydrophilic and hydrophobic parts is sharp, the scaled bending and compression moduli show no dependence on the asymmetry in the bilayer. The ratio of the permeation constant in between the water and bilayer in a molecular description and the Onsager coefficient in the mesoscale description is O(1) for both sharp and diffuse interfaces and it increases as the difference in the mass fractions is increased.