Botanical identification of medicinal roots collected and traded in Morocco and comparison to the existing literature.
A literature review revealed heavy reliance on a few key publications for identification of medicinal plant species from local or vernacular names and a lack of citation of voucher specimens in many publications. There is a need for more reliable and standardized data on the identity of species used for medicine, especially because local names vary from region to region. This is especially true in the case of medicinal roots, for which identification of species is difficult. This paper contributes to existing data on the species sold as medicinal roots (and other underground plant parts such as bulbs, corms, rhizomes and tubers) in Morocco. Data were collected in collaboration with herbalists in Marrakech and collectors in rural regions near Marrakech where species are collected from the wild. The ethno-medicinal uses of these species were also recorded. We identified the vernacular names for 67 medicinal roots (by free listing) used to treat a variety of human diseases. We were able to collect and identify one or more species for 39 of the recorded vernacular names. The ones we were not able to identify were either imported or no longer available in the markets. We collected more than one species for some of the vernacular names for a total of 43 species. We identified six new vernacular names and four species which had not been previously described in the literature. Our botanical identification matched at least one of the names listed in the literature 63% of the time and did not match any species listed in the literature 37% of the time. Of the three most commonly cited pieces of literature we compared to, we found the greatest overlap with the broader, more comprehensive work of Bellakhdar 1997 (as opposed to Benchâabane and Abbad 1997 which worked in a similarly focused geographical area). However there was only 63% agreement between Bellakhdar 1997 and our botanical identifications, and 29% of the time our identification didn't match even the genus of any of the species listed in any of the 3 most commonly cited pieces of literature. More rigorous methodology and reporting are needed for medicinal plant research in Morocco. This will ensure that studies are comparable, help to protect traditional medicine users from negative health effects, and, support efforts to conserve overharvested wild medicinal plants.


Platform-Switching for Cemented Versus Screwed Fixed Dental Prostheses: Reliability and Failure Modes: An In Vitro Study.
The aim of this study was to evaluate the probability of survival of cemented and screwed three-unit implant-supported fixed dental prostheses (ISFDP) using different implant-abutment horizontal matching configurations (regular vs switching platforms). One hundred and sixty-eight implants with internal hexagon connection (4 mm diameter, 10 mm length, Emfils; Colosso Evolution System, Itú, SP, Brazil) were selected for this study according to the horizontal implant-abutment matching configuration (regular or switching) and retention method and divided in four groups (n = 21 per group) as follows: 1) regular platform cemented (IRC); 2) or screw-retained (IRS); 3) switched-platform cemented (ISC); or 4) screw-retained (ISS). Regular and platform-switched abutments (Colosso evolution, 4 mm and 3.3 mm, respectively) were torqued, and 84 three-unit metal bridges were fabricated (first molar pontic). Implants were embedded in polymethyl-methacrylate resin and subjected to step-stress accelerated life testing in water. Weibull distribution was used to determine the probability of survival for a mission of 100,000 cycles at 400 N (90% two-sided confidence intervals). Polarized light and scanning electron microscopes were used for fractographic analysis. The β values of 0.50, 1.19, 1.25, and 1.95 for groups IRC, IRS, ISC, and ISS respectively, indicated that fatigue accelerated the failure for all groups, except IRC. The cement-retained groups presented significantly higher probability of survival (IRC - 98%, ISC - 59%) than screw-retained groups (IRS - 23% and ISS - 0%). Screw-retained FDPs exclusively failed by abutment-screw fractures, whereas cement-retained presented implant/screw/abutment fractures. The probability of survival of cement-retained ISFDP was higher than screw-retained, irrespective of implant-abutment horizontal configuration.


Biologic width around different implant-abutment interface configurations. A radiographic evaluation of the effect of horizontal offset and concave abutment profile in the canine mandible.
The purpose of this experimental study was to analyze radiographically in a dog model how different implant-abutment interface configurations influence alveolar crestal bone changes. Six different experimental implant-abutment connections were evaluated in six mixed-breed dogs. The following parameters were tested: absence of microgap, microgap proximal to bone crest, and microgap distant from bone crest. In addition, two different cervical abutment profiles, one straight and one featuring a supracrestal concavity, were evaluated. Implants were based on a cylindrical full-body screw design and made from cold-worked grade IV commercially pure titanium. The diameter (at thread tips) measured 4.1 mm, whereas the inner diameter was 3.5 mm. Standardized periapical digital radiographs were obtained for comparative analysis at baseline and at 3, 4, 5, 6, 7, 8, and 9 months after implant placement. Radiographs were randomized and calibrated for linear measurements. For statistical analysis, mixed-model repeated-measures analysis of variance was used. All implants integrated successfully and remained stable during the entire period of the study. Radiographically, when comparing groups with straight profiles, crestal bone remodeling in group C (one-piece design) was significantly less than in group A (matching diameters) and B (nonmatching diameters). In fact, implant group C showed the least crestal bone remodeling of all groups. When comparing groups with a concave profile but different microgap configurations, all three designs demonstrated bone loss with no significant differences among the three groups. A nonsubmerged one-piece implant design demonstrated the least amount of bone remodeling of all groups. Implant-abutment connections with a concave profile established crestal bone levels immediately apical to the concavity regardless of the microgap variable.


Hyperexcitability in young iPSC-derived C9ORF72 mutant motor neurons is associated with increased intracellular calcium release.
A large hexanucleotide repeat expansion in the C9ORF72 gene is the most prevalent cause of amyotrophic lateral sclerosis (ALS). To better understand neuronal dysfunction during ALS progression, we studied motor neuron (MN) cultures derived from iPSC lines generated from C9ORF72 (C9) expansion carriers and unaffected controls. C9 and control MN cultures showed comparable mRNA levels for MN markers SMI-32, HB9 and ISL1 and similar MN yields (> 50% TUJ1/SMI-32 double-positive MNs). Using whole-cell patch clamp we showed that C9-MNs have normal membrane capacitance, resistance and resting potential. However, immature (day 40) C9-MNs exhibited a hyperexcitable phenotype concurrent with increased release of calcium (Ca2+) from internal stores, but with no changes to NaV and KV currents. Interestingly, this was a transient phenotype. By day 47, maturing C9-MNs demonstrated normal electrophysiological activity, displaying only subtle alterations on mitochondrial Ca2+ release. Together, these findings suggest the potential importance of a developmental component to C9ORF72-related ALS.


Adherence with bisphosphonate therapy and change in bone mineral density among women with osteoporosis or osteopenia in clinical practice.
In clinical practice, adherence with bisphosphonate therapy varies greatly among women with osteoporosis or osteopenia. Our study suggests that better adherence with bisphosphonates confers tangible benefits in terms of graded increases in bone mineral density. Interventions to improve drug adherence should be an important component of disease management. In clinical trials, bisphosphonates have been found to increase bone mineral density (BMD) in women with osteoporosis or osteopenia. In clinical practice, where drug adherence is more variable, change in BMD with bisphosphonate therapy-overall and by level of adherence-is largely unknown. A retrospective cohort study was conducted at Henry Ford Health System (Detroit, MI, USA). Study subjects were women who had low BMD at the left total hip (T-score<-1.0), began oral bisphosphonate therapy, and had ≥1 BMD measurements at the left total hip≥6 months following treatment initiation. Change in BMD was calculated between the most recent pretreatment scan and the first follow-up scan. Adherence (i.e., medication possession ratio (MPR)) was measured from therapy initiation to the first follow-up scan. Among 644 subjects, mean age was 66 years, pretreatment BMD was 0.73 g/cm2, and pretreatment T-score was -1.8. Over a mean follow-up of 27.1 months, mean MPR was 0.57 (95% CI, 0.54 and 0.59), and mean percentage change in BMD was 1.5% (1.1 and 1.9%). Within the MPR strata (five consecutive equi-intervals, from low (0-0.19) to high (0.80-1.0)), mean change in BMD was -0.8% (-1.6 and 0.1%), 0.7% (-0.3 and 1.7%), 2.1% (1.1 and 3.0%), 2.1% (1.4 and 2.9%), and 2.9% (2.3 and 3.5%), respectively. In adjusted analyses, percentage change in BMD was higher (by 1.4-3.4%, p<0.05 for all) in the highest four MPR intervals, respectively, versus MPR 0-0.19. Among women with osteoporosis or osteopenia in clinical practice, better adherence with bisphosphonates appears to confer tangible benefits in terms of increases in BMD.


First Report of a Root Rot Caused by Phytophthora palmivora on Lavandula angustifolia in Turkey.
English Lavender (Lavandula angustifolia Mill.) has been considered an alternative crop to tobacco in Hatay Province of Turkey because of its great production potential. As a new, nonnative crop, diseases and pests of lavender are not well known in the region. In summer 2010, root rot symptoms were observed with an average incidence of 45% in a 2-year-old lavender nursery in Hatay. Initial symptoms of chlorosis and wilting were followed by progressive death of the plants starting at the shoot tips. An oomycetous species was isolated consistently from the stems and roots of diseased plants on potato dextrose agar (PDA) amended with several fungicides and antibiotics. The culture of the single-zoospore isolate produced arachnoid growth on PDA. Chlamydospores of the isolate were approximately 35.0 μm in diameter. The isolate produced papillate, caduceus, hyaline sporangia in different shapes ranging from spherical to ellipsoidal. Sporangia with short pedicels (5 μm) were 35.0 to 57.5 × 27.5 to 42.5 μm with a length/width ratio of 1.2 to 1.8. On the basis of symptoms and morphology of the organism, the pathogen was identified as Phytophthora palmivora (E.J. Butler) E.J. Butler (3). Identification of the isolate was also confirmed by comparison of the sequence of the nuclear ribosomal internal transcribed spacer (ITS) region with reference isolates. The ITS region of rDNA was amplified by PCR with primers ITS1/ITS4 and sequenced (GenBank Accession No. JF777117). BLAST analysis of the sequence obtained showed a 99 to 100% homology with P. palmivora. Pathogenicity tests were performed on 12 greenhouse-grown 2-year-old lavender plants in 2-liter pots containing a steamed sand/peat/soil mixture. After rooting, the plants were inoculated by placing mycelial plugs from a 1-week-old culture of the isolate into an incision made at the base of each plant. Control plants were treated with plugs of sterile PDA. Inoculated plants were kept at 27°C for 5 weeks. Similar symptoms developed on the inoculated plants within 4 weeks after inoculation. P. palmivora was consistently reisolated from symptomatic plants. No symptoms developed on control plants. P. palmivora attacks a wide range of crop species including lavenders (1,2,4). To our knowledge, this is the first report of a root rot caused by P. palmivora, a new pathogen of lavender in Turkey. References: (1) S. Davino et al. Plant Dis. 86:561, 2002. (2) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St Paul, MN, 1996. (3) D. J. Stamps. C.M.I. Descr. Fungi Bact. 831:1, 1985. (4) G. A. Torres et al. Plant Dis. 94:1163, 2010.


An empirical case study examining effectiveness of environmental enrichment in two captive Australian Sea Lions (Neophoca cinerea).
This case study examined the effect of environmental enrichment on the activity budgets of a male and female Australian Sea Lion (Neophoca cinerea) housed together at Adelaide Zoo. Using non-food-related (intrinsic) and food-related (extrinsic) enrichment objects, the study conducted an ABABA (withdrawal) experimental design over a 30-day period (180 hr). The study expected extrinsically reinforcing objects to be more effective than intrinsically reinforcing objects in reducing pattern swimming. The male sea lion spent more than 45% of scans engaged in pattern swimming during the initial baseline, which was reduced by at least 25% when enrichment items were present. However, there was no evidence of stereotypic behavior in the female sea lion, indicating that individual differences may exist. When enrichment was present, the study observed more active behaviors in both nonhuman animals. They spent more time interacting with the non-food-related objects overall. Therefore, introducing simple enrichment devices offers a cheap, practical, and effective method of adding complexity to the environment, which is likely to benefit the animals' welfare and enhance the zoo-visitor experience.


Expression of the adhesion molecules ICAM-1, VCAM-1, LFA-1 and VLA-4 in the skin is modulated in progressing stages of chronic venous insufficiency.
In inflammation and wound healing, dynamic changes in cell adhesion and migration are fundamental properties of the cells involved. Disturbed interaction of leukocytes with microvascular endothelial cells has been proposed to be a central pathogenic factor in chronic venous insufficiency. This disease may therefore serve to elucidate dysregulated modulation of adhesion molecule expression in conditions of chronic inflammation and impaired wound healing. In this study, we determined how the expression of ICAM-1/VCAM-1 on endothelial cells and their ligands LFA-1/VLA-4 on leukocytes is modulated in skin of progressing stages of chronic venous insufficiency. Immunohistochemical staining of skin biopsies revealed an increase in the expression of ICAM-1 and VCAM-1 on endothelial cells in an early stage of venous disease such as stasis dermatitis. Such protein expression correlated with an increase of corresponding mRNA in skin biopsies. Expression of these CAMs on endothelial cells was accompanied by the occurrence of a marked perivascular infiltration of leukocytes, which expressed increased levels of LFA-1 and VLA-4. In progressing stages of chronic venous insufficiency, characterized by hyperpigmentation and lipodermatosclerosis, which precede skin ulceration, all these CAMs remained upregulated on endothelial cells and infiltrating leukocytes. Our findings indicate that following an initial peak expression during stasis dermatitis, vascular ICAM-1 and VCAM-1 expression is not downmodulated to baseline levels, but remains upregulated. This possibly promotes tissue damage by a perpetuated, upregulated influx of activated leukocytes, finally leading to skin ulceration.


Electromagnetic Versus Blind Guidance of a Postpyloric Feeding Tube in Critically Ill Children.
Postpyloric feeding tube placement is a time-consuming procedure associated with multiple attempts and radiation exposure. Our objective with this study is to compare the time, attempts, and radiation exposure using the electromagnetic versus blind method to place a postpyloric feeding tube in critically ill children. Our hypothesis is that using electromagnetic guidance decreases the procedure time, number of x-rays, and number of attempts, compared to the blind method. Eleven pediatric nurses participated in a randomized controlled intention-to-treat study at an academic pediatric medical, surgical, and congenital cardiac ICU. University of Texas Health Epidemiology and Biostatistics generated a randomization sequence with sealed envelopes. A standard (2-sided) F-test of association between the electromagnetic and blind method yielded 40 subjects with 86% power. Data were analyzed with Fisher's exact test for categorical variables and the Wilcoxon rank test for continuous variables, with data documented as median (interquartile range [IQR]). We randomly assigned 52 patients to either the electromagnetic (n = 28) or blind method (n = 24). The number of attempts and radiographs was at a median of 2 (IQR: 1-2.25) using the blind method, compared to the electromagnetic method at a median of 1 (IQR: 1.0-1.0; P = .001). Successful guidance was 96.4% with the electromagnetic method, compared to only 66.7% with the blind technique (P = .008). The total time required was 2.5 minutes (IQR: 2.0-7.25) with the electromagnetic method, compared to 19 minutes (IQR: 9.25-27.0) for the blind method (P = .001). Electromagnetic guidance is a superior, faster, and overall safer method to place a postpyloric feeding tube in critically ill children.


Understanding The Relationships Between Noncommunicable Diseases, Unhealthy Lifestyles, And Country Wealth.
The amount of international aid given to address noncommunicable diseases is minimal. Most of it is directed to wealthier countries and focuses on the prevention of unhealthy lifestyles. Explanations for the current direction of noncommunicable disease aid include that these are diseases of affluence that benefit from substantial research and development into their treatment in high-income countries and are better addressed through domestic tax and policy measures to reduce risk-factor prevalence than through aid programs. This study assessed these justifications. First, we examined the relationships among premature adult mortality, defined as the probability that a person who has lived to the age of fifteen will die before the age of sixty from noncommunicable diseases; the major risk factors for these diseases; and country wealth. Second, we compared noncommunicable and communicable diseases prevalent in poor and wealthy countries alike, and their respective links to economic development. Last, we examined the respective roles that wealth and risk prevention have played in countries that achieved substantial reductions in premature mortality from noncommunicable diseases. Our results support greater investment in cost-effective noncommunicable disease preventive care and treatment in poorer countries and a higher priority for reducing key risk factors, particularly tobacco use.


Surveillance and intervention studies on respiratory cancers in asbestos-exposed workers.
A systematic review of the literature on the surveillance of workers at presumed increased risk for respiratory cancer because of their exposure to asbestos revealed surveillance programs at the national, population, industrial, and factory (workplace) levels. Furthermore, 3 randomized chemoprevention trials involving workers exposed to asbestos were found. The nationwide programs to survey problems related to occupational exposure to asbestos were conducted in Europe. Some of the countries have policies for the surveillance of workers exposed either currently or formerly to asbestos. The results of the chemoprevention trials suggest that there are, as yet, no practical tools for efficient, safe chemoprevention of asbestos-induced respiratory malignancies.


The impact of sex education mandates on teenage pregnancy: International evidence.
To date most studies of the impact of school-based sex education have focused either on specific, local interventions or experiences at a national level. In this paper, we use a new cross-country dataset to explore the extent to which laws on sex education affect teenage pregnancy rates in developed countries. We find some evidence that laws mandating sex education in schools are associated with higher rates of teenage fertility. Parental opt out laws may minimise adverse effects of sex education mandates for younger teens. The estimated effects of mandatory sex education are robust to some but not all of our specifications designed to tease out causality. Taken together, changes in national laws relating to sexual health are unable to explain the significant declines in teenage pregnancy rates, which have been observed in many developed countries in recent years.


Cost of the Diet (CoD) tool: first results from Indonesia and applications for policy discussion on food and nutrition security.
The Minimum Cost of a Nutritious Diet (MCNut) is the cost of a theoretical diet satisfying all nutrient requirements of a family at the lowest possible cost, based on availability, price, and nutrient content of local foods. A comparison with household expenditure shows the proportion of households that would be able to afford a nutritious diet. To explore using the Cost of Diet (CoD) tool for policy dialogue on food and nutrition security in Indonesia. From October 2011 to June 2012, market surveys collected data on food commodity availability and pricing in four provinces. Household composition and expenditure data were obtained from secondary data (SUSENAS 2010). Focus group discussions were conducted to better understand food consumption practices. Different types of fortified foods and distribution mechanisms were also modeled. Stark differences were found among the four areas: in Timor Tengah Selatan, only 25% of households could afford to meet the nutrient requirements, whereas in urban Surabaya, 80% could. The prevalence rates of underweight and stunting among children under 5 years of age in the four areas were inversely correlated with the proportion of households that could afford a nutritious diet. The highest reduction in the cost of the child's diet was achieved by modeling provision of fortified blended food through Social Safety Nets. Rice fortification, subsidized or at commercial price, can greatly improve nutrient affordability for households. The CoD analysis is a useful entry point for discussions on constraints on achieving adequate nutrition in different areas and on possible ways to improve nutrition, including the use of special foods and different distribution strategies.


Machine Learning in Medical Imaging.
Advances in both imaging and computers have synergistically led to a rapid rise in the potential use of artificial intelligence in various radiological imaging tasks, such as risk assessment, detection, diagnosis, prognosis, and therapy response, as well as in multi-omics disease discovery. A brief overview of the field is given here, allowing the reader to recognize the terminology, the various subfields, and components of machine learning, as well as the clinical potential. Radiomics, an expansion of computer-aided diagnosis, has been defined as the conversion of images to minable data. The ultimate benefit of quantitative radiomics is to (1) yield predictive image-based phenotypes of disease for precision medicine or (2) yield quantitative image-based phenotypes for data mining with other -omics for discovery (ie, imaging genomics). For deep learning in radiology to succeed, note that well-annotated large data sets are needed since deep networks are complex, computer software and hardware are evolving constantly, and subtle differences in disease states are more difficult to perceive than differences in everyday objects. In the future, machine learning in radiology is expected to have a substantial clinical impact with imaging examinations being routinely obtained in clinical practice, providing an opportunity to improve decision support in medical image interpretation. The term of note is decision support, indicating that computers will augment human decision making, making it more effective and efficient. The clinical impact of having computers in the routine clinical practice may allow radiologists to further integrate their knowledge with their clinical colleagues in other medical specialties and allow for precision medicine.


Glymphatic fluid transport controls paravascular clearance of AAV vectors from the brain.
Adeno-associated viruses (AAV) are currently being evaluated in clinical trials for gene therapy of CNS disorders. However, host factors that influence the spread, clearance, and transduction efficiency of AAV vectors in the brain are not well understood. Recent studies have demonstrated that fluid flow mediated by aquaporin-4 (AQP4) channels located on astroglial end feet is essential for exchange of solutes between interstitial and cerebrospinal fluid. This phenomenon, which is essential for interstitial clearance of solutes from the CNS, has been termed glial-associated lymphatic transport or glymphatic transport. In the current study, we demonstrate that glymphatic transport profoundly affects various aspects of AAV gene transfer in the CNS. Altered localization of AQP4 in aged mouse brains correlated with significantly increased retention of AAV vectors in the parenchyma and reduced systemic leakage following ventricular administration. We observed a similar increase in AAV retention and transgene expression upon i.c.v. administration in AQP4-/- mice. Consistent with this observation, fluorophore-labeled AAV vectors showed markedly reduced flux from the ventricles of AQP4-/- mice compared with WT mice. These results were further corroborated by reduced AAV clearance from the AQP4-null brain, as demonstrated by reduced transgene expression and vector genome accumulation in systemic organs. We postulate that deregulation of glymphatic transport in aged and diseased brains could markedly affect the parenchymal spread, clearance, and gene transfer efficiency of AAV vectors. Assessment of biomarkers that report the kinetics of CSF flux in prospective gene therapy patients might inform variable treatment outcomes and guide future clinical trial design.


Clinically detectable nerve fiber atrophy precedes the onset of glaucomatous field loss.
Standardized perimetry and nerve fiber layer and color fundus photography were performed annually on 1344 eyes with elevated intraocular pressures. In 83 eyes, glaucomatous field defects developed that met rigid criteria on manual kinetic and suprathreshold static perimetry. Individual nerve fiber layer photographs were read by two masked observers. The more sensitive of the two identified nerve fiber layer defects in 88% of readable photographs at the time field loss first occurred; 60% (6/10) of eyes already had nerve fiber layer defects 6 years before field loss. In contrast, the nerve fiber layer was considered abnormal in only 11% (3/27) of normal eyes and 26% (84/327) of hypertensive eyes. The location of nerve fiber layer and field defects closely corresponded, but nerve fiber layer loss was generally more widespread. Examiner experience and severity of optic nerve damage influenced results. Mild focal defects were more readily recognized than more severe diffuse atrophy. Nerve fiber layer defects expanded with time, often by the development and coalescence of adjacent areas of damage.


The effect of sucrase-isomaltase deficiency on metabolism, food intake and preferences: protocol for a dietary intervention study.
In Greenland, traditional marine foods are increasingly being replaced by sucrose- and starch-rich foods. A knock-out c.273_274delAG variant in the sucrase-isomaltase (SI) gene is relatively common in Greenland, with homozygous carriers being unable to digest sucrose and some starch. The variant is associated with a healthier metabolic phenotype in Greenlanders, which is confirmed by SI-knockout mice. We aim to assess if the healthy phenotype is explained by metabolic and microbial differences and if food and taste preferences differ between SI-genotypes. This paper describes the protocol for a randomised cross-over trial conducted in Greenland in 2022 with two dietary interventions of three days; a traditional meat- and fish-rich diet and a starch-rich Western diet with 11 energy% sucrose. The power calculation showed that 22 homozygous SI-carriers and 22 non-carriers were sufficient to detect a 0.5 mmol/L difference in glycaemic variability (80% power, α=0.05). We enrolled 18 carriers and 20 non-carriers. We examined food preferences at baseline and collected samples before and after each intervention for metabolic, metabolome, and microbiome profiling. Analyses of samples have not been completed yet. The Ethics Committee of Greenland approved the study. Results will be disseminated in international peer-reviewed journals and to the general Greenlandic population. NCT05375656.


Microorganism mediated reproductive isolation in flour beetles (genus Tribolium).
Reproductive isolation is induced by microorganisms in diverse geographic strains of the flour beetle Tribolium confusum (Coleoptera:Tenebrionidae). The incompatibility between populations is due to nongenetic cytoplasmically inherited factors. Males of infected strains produce no progeny when crossed with females of noninfected strains; however, they produce "normal" numbers of progeny when crossed with infected females. Males from noninfected strains show no reproductive isolation. Infected strains of T. confusum can be cured when tetracycline or other antibiotics are added to the flour medium. "Cured" strains become partially reproductively isolated from all noncured strains including the source strain


Efficacy of a non-drinking mental simulation intervention for reducing student alcohol consumption.
To assess the impact of a mental simulation intervention designed to reduce student alcohol consumption by asking participants to imagine potential positive outcomes of and/or strategic processes involved in not drinking during social occasions. English university students aged 18-25 years (n = 211, Mage = 20 years) were randomly allocated to one of four intervention conditions. The dependent variables were weekly alcohol consumption, heavy episodic drinking (HED) frequency and frequency of social occasions at which participants did not drink alcohol when others were drinking alcohol ('episodic non-drinking'). Measures of alcohol-related prototypes (i.e., prototypical non-drinker, prototypical regular drinker) were used to compute sociability prototype difference scores as a potential mediator of any intervention effects. All measures were taken at baseline and at 2- and 4-week follow-up. Participants completed one of four exercises involving either imagining positive outcomes of non-drinking during a social occasion (outcome condition); imagining strategies required for non-drinking during a social occasion (process condition); imagining both positive outcomes and required strategies (combined condition); or completing a drinks diary task (control condition). Latent growth curve analyses revealed a more substantial rate of decrease in weekly unit consumption and HED frequency among outcome condition and process condition participants, relative to control condition participants. Non-significant differences were found between the combined condition and the control condition. Across the whole sample, an inverted U-shape trend indicated an initial increase in episodic non-drinking before it returned to baseline levels. This study provides preliminary evidence that mental simulation interventions focused on non-drinking can successfully promote behaviour change. Statement of contribution What is already known on this subject? UK drinking recommendations advise two 'dry days' per week (NHS, 2014). Benefits of, and strategies involved in, social non-drinking exist (Conroy & de Visser, 2014). Mental simulation interventions may help reduce student drinking (Hagger, Lonsdale, & Chatzisarantis, 2012; Hagger, Lonsdale, Koka et al., 2012). What does this study add? Demonstrates efficacy of a novel 'non-drinking' mental simulation exercise. Suggests that healthier alcohol prototypes can be encouraged via a health promotion intervention. Shows potential utility of 'episodic non-drinking' as an indicator of health-adherent drinking.


Does shortening the pitch make junior cricketers bowl better?
In order to get bounce and movement seam bowlers need to bowl the ball "into" the pitch. Standard deliveries by elite players are typically projected at around 7° below horizontal. In contrast, young players currently often need to release the ball almost horizontally in an effort to get the ball to bounce close enough to the batter. We anticipated that shortening the pitch could be a simple way to help young bowlers to release the ball at a better angle and with more consistency. Twenty county or best in club age group under 10 and under 11 seam bowlers were analysed bowling indoors on two different pitch lengths. They were found to project the ball on average 3.4° further below horizontal on a 16 yard pitch compared with a 19 yard pitch, while ball speed and position at release changed negligibly. Pitch length did not affect the consistency of the release parameters. The shorter pitch led to a ball release angle closer to that of elite bowlers without changing release speed, and this should enable players to achieve greater success and develop more variety in their bowling.


Continuity of mammalian fauna over the last 200,000 y in the Indian subcontinent.
Mammalian extinction worldwide during the Late Pleistocene has been a major focus for Quaternary biochronology and paleoecology. These extinctions have been variably attributed to the impacts of climate change and human interference. However, until relatively recently, research has been largely restricted to the Americas, Europe, and Australasia. We present the oldest Middle-Late Pleistocene stratified and numerically dated faunal succession for the Indian subcontinent from the Billasurgam cave complex. Our data demonstrate continuity of 20 of 21 identified mammalian taxa from at least 100,000 y ago to the present, and in some cases up to 200,000 y ago. Comparison of this fossil record to contemporary faunal ranges indicates some geographical redistribution of mammalian taxa within India. We suggest that, although local extirpations occurred, the majority of taxa survived or adapted to substantial ecological pressures in fragmented habitats. Comparison of the Indian record with faunal records from Southeast and Southwest Asia demonstrates the importance of interconnected mosaic habitats to long-term faunal persistence across the Asian tropics. The data presented here have implications for mammalian conservation in India today, where increasing ecological circumscription may leave certain taxa increasingly endangered in the most densely populated region of the world.


Identification of protein-protein interactions of isoflavonoid biosynthetic enzymes with 2-hydroxyisoflavanone synthase in soybean (Glycine max (L.) Merr.).
Metabolic enzymes, including those involved in flavonoid biosynthesis, are proposed to form weakly bound, ordered protein complexes, called "metabolons". Some hypothetical models of flavonoid biosynthetic metabolons have been proposed, in which metabolic enzymes are believed to anchor to the cytoplasmic surface of the endoplasmic reticulum (ER) via ER-bound cytochrome P450 isozymes (P450s). However, no convincing evidence for the interaction of flavonoid biosynthetic enzymes with P450s has been reported previously. Here, we analyzed binary protein-protein interactions of 2-hydroxyisoflavanone synthase 1 (GmIFS1), a P450 (CYP93C), with cytoplasmic enzymes involved in isoflavone biosynthesis in soybean. We identified binary interactions between GmIFS1 and chalcone synthase 1 (GmCHS1) and between GmIFS1 and chalcone isomerases (GmCHIs) by using a split-ubiquitin membrane yeast two-hybrid system. These binary interactions were confirmed in planta by means of bimolecular fluorescence complementation (BiFC) using tobacco leaf cells. In these BiFC analyses, fluorescence signals that arose from the interaction of these cytoplasmic enzymes with GmIFS1 generated sharp, network-like intracellular patterns, which was very similar to the ER-localized fluorescence patterns of GmIFS1 labeled with a fluorescent protein. These observations provide strong evidence that, in planta, interaction of GmCHS1 and GmCHIs with GmIFS1 takes place on ER on which GmIFS1 is located, and also provide important clues to understand how enzymes and proteins form metabolons to establish efficient metabolic flux of (iso)flavonoid biosynthesis.


Evolution of the ferric reductase domain (FRD) superfamily: modularity, functional diversification, and signature motifs.
A heme-containing transmembrane ferric reductase domain (FRD) is found in bacterial and eukaryotic protein families, including ferric reductases (FRE), and NADPH oxidases (NOX). The aim of this study was to understand the phylogeny of the FRD superfamily. Bacteria contain FRD proteins consisting only of the ferric reductase domain, such as YedZ and short bFRE proteins. Full length FRE and NOX enzymes are mostly found in eukaryotic cells and all possess a dehydrogenase domain, allowing them to catalyze electron transfer from cytosolic NADPH to extracellular metal ions (FRE) or oxygen (NOX). Metazoa possess YedZ-related STEAP proteins, possibly derived from bacteria through horizontal gene transfer. Phylogenetic analyses suggests that FRE enzymes appeared early in evolution, followed by a transition towards EF-hand containing NOX enzymes (NOX5- and DUOX-like). An ancestral gene of the NOX(1-4) family probably lost the EF-hands and new regulatory mechanisms of increasing complexity evolved in this clade. Two signature motifs were identified: NOX enzymes are distinguished from FRE enzymes through a four amino acid motif spanning from transmembrane domain 3 (TM3) to TM4, and YedZ/STEAP proteins are identified by the replacement of the first canonical heme-spanning histidine by a highly conserved arginine. The FRD superfamily most likely originated in bacteria.


FeatureExtract--extraction of sequence annotation made easy.
Work on a large number of biological problems benefits tremendously from having an easy way to access the annotation of DNA sequence features, such as intron/exon structure, the contents of promoter regions and the location of other genes in upsteam and downstream regions. For example, taking the placement of introns within a gene into account can help in a phylogenetic analysis of homologous genes. Designing experiments for investigating UTR regions using PCR or DNA microarrays require knowledge of known elements in UTR regions and the positions and strandness of other genes nearby on the chromosome. A wealth of such information is already known and documented in databases such as GenBank and the NCBI Human Genome builds. However, it usually requires significant bioinformatics skills and intimate knowledge of the data format to access this information. Presented here is a highly flexible and easy-to-use tool for extracting feature annotation from GenBank entries. The tool is also useful for extracting datasets corresponding to a particular feature (e.g. promoters). Most importantly, the output data format is highly consistent, easy to handle for the user and easy to parse computationally. The FeatureExtract web server is freely available for both academic and commercial use at http://www.cbs.dtu.dk/services/FeatureExtract/.


Magnetic Resonance Imaging Based Flow Field and Lagrangian Particle Tracking From a Left Ventricular Assist Device.
This study explores the optimal left ventricular assist device (LVAD) cannula outflow configuration in a patient-specific replica of the aorta. The volumetric velocity field is measured using phase-contrast magnetic resonance imaging (PC-MRI) under a physiologically relevant steady flow. The effect of the LVAD outflow graft insertion site and anastomosis angle on the transport of embolic particles to cranial vessels is studied by solving the particle equation of motion for spheres in the range of 0.1-1.0 mm using the measured three-dimensional (3D) velocity field. Results show that for a given aorta anatomy, it is possible to design the cannula graft location and terminal curvature so that the probability of embolic transport to the cranial vessels is significantly minimized. This is particularly important since the complex flow pattern in each cannula case affects the embolic trajectories differently, and hence the common assumption that particles distribute by the volumetric flow division does not hold.


Embracing and resisting climate identities in the Australian press: Sceptics, scientists and politics.
This article charts the development of a label that appeared early on in Australian debates on climate change, namely 'greenhouse sceptics'. We explore who uses the label, for what purposes and with which effects, and how this label may contribute to the development of social representations in the climate debate. Our findings show that over the last 25 years, 'greenhouse sceptic' has been used by journalists and climate scientists to negativize those criticizing mainstream climate science, but that it has also been used, even embraced, by Australian climate sceptics to label themselves in order to construct a positive identity modelled on celebrity sceptics in the United States. We found that the label was grounded in religious metaphors that frame mainstream science as a catastrophist and alarmist religious cult. Overall, this article provides detailed insights into the genealogy of climate scepticism in a particular cultural and historical context.


Endothelial connexins in vascular function.
Gap junctions are essential for intercellular crosstalk in blood and lymphatic vasculature. These clusters of intercellular channels ensure direct communication among endothelial cells and between endothelial and smooth muscle cells, and the synchronization of their behavior along the vascular tree. Gap junction channels are formed by connexins; six connexins form a connexon or hemichannel and the docking of two connexons result in a full gap junction channel allowing for the exchange of ions and small metabolites between neighboring cells. Recent evidence indicates that the intracellular domains of connexins may also function as an interaction platform (interactome) for other proteins, thereby regulating their function. Interestingly, fragments of Cx proteins generated by alternative internal translation were recently described, although their functions in the vascular wall remain to be uncovered. Variations in connexin expression are observed along different types of blood and lymphatic vessels; the most commonly found endothelial connexins are Cx37, Cx40, Cx43 and Cx47. Physiological studies on connexin-knockout mice demonstrated the essential roles of these channel-forming proteins in the coordination of vasomotor activity, endothelial permeability and inflammation, angiogenesis and in the maintenance of fluid balance in the body.


Elimination of the immunogenicity of therapeutic antibodies.
The immunogenicity of therapeutic Abs limits their long-term use. The processes of complementarity-determining region grafting, resurfacing, and hyperchimerization diminish mAb immunogenicity by reducing the number of foreign residues. However, this does not prevent anti-idiotypic and anti-allotypic responses following repeated administration of cell-binding Abs. Classical studies have demonstrated that monomeric human IgG is profoundly tolerogenic in a number of species. If cell-binding Abs could be converted into monomeric non-cell-binding tolerogens, then it should be possible to pretolerize patients to the therapeutic cell-binding form. We demonstrate that non-cell-binding minimal mutants of the anti-CD52 Ab CAMPATH-1H lose immunogenicity and can tolerize to the "wild-type" Ab in CD52-expressing transgenic mice. This finding could have utility in the long-term administration of therapeutic proteins to humans.


Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions.
This study addressed the prevalences, correlates, co-morbidity and disability of DSM-IV generalized anxiety disorder (GAD) and other psychiatric disorders in a large national survey of the general population, the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). The study presents nationally representative data, for the first time, on prevalence, correlates, co-morbidity, and comparative disability of DSM-IV GAD. Data are taken from a large (n=43093) representative sample of the adult USA population.R: Prevalences of 12-month and lifetime GAD were 2.1% and 4.1%. Being female, middle-aged, widowed/separated/divorced, and low income increased risk, while being Asian, Hispanic, or Black decreased risk. GAD was highly co-morbid with substance use, and other anxiety, mood, and personality disorders. Co-morbidity in GAD was not substantially greater than for most other Axis I and II disorders. Disability and impairment in pure GAD were equivalent to pure mood disorders, but significantly greater than in pure substance use, and other anxiety and personality disorders. Individuals co-morbid for GAD and each mood disorder were more disabled than those with pure forms of GAD or each mood disorder. When co-morbid with GAD, nicotine dependence and other anxiety and personality disorders were not associated with increased disability over that associated with pure GAD, but GAD did show increased disability over that due to each of these disorders in pure form.Conclusions. Associations between GAD and Axis I and II disorders were strong and significant, with variation among specific disorders. Results strongly support GAD as an independent disorder with significant impairment and disability.


Study of the impact on Salmonella of moving outdoor pigs to fresh land.
Anecdotal evidence has suggested that outdoor-kept pigs show an improvement to health and productivity after being moved to a new site. This study explores whether Salmonella occurrence reduced and was sustained after moving to a new site. Nine farms were followed for a year in which four sampling visits were completed. The highest detection of Salmonella was from pooled faecal dropping from pigs, run-off/ pooled water, rodents and wild birds. Descriptive summaries showed that the prevalence of both all Salmonella and serovars of public health importance were lower at all visits after the move. Some variability was shown in results from individual farms, but a year after the move, six farms still maintained a lower prevalence. A risk factor model showed that the prevalence at visits 2 and 3 after the move was significantly lower than baseline, after accounting for a number of significant factors that were included in the model. These were sample type and seasonality (included as a priori), presence of coughing in the sampled group and Glasser's disease on the farm, and the use of tent or kennel accommodation. This finding provides important evidence that more frequent site moves may help reduce Salmonella prevalence in outdoor herds.


Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide.
The presurface (preS) proteins of hepatitis B virus are structural components of the viral envelope that may play important roles in virion assembly and infectivity. They are specified by a large open reading frame that includes the coding region for the major surface (S) protein in its 3' half. Translation of the preS proteins initiates upstream from the S region, giving rise to proteins that are composed of the S domain and an additional 163 (preS1) or 55 (preS2) amino acids. Little is known about the biosynthesis and assembly of these proteins. The expression of the S and preS1 proteins was examined by transfecting cultured mammalian cells with viral DNA and injecting synthetic messenger RNA's into Xenopus oocytes. In contrast to the proteins encoded by the S region, the preS1 proteins are not detectably secreted into the culture medium. Furthermore, when the S and preS1 proteins are synthesized together, secretion of the S proteins is specifically and strongly inhibited. The results suggest a unique molecular interaction during secretion of the S and preS proteins that may be important for virus assembly.


GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon.
Short-chain fatty acids, generated in colon by bacterial fermentation of dietary fiber, protect against colorectal cancer and inflammatory bowel disease. Among these bacterial metabolites, butyrate is biologically most relevant. GPR109A is a G-protein-coupled receptor for nicotinate but recognizes butyrate with low affinity. Millimolar concentrations of butyrate are needed to activate the receptor. Although concentrations of butyrate in colonic lumen are sufficient to activate the receptor maximally, there have been no reports on the expression/function of GPR109A in this tissue. Here we show that GPR109A is expressed in the lumen-facing apical membrane of colonic and intestinal epithelial cells and that the receptor recognizes butyrate as a ligand. The expression of GPR109A is silenced in colon cancer in humans, in a mouse model of intestinal/colon cancer, and in colon cancer cell lines. The tumor-associated silencing of GPR109A involves DNA methylation directly or indirectly. Reexpression of GPR109A in colon cancer cells induces apoptosis, but only in the presence of its ligands butyrate and nicotinate. Butyrate is an inhibitor of histone deacetylases, but apoptosis induced by activation of GPR109A with its ligands in colon cancer cells does not involve inhibition of histone deacetylation. The primary changes in this apoptotic process include down-regulation of Bcl-2, Bcl-xL, and cyclin D1 and up-regulation of death receptor pathway. In addition, GPR109A/butyrate suppresses nuclear factor-kappaB activation in normal and cancer colon cell lines as well as in normal mouse colon. These studies show that GPR109A mediates the tumor-suppressive effects of the bacterial fermentation product butyrate in colon.


Biomembrane Fabrication by the Solvent-assisted Lipid Bilayer (SALB) Method.
In order to mimic cell membranes, the supported lipid bilayer (SLB) is an attractive platform which enables in vitro investigation of membrane-related processes while conferring biocompatibility and biofunctionality to solid substrates. The spontaneous adsorption and rupture of phospholipid vesicles is the most commonly used method to form SLBs. However, under physiological conditions, vesicle fusion (VF) is limited to only a subset of lipid compositions and solid supports. Here, we describe a one-step general procedure called the solvent-assisted lipid bilayer (SALB) formation method in order to form SLBs which does not require vesicles. The SALB method involves the deposition of lipid molecules onto a solid surface in the presence of water-miscible organic solvents (e.g., isopropanol) and subsequent solvent-exchange with aqueous buffer solution in order to trigger SLB formation. The continuous solvent exchange step enables application of the method in a flow-through configuration suitable for monitoring bilayer formation and subsequent alterations using a wide range of surface-sensitive biosensors. The SALB method can be used to fabricate SLBs on a wide range of hydrophilic solid surfaces, including those which are intractable to vesicle fusion. In addition, it enables fabrication of SLBs composed of lipid compositions which cannot be prepared using the vesicle fusion method. Herein, we compare results obtained with the SALB and conventional vesicle fusion methods on two illustrative hydrophilic surfaces, silicon dioxide and gold. To optimize the experimental conditions for preparation of high quality bilayers prepared via the SALB method, the effect of various parameters, including the type of organic solvent in the deposition step, the rate of solvent exchange, and the lipid concentration is discussed along with troubleshooting tips. Formation of supported membranes containing high fractions of cholesterol is also demonstrated with the SALB method, highlighting the technical capabilities of the SALB technique for a wide range of membrane configurations.


Lymphangioleiomyomatosis of the uterus simulating high-stage endometrial stromal sarcoma.
Symptomatic uterine lymphangioleiomyomatosis (LAM) simulating high-stage uterine sarcoma in a patient with tuberous sclerosis complex is reported. A 49-year-old female presented with abdominal pain and anemia. Preoperative workup revealed a uterine mass and a large amount of peritoneal free fluid and possible metastatic implant along the lateral edge of the liver. The patient also had a large right pleural effusion. A fungating anterior uterine fundal mass with apparent perforation and intraabdominal hemorrhage was found on laparotomy. A portion of the mass was excised and initially interpreted as an endometrial stromal sarcoma. Microscopic examination revealed multiple vascular epithelioid smooth muscle proliferations in the uterus and serosal surface of the fallopian tube and periaortic lymph node lymphangioleiomyomas. The uterine, fallopian tube, and nodal lesions were positive for smooth muscle actin, desmin, and HMB-45, findings characteristic of LAM. Additional examination of the patient revealed stigmata of tuberous sclerosis complex. Although uterine LAM is uncommon, it may be associated with pelvic and/or abdominal symptoms and may simulate a primary uterine mesenchymal neoplasm.


Classics in Chemical Neuroscience: Xanomeline.
Xanomeline (1) is an orthosteric muscarinic acetylcholine receptor (mAChR) agonist, often referred to as M1/M4-preferring, that received widespread attention for its clinical efficacy in schizophrenia and Alzheimer's disease (AD) patients. Despite the compound's promising initial clinical results, dose-limiting side effects limited further clinical development. While xanomeline, and related orthosteric muscarinic agonists, have yet to receive approval from the FDA for the treatment of these CNS disorders, interest in the compound's unique M1/M4-preferring mechanism of action is ongoing in the field of chemical neuroscience. Specifically, the promising cognitive and behavioral effects of xanomeline in both schizophrenia and AD have spurred a renewed interest in the development of safer muscarinic ligands with improved subtype selectivity for either M1 or M4. This Review will address xanomeline's overall importance in the field of neuroscience, with a specific focus on its chemical structure and synthesis, pharmacology, drug metabolism and pharmacokinetics (DMPK), and adverse effects.


Analysis of resected gastric cancer in Turkish population.
Gastric cancer is still an important health issue in Eastern Europe and Middle East, including Turkey, although its prevalence is decreasing in the western world. In order to define the profiles of the patients operated with a diagnosis of gastric cancer in Turkey, a multicenter retrospective study was conducted. Six hundred and forty-eight of the 840 patients with complete data in all parameters were included in the analysis. The median follow-up time was 17.16 months (range, 6-143.63 months). Mean age was 57±11.7 (19-85). There was a recurrent disease in 42% of the tumors located at cardia, corpus or antrum, and 86% of diffuse tumors (p<0.0001). The ratio of patients with recurrent disease was greater in stage III and IV tumors (52%) than stage II (29%) and stage I (17%) tumors. There were also greater recurrence ratios in patients with node positive (pN1-3) patients than pN0 tumors, and pT3-4 tumors than pT1 or pT2 tumors. Any recurrence was found in 48% of the tumors with lymphovascular invasion, while in 39% without lymphovascular invasion (p=0.026). A statistically significant difference was found in the recurrence status of patients with positive / dissected node ratio of <10% and ≥10% (p<0.0001). Gastric cancer cases in Turkey are seen at a younger age, and at a higher stage. Proximal gastric cancer is seen much less than the western series. Prognostic significance of lymphovascular invasion in both univariate, and multivariate analyses is noteworthy.


Failure of postural manoeuvres to prevent lumbar puncture headache.
Diagnostic lumbar puncture was performed on 76 neurological inpatients. They were randomly allocated to one of four bed rest positions for four hours following the procedure (supine and horizontal, prone and horizontal, supine with head-down tilt and prone with head-down tilt) after which they were allowed to get up. There was no substantial or significant difference in the incidence of headache between the four groups. Expectation of headache did not appear to be an important factor in its development.


Analysis of MDM2 Amplification in 43 Endometrial Stromal Tumors: A Potential Diagnostic Pitfall.
MDM2 amplification is known to occur in a variety of neoplasms and its detection by fluorescence in situ hybridization is helpful in distinguishing well-differentiated and dedifferentated liposarcoma from classic lipoma. We recently evaluated a mesenteric mass initially diagnosed as dedifferentiated liposarcoma, largely due to the neoplasm's myxoid morphology and MDM2 expression by immunohistochemistry, from a 46-yr-old woman with a history of uterine low-grade endometrial stromal sarcoma (LG-ESS) with a JAZF1 rearrangement. Our workup of the mesenteric mass revealed a JAZF1 rearrangement and a revised diagnosis of metastatic LG-ESS with myxoid change was rendered. Retrospective testing of the mesenteric mass was negative for MDM2 amplification, an uncommon, but known diagnostic pitfall in MDM2 expression by immunohistochemistry. As MDM2 amplification is not specific for the diagnosis of liposarcoma, we investigated its occurrence in 43 cases of endometrial stromal tumors: 14 uterine LG-ESS, 11 metastatic or recurrent uterine LG-ESS, 8 undifferentiated uterine sarcomas, 5 endometrial stromal nodules, and 4 high-grade ESS with YHWAE rearrangement. In addition, 40 of the 43 cases had previously undergone fluorescence in situ hybridization analysis of JAZF1, PHF1, and YHWAE. Two of the 43 cases (5%) had MDM2 amplification: one was a uterine LG-ESS (JAZF1 rearrangement) and the other was a undifferentiated uterine sarcoma (polysomy intact JAZF1, PHF1, and YHWAE), both metastatic to the lung. Both cases positive for MDM2 amplification showed MDM2 expression by immunohistochemistry. At last follow-up, both patients had died of disease (19 and 60 mo). Our study is the first to demonstrate MDM2 amplification in endometrial stromal tumor. Awareness of MDM2 amplification in endometrial stromal tumor is critical; particularly in locations more common to liposarcoma, to avoid diagnostic errors.


A single surgeon's experience with the Delaire palatoplasty.
The purpose of this review was to evaluate the clinical outcomes regarding velopharyngeal insufficiency and fistulization in patients with cleft palate who underwent primary repair with the one-stage Delaire palatoplasty. All patients who had a primary Delaire-type palatoplasty performed by the senior surgeon over a 10-year period (1988 to 1998) were studied. During this period, each consecutive patient with an open palatal cleft underwent the same type of repair by the same surgeon. Speech quality and velopharyngeal competence as determined by a single speech pathologist were recorded. A total of 95 patients were included in this series. The average length of follow-up was 31 months (range, 1 to 118 months). Average age at time of surgery was 13.3 months (range, 6 to 180 months). Thirty-one patients (32.6 percent) had significant associated anomalies. The average length of hospital stay was 1.9 days (range, 1 to 8 days) with a trend in recent years toward discharge on postoperative day 1. There were no intraoperative complications, either surgical or anesthetic. Three patients (3.2 percent) developed palatal fistula; none of them required repair. Six patients (6.3 percent) had velopharyngeal incompetence. In patients with more than 1 year of follow-up, the incidence of velopharyngeal incompetence was 9.2 percent (6 of 65). The incidence of fistula after the Delaire palatoplasty was lower than usually reported. The incidence of velopharyngeal incompetence requiring pharyngoplasty was equal to or lower than that seen after other types of palatoplasty, suggesting superior soft-palate muscle function attributable to approximation of the musculus uvulae. The Delaire palatoplasty results in a functional palate with low risk for fistula formation and velopharyngeal incompetence.


Process Evaluation of the BOOST-A™ Transition Planning Program for Adolescents on the Autism Spectrum: A Strengths-Based Approach.
A process evaluation was conducted to determine the effectiveness, usability, and barriers and facilitators related to the Better OutcOmes & Successful Transitions for Autism (BOOST-A™), an online transition planning program. Adolescents on the autism spectrum (n = 33) and their parents (n = 39) provided feedback via an online questionnaire. Of these, 13 participants were interviewed to gain in-depth information about their experiences. Data were analyzed using descriptive statistics and thematic analysis. Four themes were identified: (i) taking action to overcome inertia, (ii) new insights that led to clear plans for the future, (iii) adolescent empowerment through strengths focus, and (iv) having a champion to guide the way. The process evaluation revealed why BOOST-A™ was beneficial to some participants more than others. Trial registration #ACTRN12615000119594.


Isolation and characterization of four medium-size disintegrins from the venoms of Central American viperid snakes of the genera Atropoides, Bothrops, Cerrophidion and Crotalus.
Four disintegrins were isolated from the venoms of the Central American viperid snakes Atropoides mexicanus (atropoimin), Bothrops asper (bothrasperin), Cerrophidion sasai (sasaimin), and Crotalus simus (simusmin). Purifications were performed by reverse-phase HPLC. The four disintegrins have biochemical characteristics, i.e. molecular mass and location of Cys, which allow their classification within the group of medium-size disintegrins. All of them present the canonical RGD sequence, which determines their interaction with integrins in cell membranes. The disintegrins inhibited ADP and collagen-induced human platelet aggregation, with similar IC50s in the nM range. In addition, disintegrins inhibited the adhesion of an endothelial cell line and a melanoma cell line to the extracellular matrix proteins type I collagen, laminin, fibronectin, and vitronectin, albeit showing variable ability to exert this activity. This study expands the inventory of this family of viperid venom proteins, and reports, for the first time, disintegrins from the venoms of species of the genera Atropoides and Cerrophidion.


Immunology and skin in health and disease.
The skin is a complex organ that, in addition to providing a strong barrier against external insults, serves as an arena for a wide variety of inflammatory processes, including immunity against infections, tumor immunity, autoimmunity, and allergy. A variety of cells collaborate to mount functional immune responses, which are initiated by resident populations and evolve through the recruitment of additional cell populations to the skin. Inflammatory responses are quite diverse, resulting in a wide range of signs and symptoms that depend on the initiating signals, characteristics of the infiltrating cell populations, and cytokines that are produced (cytokines are secreted protein that allows for cell-cell communication; usually refers to communication between immune-immune cells or stromal-immune cells). In this work, we will review the skin architecture and resident and recruited cell populations and discuss how these populations contribute to inflammation using human diseases and treatments when possible to illustrate their importance within a clinical context.


Chronic Complications of Diabetes Mellitus: A Mini Review.
Diabetes mellitus (DM) is a major metabolic disorder currently affecting over 350 million people worldwide. Also, another one billion people in the world are pre-diabetic, who may eventually end up with full- blown diabetes. It costs around 1,200 billion USD to diagnose, treat and care for both type 1 DM (T1DM) and type 2 DM (T2DM) patients globally. The disorder is rapidly increasing out of proportion in both developed and developing countries, especially T2DM, which is associated with modern lifestyle habits such as reduced physical activity, diet, obesity and genetic factors. If left untreated, DM can lead to a number of diseases and long-term complications leading subsequently to death. Areas Covered: In this mini review, we aim to highlight a number of complications, cascades or pathways (polyol, hexosamine, protein kinase C, advanced glycation-end product) of events and cellular, sub-cellular and molecular mechanisms associated with DM-induced hyperglycaemia (HG). Chronic complications of DM are caused largely by HG-induced cellular and molecular impairment of neural and vascular structure and function. HG-induced oxidative stress is a major contributor in the development of long-term complications of DM. DM-induced neuropathy and angiopathy, in turn, may lead to the dysfunction of cells, tissues and organ systems.


Testing implementation support for evidence-based programs in community settings: a replication cluster-randomized trial of Getting To Outcomes®.
Community organizations can have difficulty implementing evidence-based prevention programs. More research is needed on implementation support interventions designed to help these organizations implement programs with quality. Preparing to Run Effective Programs (PREP) is a randomized controlled trial testing Getting To Outcomes (GTO), a 2-year implementation support intervention. It compares 15 Boys and Girls Club sites implementing CHOICE (control group), a five-session evidence-based alcohol and drug prevention program, with 14 similar sites implementing CHOICE supported by GTO (intervention group). PREP replicates a previous GTO study that had the same design, but featured a teen pregnancy prevention program instead. All sites received typical CHOICE training. Fourteen intervention sites received GTO manuals, training, and onsite technical assistance to help practitioners complete implementation best practices specified by GTO (i.e., GTO steps). During the first year, technical assistance providers helped the intervention group adopt, plan, and deliver CHOICE. Then, this group was trained on evaluation and quality improvement steps of GTO using feedback reports summarizing their own data, which yielded revised plans for subsequent implementation of CHOICE. This paper presents results regarding GTO's impact on CHOICE fidelity (adherence, quality of delivery, dosage) and the proximal outcomes of the youth participants (aged 10-14)-attitudes and intentions regarding cigarettes, alcohol, and marijuana use. Fidelity was assessed at all sites by observer ratings and attendance logs. Proximal outcomes were assessed via survey at baseline, 3, and 6 months. After 1 year, fidelity and proximal outcomes were similar between Intervention and control groups. After 2 years (which included GTO quality improvement activities that took place between years 1 and 2), intervention sites had higher ratings of CHOICE adherence and quality of delivery (dosage remained similar). Proximal outcomes did not differ between groups in either year, although there was universally high endorsement of prosocial responses to those outcomes from the start. Findings suggest that systematic implementation support provided by GTO can help community organizations achieve better fidelity. Findings replicate the implementation results from a previous GTO study using the same design, but with a different evidence-based program and different fidelity measures. Although proximal outcomes did not change, in large part due to ceiling effects, the implementation findings suggest GTO can support a variety of programs. This project is registered at ClinicalTrials.gov with number NCT02135991 . The trial was first registered on May 12, 2014.


Variation in caesarean section rates in Cyprus, Italy and Iceland: an analysis of the role of the media.
Cyprus has Europe's highest rate of births by caesarean section (CS). In 2015 56% of all babies were born by CS. This compares with 36% in Italy, and 16% in Iceland, which is among the lowest rates in Europe. There is some evidence that CS rates are partly driven by maternal request and media representation. The aim of this review is to explore the depiction of childbirth by CS in the media, and more specifically in newspapers, television, web and informational leaflets in Cyprus, Italy and Iceland. A thematic review of the depiction of CS in the media of Cyprus, Italy and Iceland was carried out through an examination of newspapers, television, web, and informational material published or presented in the included countries in 2017. Materials were identified by searches in PubMed and Google Scholar, using pre-determined key words, inclusion and exclusion criteria, and inclusion was agreed by at least two of the authors. Key themes in each data source were triangulated with each other and between the three countries. The review comprised 81 articles, 10 videos, six birth shows, two informational leaflets and one scientific paper. The central themes were: 1) CS as risky and unnecessary intervention, failure of maternity system; 2) CS as a necessary, life-saving intervention; 3) the ethical dimensions of CS; 4) the changing landscape of childbirth and medicalization; and 5) informed choices. In both Cyprus and Italy, the media focus was on a need to reduce high levels of CS. The focus in Iceland was on normal birth and midwife led care. The differing media messages in the three countries could partly explain the differing CS rates, suggesting that high CS rates are a social phenomenon, rather than a result of clinical need. The media may have a significant influence on the beliefs and choices of maternity service users, their families, and society in general, as well as health professionals and policy makers. Those working in the media have an ethical responsibility to critically examine the impact of high national CS rates, and to report on solutions that could optimize both the safety and the wellbeing of mothers and babies.


Artemisinin induces calcium-dependent protein secretion in the protozoan parasite Toxoplasma gondii.
Intracellular calcium controls several crucial cellular events in apicomplexan parasites, including protein secretion, motility, and invasion into and egress from host cells. The plant compound thapsigargin inhibits the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA), resulting in elevated calcium and induction of protein secretion in Toxoplasma gondii. Artemisinins are natural products that show potent and selective activity against parasites, making them useful for the treatment of malaria. While the mechanism of action is uncertain, previous studies have suggested that artemisinin may inhibit SERCA, thus disrupting calcium homeostasis. We cloned the single-copy gene encoding SERCA in T. gondii (TgSERCA) and demonstrate that the protein localizes to the endoplasmic reticulum in the parasite. In extracellular parasites, TgSERCA partially relocalized to the apical pole, a highly active site for regulated secretion of micronemes. TgSERCA complemented a calcium ATPase-defective yeast mutant, and this activity was inhibited by either thapsigargin or artemisinin. Treatment of T. gondii with artemisinin triggered calcium-dependent secretion of microneme proteins, similar to the SERCA inhibitor thapsigargin. Artemisinin treatment also altered intracellular calcium in parasites by increasing the periodicity of calcium oscillations and inducing recurrent, strong calcium spikes, as imaged using Fluo-4 labeling. Collectively, these results demonstrate that artemisinin perturbs calcium homeostasis in T. gondii, supporting the idea that Ca2+-ATPases are potential drug targets in parasites.


Lower motor neuron involvement in TAR DNA-binding protein of 43 kDa-related frontotemporal lobar degeneration and amyotrophic lateral sclerosis.
TAR DNA-binding protein of 43 kDa (TDP-43) plays a major role in the pathogenesis of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Although a pathological continuity between FTLD and ALS has been suggested, the neuropathological changes of the lower motor neuron (LMN) systems have not been assessed in TDP-43-associated FTLD (FTLD-TDP), to our knowledge. To investigate a pathological continuity between FTLD-TDP and ALS by comparing their respective neuropathological changes in the motor neuron system. A retrospective clinical medical record review and a semiquantitative neuropathological evaluation of the cranial motor nerve nuclei and spinal cord were conducted at autopsy. We included 43 patients with sporadic FTLD-TDP, type A, B, or C, from 269 consecutively autopsied patients with TDP-43 proteinopathy. Patients were categorized as having FTLD without ALS, FTLD-ALS (onset of FTLD symptoms/signs preceded those of ALS), or ALS-FTLD (onset of ALS symptoms/signs preceded those of FTLD). Neuronal TDP-43 pathological changes and neuronal loss. Forty-three patients were included in the clinical analysis, and 29 from whom spinal cords were obtained were included in the neuropathological analysis. Survival time was significantly shorter in the FTLD-ALS and ALS-FTLD groups than in the FTLD without ALS group (P < .001). At neuropathological examination, 89% of patients in the FTLD without ALS group showed aggregations of TDP-43 in the spinal motor neurons. The LMN loss was most severe in ALS-FTLD, followed by FTLD-ALS and FTLD without ALS. All the patients with type A or C FTLD-TDP were included in the FTLD without ALS group, and all those with type B pathological changes were in the FTLD-ALS or the ALS-FTLD group. Lower motor neuron loss and TDP-43-positive skeinlike inclusions were observed in all pathological subtypes. The LMN systems of FTLD-TDP frequently exhibit neuropathological changes corresponding to ALS. Thus, a pathological continuity between FTLD-TDP and ALS is supported at the level of the LMN system.


Attributable inpatient costs of recurrent Clostridium difficile infections.
To determine the attributable inpatient costs of recurrent Clostridium difficile infections (CDIs). Retrospective cohort study. Academic, urban, tertiary care hospital. A total of 3,958 patients aged 18 years or more who developed an initial CDI episode from 2003 through 2009. Data were collected electronically from hospital administrative databases and were supplemented with chart review. Patients with an index CDI episode during the study period were followed up for 180 days from the end of their index hospitalization or the end of their index CDI antibiotic treatment (whichever occurred later). Total hospital costs during the outcome period for patients with recurrent versus a single episode of CDI were analyzed using zero-inflated lognormal models. There were 421 persons with recurrent CDI (recurrence rate, 10.6%). Recurrent CDI case patients were significantly more likely than persons without recurrence to have any hospital costs during the outcome period (P < .001). The estimated attributable cost of recurrent CDI was $11,631 (95% confidence interval, $8,937-$14,588). The attributable costs of recurrent CDI are considerable. Patients with recurrent CDI are significantly more likely to have inpatient hospital costs than patients who do not develop recurrences. Better strategies to predict and prevent CDI recurrences are needed.


Physiologic pineal region, choroid plexus, and dural calcifications in the first decade of life.
Calcifications of the pineal, habenula, choroid plexus, and dura are often physiologic. In the modern CT era with thin-section images and multiplanar reformats, intracranial calcifications have become more conspicuous. We aimed to discover the CT prevalence of pineal region, choroid plexus, and dural calcifications in the first decade of life. Five hundred head CTs from different patients (age range, 0-9 years) encountered during a consecutive 6-month period at a single academic children's hospital were reviewed retrospectively after excluding examinations with artifacts and pineal region masses/hemorrhage. All studies were performed on a 320-detector CT, with 0.5-mm collimation and a 512 × 512 matrix. Five-millimeter reformatted axial, sagittal, and coronal images were analyzed for location and extent of intracranial calcifications. The mean age was 3.5 ± 5.7 years (range, 0-9 years). There were 285 males (57%) and 215 females (43%). Pineal calcifications were present in 5% (n = 25; age range, 3.2-8.9 years; median, 7 years). Habenular calcifications were found in 10% (n = 50; age range, 2.8-8.8 years; median, 7 years). Twelve percent (n = 58) had choroid plexus calcifications, (age range, 0.1-8.8 years). Dural calcifications were rare, present in 1% (n = 6; age range, 2.9-8.7 years). Physiologic intracranial calcifications may be found in the first decade, principally in children older than 5 years. Most epithalamic calcifications are habenular. Pineal and habenular calcifications were never present in children younger than 3 and 2 years, respectively. Choroid plexus calcifications may be present in the very young. Dural calcifications are rare.


Estimating fatty alcohol contributions to the environment from laundry and personal care products using a market forensics approach.
Fatty alcohol-based surfactants are widely used in detergents and personal care products; they are typically disposed of down-the-drain and are degraded or removed during wastewater treatment. Analytical data had shown concentration and profile differences between regions of the United States. Market sales data were purchased relevant to the sampling dates. In combination with analysis of the fatty alcohol profiles in the top selling products, the influent profiles were reconstructed and compared to the whole U.S. sales data. The per capita usage rate for fatty alcohols through these 4000+ top selling products was 4.9 g per day, with 88% arising from liquid laundry detergents and hand dish detergents. This extrapolates to a national usage of 185,000 tonnes per year. There were significant differences in the purchasing habits of the inhabitants across the four regions sampled, although this had minimal impact on the fatty alcohol profile which was dominated by the C12 moiety. The U.S. market was also dominated by petrochemically-sourced chemicals. This market forensics approach using purchased sales data was able to extend our knowledge of the fate of these chemicals without a major (expensive) sampling and analytical campaign.


Implications of Internet availability of genomic information for public health practice.
Tensions in the field have emerged over how best to communicate to the public about genomic discoveries in an era of direct-to-consumer (DTC) DNA testing services available through the Internet. Concerns over what the psychological and behavioral response might be to a nuanced, multiplex risk message have spurred some to offer caution in communicating to the public about personalized risk until the necessary research has been completed on how to communicate effectively. The popularization of DTC testing services, along with a spreading Internet culture on transparency for personal data, may make 'waiting to communicate' a moot point. To steer communication efforts in the midst of increasing access to personal genomic information, a self-regulation framework is presented. The framework emphasizes the importance of presenting a coherent message in all communiqués about public health genomics. Coherence should be based on an evidence-based model of how the public processes information about health conditions and an emphasis on risk-to-action links. Recommendations from the President's Council of Advisors for Science and Technology are reviewed as a way of identifying targets of opportunity for structured communications both within the healthcare system and in the broader external ecosystem of publicly available health information technologies.


Analogs of cyclic AMP decrease gamma-aminobutyric acidA receptor-mediated chloride current in cultured rat hippocampal neurons via an extracellular site.
We have studied the effects of the membrane-permeant cyclic AMP analogs 8-bromo-cyclic AMP and 8-(4-chlorophenylthio)-cyclic AMP (CPT-cAMP) on the gamma-aminobutyric acidA (GABAA) receptor-mediated chloride current in cultured rat hippocampal neurons. External perfusion with 8-bromo-cyclic AMP or CPT-cAMP caused a reversible, concentration-dependent decrease in the response to GABA. Adding the protein kinase inhibitor H-8 to the perfusing medium or the intracellular recording solution did not affect the response to GABA, which was decreased by CPT-cAMP as before. L858051, a water-soluble derivative of the adenylate cyclase activator forskolin, did not decrease the response to GABA even in the presence of the phosphodiesterase inhibitor 3-isobutylmethylxanthine. External cyclic AMP also caused a reversible, concentration-dependent decrease in the response to GABA with a potency similar to that of 8-Br-cAMP. When cAMP was present in the intracellular recording solution cAMP and CPT-cAMP decreased the response to GABA as before. These experiments suggest that analogs of cAMP decrease GABAA receptor-activated chloride current by acting at an extracellular site.


Lipoprotein access to MHC class I presentation during infection of murine macrophages with live mycobacteria.
Following uptake by macrophages, live mycobacteria initially reside within an immature phagosome that resists acidification and retains access to recycling endosomes. Glycolipids are exported from the mycobacterial phagosome and become available for immune recognition by CD1-restricted T cells. The aim of this study was to explore the possibility that lipoproteins might similarly escape from the phagosome and act as immune targets in cells infected with live mycobacteria. We have focused on a 19-kDa lipoprotein from Mycobacterium tuberculosis that was previously shown to be recognized by CD8(+) T cells. The 19-kDa Ag was found to traffic separately from live mycobacteria within infected macrophages by a pathway that was dependent on acylation of the protein. When expressed as a recombinant protein in rapid-growing mycobacteria, the 19-kDa Ag was able to deliver peptides for recognition by MHC class I-restricted T cells by a TAP-independent mechanism. Entry into the class I pathway was rapid, dependent on acylation, and could be blocked by killing the mycobacteria by heating before infection. Although the pattern of 19-kDa trafficking was similar with different mycobacterial species, preliminary experiments suggest that class I presentation is more efficient during infection with rapid-growing mycobacteria than with the slow-growing bacillus Calmette-Guérin vaccine strain.


SERRS. In situ substrate formation and improved detection using microfluidics.
Surface-enhanced resonance Raman scattering (SERRS) of a model derivative of TNT was detected using a microflow cell designed within the framework of the lab-on-a-chip concept, using only the analyte and readily available reagents. The SERRS substrate, silver colloid, was prepared in situ, on-chip, by borohydride reduction of silver nitrate. The silver colloid was imaged within the chip using a white light microscope in either transmission or, due to the high reflectivity of the colloid, reflection mode. A fine stream of colloid approximately 30 microm in width was formed in a 250-microm-wide channel at the point where the colloid preparation reagents met. The chip was designed to produce a concentrated stream of colloid within a laminar regime, such that particles did not readily disperse into the fluid. One result of this was to reduce the effective volume of analysis. Attempts to deliberately disrupt this stream with microstructured pillars, fabricated in the fluidic channels, were unsuccessful. The chip was also designed to have the appropriate dimensions for detection using a modern Raman microscope system, which collects scattering from a very small volume. A dye derived from TNT was used as a model analyte. Quantitative behavior was obtained over 4 orders of magnitude with a detection limit of 10 fmol. This performance is between 1 and 2 orders of magnitude better than that achieved using a macroflow SERRS cell. The technique has the added advantage that both reagent consumption and effluent production are greatly reduced, leading to reduced operating costs and a decreased environmental impact


A nationally consistent framework for identifying interstate waters with applications for the national listing of fish advisories.
A 1988 survey, funded by the US Environmental Protection Agency (EPA) and conducted by the American Fisheries Society, identified the need to standardize the approaches for evaluating risks and developing fish consumption advisories that are comparable across different jurisdictions. A major tool for evaluating the progress in developing such nationally consistent information is EPA's web-based National Listing of Fish Advisories (NLFA) database, which has archived fish advisory information since 1993. The NLFA comprises both a database and Geographic Information System mapping components that are implemented using the National Hydrography Dataset (NHD). EPA and the US Geological Survey have developed an enhanced NHD product (NHDPlus) that is applied to define an interstate waters framework for the conterminous USA. This NHDPlus-based framework provides an efficient watershed-oriented approach for identifying interstate advisories from NLFA. We provide summaries of (1) the degree of consistency documented for inland waters where states have issued advisories for shared interstate NHD reaches and (2) the patterns for interstate advisories organized according to the ecoregions developed for EPA's Wadeable Streams Assessment. Approaches are also discussed for addressing interstate consistency issues for fish advisories in coastal waters making use of the NHDPlus combined with other nationally consistent frameworks, such as the 12-digit hydrologic unit code subwatersheds in the Watershed Boundary Dataset. Probability survey methods are recommended as a way to promote increased interjurisdictional consistency in the development of the monitoring and risk assessment conclusions reflected in NLFA, as well as in other EPA water quality-based programs.


The ClpX chaperone modulates assembly of the tubulin-like protein FtsZ.
Summary Assembly of the tubulin-like cytoskeletal protein FtsZ into a ring structure establishes the location of the nascent division site in prokaryotes. Factors that modulate FtsZ assembly are essential for ensuring the precise spatial and temporal regulation of cytokinesis. We have identified ClpX, the substrate recognition subunit of the ClpXP protease, as an inhibitor of FtsZ assembly in Bacillus subtilis. Genetic data indicate that ClpX but not ClpP inhibits FtsZ-ring formation in vivo. In vitro, ClpX inhibits FtsZ assembly in a ClpP-independent manner through a mechanism that does not require ATP hydrolysis. Together our data support a model in which ClpX helps maintain the cytoplasmic pool of unassembled FtsZ that is required for the dynamic nature of the cytokinetic ring. ClpX is conserved throughout bacteria and has been shown to interact directly with FtsZ in Escherichia coli. Thus, we speculate that ClpX functions as a general regulator of FtsZ assembly and cell division in a wide variety of bacteria.


Proposal and analysis of two-cavity Fabry-Perot structures based on fiber Bragg gratings.
An all-fiber two-cavity Fabry-Perot (FP) configuration based on fiber Bragg gratings (FBGs) is proposed. The characteristics of transmission spectra for the two-cavity FP structure are theoretically analyzed and comprehensively modeled. The explicit expression of the transmission coefficient for the structures is derived. The general conditions for the lengths of two cavities and reflectivities of FBGs are presented to produce the single resonant transmission peak at the central wavelength in the FBG stop band. Based on the theoretical analysis, the transmission spectra of symmetric and asymmetric two-cavity FP structures are simulated, and the simulation results are discussed and explained qualitatively. The design guidelines of the device, including the choices of cavity lengths, grating lengths, and index modulation depths, are concluded. The results show that when the increasing of the cavity length of a single-cavity FP structure results in multiple resonant peaks in the stop band, the two-cavity FP structures of the same length can inhibit the secondary resonant peaks and keep the main peak without degrading the performance through appropriately designing the cavity lengths and FBGs. Finally, the fabrication error tolerances of the structures, including inaccurate cavity lengths and reflectivities of FBGs, are calculated and discussed.


Psychiatric disorders in mildly and severely mentally retarded urban children and adolescents: epidemiological aspects.
A total of 149 children aged 13-17 years were examined. 83 were mildly and 66 severely mentally retarded. These children, especially the severely retarded ones, are representative of all mentally retarded children born in 1966-1970 and living in Göteborg, Sweden. 64% of the severely mentally retarded and 57% of the mildly mentally retarded children were suffering from a handicapping psychiatric condition. Autism-like 'psychotic behaviour' was common in the severely retarded. 0.2% of the total child population aged 13-17 years suffering from the combination of mental retardation and 'psychotic behaviour'. Epilepsy was associated with psychiatric abnormality, but Down's syndrome was generally not so associated.


Effects of suicide bereavement on mental health and suicide risk.
Between 48 million and 500 million people are thought to experience suicide bereavement every year. Over the past decade, increased policy attention has been directed towards suicide bereavement, but with little evidence to describe the effect of exposure or to provide appropriate responses. We used a systematic approach to carry out a narrative review of studies of the effect of suicide bereavement on mortality, mental health, and social functioning, and compared them with effects from other bereavements. We found 57 studies that satisfied strict inclusion criteria. Results from these studies suggested that exposure to suicide of a close contact is associated with several negative health and social outcomes, depending on an individual's relationship to the deceased. These effects included an increased risk of suicide in partners bereaved by suicide, increased risk of required admission to psychiatric care for parents bereaved by the suicide of an offspring, increased risk of suicide in mothers bereaved by an adult child's suicide, and increased risk of depression in offspring bereaved by the suicide of a parent. Some evidence was shown for increased rejection and shame in people bereaved by suicide across a range of kinship groups when data were compared with reports of relatives bereaved by other violent deaths. Policy recommendations for support services after suicide bereavement heavily rely on the voluntary sector with little input from psychiatric services to address described risks. Policymakers should consider how to strengthen health and social care resources for people who have been bereaved by suicide to prevent avoidable mortality and distress.


Hypocellularity in myelodysplastic syndrome is an independent factor which predicts a favorable outcome.
Hypocellular myelodysplastic syndrome (MDS) represents only a small portion of MDS, of which, the clinical significance has not been well-defined. By using currently accepted age-adjusted criteria to define hypocellularity as <30% in patients <70 years old, and <20% in >70 years old, we identified 163 (15.5%) hypocelluar MDS from 1049 consecutive adult MDS patients over an 11-year period (1995-2006). Compared to normal/hypercellular MDS, hypocellular MDS patients were younger (p<0.01), less anemic (p=0.02), but more neutropenic (p<0.001) and thrombocytopenic (p=0.05), and had a comparable cytogenetic risk group distribution (p=0.09) and international prognostic scores (IPSS, p=0.13). With a median follow-up of 52 months, hypocellular MDS showed a favorable overall survival (56 months versus 28 months, log-rank p<0.0001) over normal/hypocellular MDS, and this survival preference was also demonstrated in all IPSS groups and cytogenetic risk groups, and was independent of all other risk factors (Cox regression test, p=0.01). In conclusion, our study demonstrated that hypocellular MDS has characteristic clinicopathologic features, and bone marrow hypocellularity in MDS is an independent factor which predicts a favorable outcome.


Carvedilol modifies antioxidant status of patients with stable angina.
The aim of this study was to evaluate the effect of carvedilol on the enzymatic antioxidative defence and plasma antioxidative activity in patients with stable angina. The study comprised 30 patients, aged 37-49 years with stable angina. Patients received carvedilol in escalating doses of 12.5 mg/24 h, 25 mg/24 h, and 50 mg/24 h for 4 weeks each. The control group was matched for age and gender, and consisted of 12 healthy volunteers, aged 39-49 years. Blood samples were collected from the cubital vein before and 4, 8 and 12 weeks after the therapy from the patients and once from the control group. For all the subjects, the superoxide dismutase (SOD-1), glutathione peroxidase (GSH-Px), catalase (CAT) activities in the erythrocytes and the antioxidant activity of the blood plasma were determined. The enzymatic antioxidative defence was significantly decreased in patients with stable angina in comparison to the healthy subjects. During the carvedilol therapy, an increase in the SOD-1, GSH-Px and CAT activities was observed. Moreover, 8 and 12 weeks after carvedilol therapy, the GSH-Px activity did not differ significantly from that observed in the group of healthy subjects. Carvedilol also increased the plasma antioxidative activity in patients with stable angina, but its level remained significantly lower than in the control group. In conclusion, carvedilol enhances antioxidant defense mechanisms in patients with chronic stable angina pectoris.


Genetic structure of mountain lion (Puma concolor) populations in California.
Analysis of 12 microsatellite loci from431 mountain lions (Puma concolor)revealed distinct genetic subdivision that wasassociated with geographic barriers andisolation by distance in California. Levels ofgenetic variation differed among geographicregions, and mountain lions that inhabitedcoastal areas exhibited less heterozygositythan those sampled inland. The San FranciscoBay and Sacramento-San Joaquin River Delta, theCentral Valley, and the Los Angeles Basinappeared to be substantial barriers to geneflow, and allele frequencies of populationsseparated by those features differedsubstantially. A partial barrier to gene flowappeared to exist along the crest of the SierraNevada. Estimated gene flow was high amongmountain lions inhabiting the Modoc Plateau,the western Sierra Nevada, and northern sectionof the eastern Sierra Nevada. SouthernCalifornia mountain lion populations mayfunction as a metapopulation; however, humandevelopments threaten to eliminate habitat andmovement corridors. While north-south geneflow along the western Sierra Nevada wasestimated to be very high, projected loss andfragmentation of foothill habitat may reducegene flow and subdivide populations. Preservation of existing movement corridorsamong regions could prevent population declinesand loss of genetic variation. This studyshows that mountain lion management andconservation efforts should be individualizedaccording to region and incorporatelandscape-level considerations to protecthabitat connectivity.


Examining the relationship between use of sexually explicit media and sexual risk behavior in a sample of men who have sex with men in Norway.
The purpose of this study was to investigate consumption patterns of gay-oriented sexually explicit media (SEM) among men who have sex with men (MSM) in Norway, with a particular emphasis on a possible relationship between gay SEM consumption and HIV risk behavior. Participants included 529 MSM living in Norway recruited online to complete a SEM consumption and sexual risk survey. Of the 507 participants who responded to the all items measuring exposure to SEM, 19% reported unprotected anal intercourse with a casual partner (UAI) in last 90 days, and 14% reported having had sero-discordant UAI. Among those with UAI experience, 23% reported receptive anal intercourse (R-UAI) and 37% reported insertive anal intercourse (I-UAI). SEM consumption was found to be significantly associated with sexual risk behaviors. Participants with increased consumption of bareback SEM reported higher odds of UAI and I-UAI after adjusting for other factors using multivariable statistics. MSM who started using SEM at a later age reported lower odds of UAI and I-UAI than MSM who started earlier. Future research should aim at understanding how MSM develop and maintain SEM preferences and the relationship between developmental and maintenance factors and HIV sexual risk behavior.