What Young People Need to Make Better-Informed Decisions When Communicating With Digital Images: Implications for Mental Health and Well-Being.
Sixty-eight young people contributed to a Design Thinking Challenge created to elicit a better understanding of their electronic image-sharing experiences, the helpful and harmful consequences of image-sharing to adolescent mental health and safety, and promising interventions that allow young people to make more positive decisions and minimize their risks when sharing images through electronic devices. Through this collaborative group-based process, each co-design group engaged in a four-phase process to discover, define, develop, and deliver an intervention that took the form of a paper-based mobile app prototype. Young people reported that they need information and advice to support their and others' online decision making, help making situational decision-making skills for managing online interactions, and means to control information and images that can be accessed and distributed. Detailed app features that they required to address their decision-making needs are also discussed. These app intervention features highlight what young people need to make better-informed decisions when communicating through images electronically.


Cross-Fostering Implications for Pig Mortality, Welfare and Performance.
This study aimed to (1) identify cross-fostering (CF) practices employed on a commercial farm; (2) characterize CF pigs according to litter of origin traits, and (3) investigate the implications of CF practices on pig mortality, performance and welfare. This was an observational study whereby pigs were managed according to normal farming practice. Pigs (n = 1,016) born within 1 week were classified as non-CF (NCF); CF during the first (CFW1) and second or third (CFW2+) weeks of lactation. Pigs were individually weighed and inspected for the presence of tail (TL), ear (EL) and body lesions (BL) at weaning (7.03 ± 1.61 kg) and at the end of the first (12.9 ± 3.03 kg) and second (31.9 ± 5.50 kg) weaner and grower (66.3 ± 9.12 kg) stages. Mortality was recorded through to slaughter (c. 115 kg). At slaughter, TL were scored and carcass characteristics, presence of pleurisy, enzootic pneumonia, pericarditis and heart condemnations were recorded. 40.8% of CF pigs were CFW1; ANOVA tests revealed these were born to sows with a higher number of piglets born alive than NCF pigs (14.6 ± 2.61 and 12.8 ± 2.68, respectively). The remaining 59.2% of CF pigs were CFW2+; these were, on average, 0.14 kg lighter at birth than NCF pigs. Therefore, a nested case control design was retrospectively applied whereby pigs with complete records to slaughter, were matched for these variables to investigate associations between CF weeks, welfare and performance traits. Growth performance did not differ between CF week (P > 0.05); however, CFW2+ carcasses were 4.9 kg lighter (P < 0.05) compared with NCF and CFW1 pigs. EL were more likely in CFW1 compared to NCF and CFW2+ (P < 0.05) pigs. To investigate the effect of CF week on the risk of mortality, all 1,016 pigs were used. CF pigs were at higher risk of death (P < 0.05) with similar odds in CFW1 and CFW2+ pigs compared with NCF pigs, although other underlying factors could contribute to this result. Performance and health traits were similar between CF weeks. Early cross-fostering appeared to influence the presence of ear lesions but the mechanism is likely indirect and difficult to explain.


Venture funding for science-based African health innovation.
While venture funding has been applied to biotechnology and health in high-income countries, it is still nascent in these fields in developing countries, and particularly in Africa. Yet the need for implementing innovative solutions to health challenges is greatest in Africa, with its enormous burden of communicable disease. Issues such as risk, investment opportunities, return on investment requirements, and quantifying health impact are critical in assessing venture capital's potential for supporting health innovation. This paper uses lessons learned from five venture capital firms from Kenya, South Africa, China, India, and the US to suggest design principles for African health venture funds. The case study method was used to explore relevant funds, and lessons for the African context. The health venture funds in this study included publicly-owned organizations, corporations, social enterprises, and subsidiaries of foreign venture firms. The size and type of investments varied widely. The primary investor in four funds was the International Finance Corporation. Three of the funds aimed primarily for financial returns, one aimed primarily for social and health returns, and one had mixed aims. Lessons learned include the importance of measuring and supporting both social and financial returns; the need to engage both upstream capital such as government risk-funding and downstream capital from the private sector; and the existence of many challenges including difficulty of raising capital, low human resource capacity, regulatory barriers, and risky business environments. Based on these lessons, design principles for appropriate venture funding are suggested. Based on the cases studied and relevant experiences elsewhere, there is a case for venture funding as one support mechanism for science-based African health innovation, with opportunities for risk-tolerant investors to make financial as well as social returns. Such funds should be structured to overcome the challenges identified, be sustainable in the long run, attract for-profit private sector funds, and have measurable and significant health impact. If this is done, the proposed venture approach may have complementary benefits to existing initiatives and encourage local scientific and economic development while tapping new sources of funding.


The role of peptides cleaved from protein precursors in eliciting plant stress reactions.
As sessile organisms, plants are exposed to diverse abiotic and biotic stresses, and thus have developed complex signaling mechanisms that orchestrate multiple stress responses. Plant peptides have recently emerged as key signaling molecules of stress responses, not only to mechanical wounding and pathogen infection but also to nutrient imbalance, drought and high salinity. The currently identified stress-related signaling peptides in plants are derived from proteolytic processing of protein precursors. Here, we review these protein-derived peptides and the evidence for their functions in stress signaling. We recommend potential research directions that could clarify their roles in stress biology, and propose possible crosstalk with regard to the physiological outcome. The stress-centric perspective allows us to highlight the crucial roles of peptides in regulating the dynamics of stress physiology. Inspired by historic and recent findings, we review how peptides initiate complex molecular interactions to coordinate biotic and abiotic stress responses in plants.


Estimation of feeding value of four tropical forage species at two stages of maturity.
The feeding value of four tropical grasses was assessed through voluntary intake and digestibility studies using yearling Brahman x British steers (average BW = 256 +/- 34 kg). The digestibility of OM was estimated using total fecal collection (TFC), in vitro OM digestibility (IVOMD), and by estimating fecal production using insoluble acid detergent fiber (IADF) as an indigestible marker. The four grasses consisted of bahiagrass (Paspalum notatum), limpograss (Hemarthria altissima), bermudagrass (Cynodon dactylon), and stargrass (Cynodon spp.). Grass was harvested at two stages of maturity (approximately 4 and 10 wk). Forages were ground (5 to 10 cm) and offered to steers ad libitum. Forage treatments were assigned randomly to steers over eight 28-d periods and repeated over two consecutive years. Total forage offered and refused was determined during a 14-d sample collection period. For determination of fecal output, steers were placed into metabolism crates for 7 d. Composited samples of forage offered, forage refused, and feces of each steer at each period were analyzed for DM, OM, NDF, ADF, IADF, IVOMD, and CP. All digestibility results were calculated on an OM basis. There were year x grass x maturity interactions (P < 0.01) for all measures of forage quality, except CP. Increased maturity resulted in a 37.8% decrease (P < 0.001) in CP concentration when averaged across all forages. Four-week bermudagrass contained the greatest (P < 0.05) concentration of CP compared with all other grasses at both maturities, except 4-wk stargrass. Bahiagrass IVOMD did not differ among 4- and 10-wk maturities in both years; however, the IVOMD content of both stargrass and bermudagrass decreased (P < 0.05) when these forages matured from 4 to 10 wk. Apparent OM digestibility, determined by TFC, was greater (P < 0.05) than OM digestibility determined by IVOMD and IADF for all forages except bahiagrass, for which IADF did not differ from TFC. In Year 1, OM intake (OMI) of 10-wk limpograss was less (P < 0.05) than all other 4-wk forages. In Year 2, voluntary OMI of 10-wk limpograss was less (P < 0.05) than all grass x maturity combinations, except for 10-wk bermudagrass. These data suggest that important differences exist in changes in nutrient quality associated with increased maturity in tropical forages. Among the forages assessed in this study, bahiagrass seems to better retain nutrient quality when maturing from 4 to 10 wk.


Evaluation, using extracted human teeth, of Ricetral as a storage medium for avulsions--an in vitro study.
The prognosis of teeth replanted following avulsion is determined by the extra-alveolar time and storage medium used. This study was undertaken to determine the efficacy of an oral rehydration solution 'Ricetral', in retaining the vitality of periodontal ligament cells when used as a storage medium for avulsed teeth prior to replantation. The study consisted of a comparative evaluation between Ricetral and two currently recommended solutions, Hank's balanced salt solution (HBSS) and milk. Thirty extracted teeth were dried for 30min and soaked in the respective storage media for 45min. The periodontal ligament cells were isolated by an enzyme treatment with collagenase and trypsin. The cells were evaluated for vitality by trypan blue staining and number of vital cells counted in a hemocytometer. Statistical analysis revealed that cell vitality was high with Ricetral and HBSS, but poor with milk.


Bone health in cancer patients: ESMO Clinical Practice Guidelines.
There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling. This endocrine disturbance results in accelerated bone loss and an increased risk of osteoporosis and fractures that can have a significant negative impact on the lives of the rapidly expanding number of long-term cancer survivors. Finally, the bone marrow micro-environment is also intimately involved in the metastatic processes required for cancer dissemination, and there are emerging data showing that, at least in some clinical situations, the use of bone-targeted treatments can reduce metastasis to bone and has potential impact on patient survival.


Behavioral factors and the risk of viral infection: essential aspects during the COVID‑19 pandemic.
The current COVID-19 pandemic continues for over eleven months. Several nutritional and behavioural aspects have been associated with an increased inflammatory state, or oxidative stress, which could negatively affect the course of COVID-19. As research has shown, metabolic diseases, including obesity, or type 2 diabetes mellitus (T2DM), in which proper diet is especially important, increase the risk of the COVID-19 infection and can exacerbate its course. This should be taken into account particularly in the areas with high prevalence of obesity and T2DM, such as the Western countries. In our paper, we have briefly summarised the harmful and beneficial nutritional and behavioural aspects, essential during the COVID-19 pandemic, which are present in particular among patients suffering from obesity and T2DM.


Tyrosine phosphorylation of calponins. Inhibition of the interaction with F-actin.
The phosphorylation-dephosphorylation of serine and threonine residues of calponin is known to modulate in vitro its interaction with F-actin and is thought to regulate several biological processes in cells, involving either of the calponin isoforms. Here, we identify, for the first time, tyrosine-phosphorylated calponin h3 within COS 7 cells, before and after their transfection with the pSV vector containing cDNA encoding the cytoplasmic, Src-related, tyrosine kinase, Fyn. We then describe the specific tyrosine phosphorylation in vitro of calponin h1 and calponin h3 by this kinase. 32P-labeling of tyrosine residues was monitored by combined autoradiography, immunoblotting with a specific phosphotyrosine monoclonal antibody and dephosphorylation with the phosphotyrosine-specific protein phosphatase, YOP. PhosphorImager analyses showed the incorporation of maximally 1.4 and 2.0 mol of 32P per mol of calponin h3 and calponin h1, respectively. As a result, 75% and 68%, respectively, of binding to F-actin was lost by the phosphorylated calponins. Furthermore, F-actin, added at a two- or 10-fold molar excess, did not protect, but rather increased, the extent of 32P-labeling in both calponins. Structural analysis of the tryptic phosphopeptides from each 32P-labeled calponin revealed a single, major 32P-peptide in calponin h3, with Tyr261 as the phosphorylation site. Tyr261 was also phosphorylated in calponin h1, together with Tyr182. Collectively, the data point to the potential involvement, at least in living nonmuscle cells, of tyrosine protein kinases and the conserved Tyr261, located in the third repeat motif of the calponin molecule, in a new level of regulation of the actin-calponin interaction.


Effect of feeding single-dam or pooled colostrum on maternally derived immunity in dairy calves.
The role of colostrum management in providing adequate immunological protection to neonatal calves has been widely investigated, and thresholds for colostrum quality, as well as optimum volume and timing for colostrum feeding have been established. However, limited information is available on the effect of colostrum source (single dam or pooled) on passive immunity, as well as subsequent antibody survival in the calf. This study aimed to assess the effect of feeding single-dam colostrum (own and other dam) or pooled colostrum on transfer of passive immunity, and also investigate the rate of depletion of disease-specific antibodies among dairy calves. In total, 320 cows and 119 dairy heifer calves were enrolled in the study. Calves were blood-sampled immediately after birth and received either own-dam, other-dam, or pooled colostrum. Calves were blood-sampled at 24 h to assess serum IgG concentrations and at monthly intervals thereafter to document disease-specific antibody survival. Mean colostrum IgG concentration was higher for other-dam treatment group, whereas own-dam and pooled treatments were similar. For all treatment groups, the mean IgG concentration was >80 mg/mL, exceeding the quality threshold of 50 mg/mL. Mean calf serum IgG concentration was lower for calves fed pooled colostrum compared with those that received colostrum from a single cow. There was a negative association with 24-h serum IgG and calf birth bodyweight; calves <30 kg at birth had the highest 24-h serum IgG concentration. Survival of antibodies to bovine viral diarrhea, Salmonella infection, leptospirosis, bovine parainfluenza 3 virus, bovine respiratory syncytical virus, rotavirus, and coronavirus was not associated with colostrum source; however, antibodies to infectious bovine rhinotracheitis had a greater period of survival among calves fed own-dam colostrum. We found that feeding single-dam colostrum can thus improve calf immunity through increased serum IgG levels and antibody survival rates. Furthermore, we hypothesize that immune exclusion may occur with pooled colostrum; therefore, providing pooled colostrum may still be a good practice as long as it can be ensured that enough antibodies are absorbed into the blood stream to deal with pathogens calves may encounter because different dams may have antibodies against different strains of viruses and bacteria, yielding cross protection.


Promoting COVID-19 vaccine acceptance: recommendations from the Lancet Commission on Vaccine Refusal, Acceptance, and Demand in the USA.
Since the first case of COVID-19 was identified in the USA in January, 2020, over 46 million people in the country have tested positive for SARS-CoV-2 infection. Several COVID-19 vaccines have received emergency use authorisations from the US Food and Drug Administration, with the Pfizer-BioNTech vaccine receiving full approval on Aug 23, 2021. When paired with masking, physical distancing, and ventilation, COVID-19 vaccines are the best intervention to sustainably control the pandemic. However, surveys have consistently found that a sizeable minority of US residents do not plan to get a COVID-19 vaccine. The most severe consequence of an inadequate uptake of COVID-19 vaccines has been sustained community transmission (including of the delta [B.1.617.2] variant, a surge of which began in July, 2021). Exacerbating the direct impact of the virus, a low uptake of COVID-19 vaccines will prolong the social and economic repercussions of the pandemic on families and communities, especially low-income and minority ethnic groups, into 2022, or even longer. The scale and challenges of the COVID-19 vaccination campaign are unprecedented. Therefore, through a series of recommendations, we present a coordinated, evidence-based education, communication, and behavioural intervention strategy that is likely to improve the success of COVID-19 vaccine programmes across the USA.


The effects of deep diaphragmatic breathing and focused attention on dental anxiety in a private practice setting.
High dental anxiety is pervasive and associated with treatment avoidance and poor oral health. Ideally, anxiety reduction techniques should be easy to use, low in cost, non-pharmacological, comfortable, and effective. This study compared the effectiveness of two self-taught anxiety reduction techniques--breathing and focused attention--with a control group. Anxiety was assessed in 272 adult private dental practice patients with a modified dental anxiety scale-revised. Frequency of oral health care visits in the last 10 years to all dentists, including the current dentist, was collected. Immediately prior to the dental procedure, participants in the two experimental groups were given written instructions outlining the respective anxiety reduction technique they were to use. Efficacy of technique was assessed by subjective comparison to anxiety during previous oral health treatment. Participants also listed techniques that they believed to be effective for anxiety reduction. Twenty-six participants (9.56%) scored high in dental anxiety. High anxiety was associated with infrequent oral health care visits. Compared to the recall of anxiety experienced during prior treatment, there were no significant differences in anxiety between breathing, focusing, and control groups. But there was a trend toward decreased anxiety overall. Controls who reported infrequent visits and use of their own anxiety reduction technique showed significantly reduced anxiety. Dental patients employ numerous strategies for anxiety reduction. Anxiety reduction techniques not yet practiced may place unwanted expectations on patients. It is suggested that oral health care practitioners be aware of the patient's preferred technique for coping with anxiety and encourage them to use self-help techniques.


Adaptive multiscale complexity analysis of fetal heart rate.
Per partum fetal asphyxia is a major cause of neonatal morbidity and mortality. Fetal heart rate monitoring plays an important role in early detection of acidosis, an indicator for asphyxia. This problem is addressed in this paper by introducing a novel complexity analysis of fetal heart rate data, based on producing a collection of piecewise linear approximations of varying dimensions from which a measure of complexity is extracted. This procedure specifically accounts for the highly non-stationary context of labor by being adaptive and multiscale. Using a reference dataset, made of real per partum fetal heart rate data, collected in situ and carefully constituted by obstetricians, the behavior of the proposed approach is analyzed and illustrated. Its performance is evaluated in terms of the rate of correct acidosis detection versus the rate of false detection, as well as how early the detection is made. Computational cost is also discussed. The results are shown to be extremely promising and further potential uses of the tool are discussed. MATLAB routines implementing the procedure will be made available at the time of publication.


The differing adipocyte morphologies of deep versus superficial midfacial fat compartments: a cadaveric study.
Anatomical studies show that facial fat is partitioned into distinct compartments, with the nasolabial fat pad in a superficial compartment and the deep medial cheek fat in a deep compartment. Gross morphologic differences may exist between these fat depots, but this has never been established at the cellular level. Adipose tissue specimens from nasolabial fat and deep medial cheek fat pads were obtained from 63 cadaveric specimens (38 female and 25 male cadavers) aged 47 to 101 years (mean, 71 years). Thirty-seven cadavers had a normal body mass index (≤25 kg/m) and 26 cadavers had a high body mass index (>25 kg/m). Cross-sectional areas of individual adipocytes were calculated digitally and averaged from histologic sections of the adipose tissue samples. The average adipocyte size of nasolabial fat is significantly (p < 0.0001) larger than that of deep medial cheek fat. The average adipocyte size in both nasolabial and deep medial cheek fat is significantly (p < 0.0001) larger in subjects with high compared with low body mass index. Although the overall average adipocyte size is significantly (p < 0.0001) larger in female than in male subjects, this sexual dimorphism is lost in the nasolabial fat depots of overweight subjects and in the deep medial cheek depots of normal-weight subjects. The significantly smaller adipocyte size in deep medial cheek fat relative to nasolabial fat in elderly subjects supports the theory that deep and superficial facial fat pads are morphologically different. Future investigation of the metabolic and structural properties of these fat compartments will help us understand the different patterns of volumetric facial aging.


Health economic assessment of a scenario to promote bicycling as active transport in Stockholm, Sweden.
To conduct a health economic evaluation of a proposed investment in urban bicycle infrastructure in Stockholm County, Sweden. A cost-effectiveness analysis is undertaken from a healthcare perspective. Investment costs over a 50-year life cycle are offset by averted healthcare costs and compared with estimated long-term impacts on morbidity, quantified in disability-adjusted life years (DALYs). The results are re-calculated under different assumptions to model the effects of uncertainty. The Municipality of Stockholm (population 2.27 million) committed funds for bicycle path infrastructure with the aim of achieving a 15% increase in the number of bicycle commuters by 2030. This work is based on a previously constructed scenario, in which individual registry data on home and work address and a transport model allocation to different modes of transport identified 111 487 individuals with the physical capacity to bicycle to work within 30 min but that currently drive a car to work. Morbidity impacts and healthcare costs attributed to increased physical activity, change in air pollution exposure and accident risk are quantified under the scenario. The largest reduction in healthcare costs is attributed to increased physical activity and the second largest to reduced air pollution exposure among the population of Greater Stockholm. The expected net benefit from the investment is 8.7% of the 2017 Stockholm County healthcare budget, and 3.7% after discounting. The economic evaluation estimates that the intervention is cost-effective and each DALY averted gives a surplus of €9933. The results remained robust under varied assumptions pertaining to reduced numbers of additional bicycle commuters. Investing in urban infrastructure to increase bicycling as active transport is cost-effective from a healthcare sector perspective.


Evaluation and assessment of new disposable strip for determination of plasma potassium concentration.
Overall laboratory reproducibility for the Ames Seralyzer and plasma potassium test strips was less than 4% within the plasma reference range; and linearity extended from 2.1 to 10.2 mmol/l. Neither bilirubin nor lipaemia interfered in the analysis and selectivity for potassium over sodium was 450:1. Laboratory comparison with automated flame photometry and an indirect ion selective electrode showed a Seralyzer bias of +0.10 (+/- 25D 0.26) and +0.11 (0.27) mmol/l. Against flame photometry, comparison of analyses by six doctors from a coronary care unit and four nurses from a renal dialysis unit showed smaller positive biases (0.06 and 0.02 mmol/l) but substantially larger error ranges (0.43 and 0.55 mmol/l, respectively). Some 49% of the nurses' and 37% of the doctors' results differed from laboratory values by more than 0.2 mmol/l. Potassium test strip results proved acceptably comparable and reproducible when produced by an experienced analyst, but greater variability in clinical hands rendered the system unsuitable for precise monitoring of potassium concentration.


Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity.
A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12-20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.


Effects of ultralow topical estriol dose on vaginal health and quality of life in postmenopausal women who underwent surgical treatment for pelvic organ prolapse.
To evaluate the efficacy of low concentrations of vaginal estriol gel in postmenopausal women with pelvic static disorders before and after vaginal surgical treatment, assessing vaginal health, sexual function, and quality of life (QoL). Women affected by genital prolapse were enrolled. Vaginal health, QoL, and sexual function were investigated at baseline (T0), before surgery (T1), and 13 weeks after surgery (T2). At baseline, participants were randomized 1:1. Women in group A (38 women) were treated daily with vaginal gel containing 50 μg estriol for 12 weeks and women in group B (37 women) did not receive any estrogen treatment. After this period and before surgery, a first examination was carried out (T1). One week after surgical treatment, group A underwent randomization 1:1 to group A1 repeating estriol vaginal gel for 12 weeks, and group A2 discontinuing the estrogen treatment. The second follow-up examination (T2) was performed at the 13th week after surgery. All aspects of vaginal health improved in group A on estriol before surgery with respect to baseline (P < 0.001). After surgery, 17 participants of group A1, 16 of group A2, and 30 of group B completed the study. Group A1 (on estriol plus surgery) further improved with respect to the presurgery estriol treatment (P < 0.01). Moreover, group A2 (T2) experienced a worsening of vaginal health versus intragroup presurgery estriol treatment (P < 0.01), and versus intergroup surgical estriol treatment (P < 0.05). QoL improved in women only after surgery, with (P < 0.01) or without (P < 0.05) estriol treatment. Finally, the sexual function of participants on estriol before surgery did not change. On the contrary, it improved after surgery in both participants on estriol (P < 0.001) and without estriol (P < 0.01). Moreover, surgical estriol participants had a better score than surgical no-estriol participants (P < 0.05). Estriol vaginal gel (0.005%) administration significantly improved the vaginal health of natural postmenopausal women before and after vaginal surgery. Both sexual health and QoL also significantly improved after surgery.


Hepatitis C virus genotypes in north eastern Algeria: A retrospective study.
To determine the frequency of various hepatitis C virus (HCV) genotypes present in patients from north eastern Algeria. This is a retrospective cross-sectional study of 435 HCV infected patients from northeast Algeria, detected in the Sadelaoud laboratory and diagnosed between January 2010 and December 2012. The patients were diagnosed with HCV infection in their local hospitals and referred to be assessed for HCV genotype before the antiviral treatment. Demographic information (sex, age and address), genotype, subtype and viral load were retrieved from the patient medical records. The serum samples were tested by the type-specific genotyping assay. The majority of the patients (82.5%) were from the central part of the examined region (P = 0.002). The mean age of the patients studied was 53.6 ± 11.5 years. HCV genotype 1 was the most frequent (88.7%), followed by genotypes 2 (8.5%), 4 (1.1%), 3 (0.9%) and 5 (0.2%). Genotype 6 was not detected in these patients. Mixed infection across the HCV subtypes was detected in twenty patients (4.6%). The genotype distribution was related to age and region. Genotype 1 was significantly less frequent in the ≥ 60 age group than in the younger age group (OR = 0.2; 95%CI: 0.1-0.5, P < 0.001). Furthermore, genotype 1 was more frequent in the central part of the examined region than elsewhere (P < 0.01). The HCV genotype (type 1b was dominant) distribution in Algeria is different from those in other northern countries of Africa.


The addition of body armor diminishes dynamic postural stability in military soldiers.
Poor postural stability has been identified as a risk factor for lower extremity musculoskeletal injury. The additional weight of body armor carried by Soldiers alters static postural stability and may predispose Soldiers to lower extremity musculoskeletal injuries. However, static postural stability tasks poorly replicate the dynamic military environment, which places considerable stress on the postural control system during tactical training and combat. Therefore, the purpose of this study was to examine the effects of body armor on dynamic postural stability during single-leg jump landings. Thirty-six 101st Airborne Division (Air Assault) Soldiers performed single-leg jump landings in the anterior direction with and without wearing body armor. The dynamic postural stability index and the individual stability indices (medial-lateral stability index, anterior-posterior stability index, and vertical stability index) were calculated for each condition. Paired sample t-tests were performed to determine differences between conditions. Significant differences existed for the medial-lateral stability index, anterior-posterior stability index, vertical stability index, and dynamic postural stability index (p < 0.05). The addition of body armor resulted in diminished dynamic postural stability, which may result in increased lower extremity injuries. Training programs should address the altered dynamic postural stability while wearing body armor in attempts to promote adaptations that will result in safer performance during dynamic tasks.


Subcortical Ischemic Vascular Cognitive Impairment: Insights from Reaction Time Measures.
In this study, reaction time (RT), intraindividual variability (IIV), and errors, and the effects of practice and processing load upon such function, were compared in patients with subcortical ischemic vascular cognitive impairment (SIVCI) [n = 27] and cognitively healthy older adults (CH) [n = 26]. Compared to CH aging, SIVCI was characterized by a profile of significantly slowed RT, raised IIV, and higher error levels, particularly in the presence of distracting stimuli, indicating that the integrity and/or accessibility of the additional functions required to support high processing load, serial search strategies, are reduced in SIVCI. Furthermore, although practice speeded RT in SIVCI, unlike CH, practice did not lead to an improvement in IIV. This indicates that improvement in RT in SIVCI can in fact mask an abnormally high degree of IIV. Because IIV appears more related to disease, function, and health than RT, its status and potential for change may represent a particularly meaningful, and relevant, disease characteristic of SIVCI. Finally, a high level of within-group variation in the above measures was another characteristic of SIVCI, with such processing heterogeneity in patients with ostensibly the same diagnosis, possibly related to individual variation in pathological load. Detailed measurement of RT, IIV, errors, and practice effects therefore reveal a degree of functional impairment in brain processing not apparent by measuring RT in isolation.


Polymeric implant materials for the reconstruction of tracheal and pharyngeal mucosal defects in head and neck surgery.
The existing therapeutical options for the tracheal and pharyngeal reconstruction by use of implant materials are described. Inspite of a multitude of options and the availability of very different materials none of these methods applied for tracheal reconstruction were successfully introduced into the clinical routine. Essential problems are insufficiencies of anastomoses, stenoses, lack of mucociliary clearance and vascularisation. The advances in Tissue Engineering (TE) offer new therapeutical options also in the field of the reconstructive surgery of the trachea. In pharyngeal reconstruction far reaching developments cannot be recognized at the moment which would allow to give a prognosis of their success in clinical application. A new polymeric implant material consisting of multiblock copolymers was applied in our own work which was regarded as a promising material for the reconstruction of the upper aerodigestive tract (ADT) due to its physicochemical characteristics. In order to test this material for applications in the ADT under extreme chemical, enzymatical, bacterial and mechanical conditions we applied it for the reconstruction of a complete defect of the gastric wall in an animal model. In none of the animals tested either gastrointestinal complications or negative systemic events occurred, however, there was a multilayered regeneration of the gastric wall implying a regular structured mucosa.In future the advanced stem cell technology will allow further progress in the reconstruction of different kind of tissues also in the field of head and neck surgery following the principles of Tissue Engineering.


Physiological response of roe deer (Capreolus capreolus) during stalking hunts depending on age.
The European roe deer (Capreolus capreolus) is a species particularly reactive to all kinds of negative stimuli. Hunting activity is one of the most potent stressors that disturbs the welfare of wild animals. During stress, various endocrine responses are elicited to improve the physical performance of the affected individual. A commonly assessed hormone for overcoming stressful situations is cortisol (CORT). In this study, plasma CORT levels in roe deer were assessed during the season of the most intense stalking hunts in Poland (summer vs. late autumn), the sex of the harvested animals (males vs. females), and age of harvest animal. In addition, the health status of the roe doe was evaluated on the basis of selected indices of blood chemistry, which could be associated with circulating cortisol levels. The mean cortisol levels were 58.066 ng/ml in the male group (summer) and 27.694 ng/ml in the female group (late autumn). Higher CORT levels were associated with a significantly lower of total cholesterol, lactate dehydrogenase, and uric acid (p < 0.05). Moreover, the mean concentration of uric acid was negatively correlated with the level of CORT in the male and female groups (p < 0.05). Together with the increase in mean CORT level, the HDL cholesterol of all the tested animals increased significantly (p < 0.05). Higher CORT in males during the summer than in females during the late autumn were most likely due to the arousal with the mating season. The level of CORT increased with the animals' age. Uric acid and age are both predictors of roe deer's serum CORT level.


Anodal transcranial direct current stimulation affects auditory cortex plasticity in normal-hearing and noise-exposed rats.
Transcranial direct current stimulation (tDCS) is a non-invasive tool capable to modulate cortical functions by affecting neuronal excitability and synaptic plasticity. Here we investigated the effects of anodal tDCS on auditory cortex (ACx) in normal-hearing rats and following a paradigm of noise-induced hearing loss (NIHL), that causes morphological alterations in ACx pyramidal neurons. Male rats exposed to intense pure tone (10 kHz) were subsequently subjected to unilateral anodal tDCS of ACx and changes in dendritic morphology and spines were assessed by Golgi-Cox staining 30 days after the onset of the acoustic trauma. Molecular and functional changes were investigated by Western immunoblotting, immunofluorescence experiments and electrophysiological recordings in brain slices. We found that NIHL altered dendritic morphology by decreasing spine density, mostly in layer 2/3 pyramidal neurons. Interestingly, tDCS increased ACx spine density, targeting apical dendrites of layer 2/3 and 5/6 pyramidal neurons in rats with normal auditory function and both apical and basal arborizations in layer 2/3 of NIHL rats. Twenty-four hours after tDCS, Bdnf and synaptophysin levels in ACx increased both in normal-hearing and noise-exposed rats. Field recordings showed that basal synaptic transmission at layer 2/3 horizontal connections was significantly reduced in noise-exposed rats compared to normal-hearing animals and, notably, input-output curves of noise-exposed animals subjected to tDCS were similar to those of normal-hearing rats. Our findings provide novel evidence that anodal tDCS affects structural plasticity in the ACx suggesting that it might be beneficial in treating cortical alterations due to cochlear damage.


The genome of Eucalyptus grandis.
Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology.


Targeting of the hair cell proteins cadherin 23, harmonin, myosin XVa, espin, and prestin in an epithelial cell model.
We have developed an advantageous epithelial cell transfection model for examining the targeting, interactions, and mutations of hair cell proteins. When expressed in LLC-PK1-CL4 epithelial cells (CL4 cells), the outer hair cell protein prestin showed faithful domain-specific targeting to the basolateral plasma membrane. We examined the consequences of mutations affecting prestin activity and assigned a targeting role to the cytoplasmic tail. The stereociliary link protein cadherin 23 (Cdh23) was targeted to the plasma membrane of CL4 cell microvilli, the topological equivalent of stereocilia. In cells coexpressing the Cdh23 cytoplasmic binding protein harmonin, a large fraction of harmonin became colocalized with Cdh23 in microvilli. Using this assay and in vitro protein binding assays, we formulated an alternative model for Cdh23-harmonin binding, in which the primary interaction is between the harmonin N-domain and a 35-residue internal peptide in the Cdh23 cytoplasmic tail. Contrary to a previous model, we found no role for the Cdh23 C-terminal PDZ (PSD-95/Dlg/ZO-1)-binding motif and observed that Cdh23 bound similar levels of harmonin with or without the exon 68 peptide. We also examined two proteins involved in stereocilium elongation. The stereociliary actin-bundling protein espin was targeted to CL4 cell microvilli and caused microvillar elongation, whereas espin with the c.2469delGTCA or c.1988delAGAG human deafness mutation showed defects in microvillar targeting and elongation. The unconventional myosin motor myosin XVa accumulated at the tips of espin-elongated microvilli, by analogy to its location in stereocilia, whereas myosin XVa with the c.4351G>A or c.4669A>G human deafness mutation did not, revealing functional deficits in motor activity.


Fermentation of isolated pectin and pectin from intact forages by pure cultures of rumen bacteria.
Studies on the rate and extent of galacturonic acid and isolated pectin digestion were carried out with nine strains of rumen bacteria (Butyrivibrio fibrisolvens H10b and D16f, Bacteroides ruminicola 23 and D31d, Lachnospira multiparus D15d, Peptostreptococcus sp. D43e, B. succinogenes A3c, Ruminococcus flavefaciens B34b, and R. albus 7). Only three strains, 23, D16f, and D31d, utilized galacturonic acid as a sole energy source, whereas all strains except A3c and H10b degraded (solubilized) and utilized purified pectin. Nutrient composition of the basal medium and separate sterilization of the substrate affected the rate and extent of fermentation for both substrates. Pectin degradation and utilization were measured with two maturity stages each of intact bromegrass and alfalfa. For bromegrass I, all strains tested (B34b, 23, D16f, D31d, D15d, and D43e) degraded a considerable amount of pectin and, with the exception of B34b, utilized most of what was degraded. Similar, but lower, results were obtained with bromegrass II, except for the two strains of B. ruminicola, 23 and D31d, which were unable to degrade and utilize pectin from this forage. All strains were able to degrade and utilize pectin from both maturity stages of alfalfa; however, values were considerably lower for strains 23 and D31d. Synergism studies, in which a limited utilizing strain, B34b, was combined with the limited degrading strain, D31d, resulted in a slight increase in degradation and a very marked increase in utilization of the pectin in all four forages. Similar results were obtained on both alfalfa substrates with a combination of strains B34b and D16f; however, no increases were observed with this combination on bromegrass.


Conceptual clustering in knowledge organization.
Knowledge organization is a very important step in building an expert system. The problem is how to organize knowledge into a conceptual structure and thus make it complete, concise, and consistent. In this paper, concepts used in knowledge description are divided into tangible ones and intermediate ones depending on whether or not they appear in the input or the output of the system. Intermediate concepts and their relationships with tangible concepts are subjected to changes. A distance measure for rules and an algorithm for conceptual clustering are described. New intermediate concepts are generated using this algorithm. A few new concepts may replace a large number of old relationships and also generate new rules for the system. An experiment on traditional Chinese medicine shows that the proposed method produces results similar to those generated by experts.


Use of ER/PR/HER2 subtypes in conjunction with the 2007 St Gallen Consensus Statement for early breast cancer.
The 2007 St Gallen international expert consensus statement describes three risk categories and provides recommendations for treatment of early breast cancer. The set of recommendations on how to best treat primary breast cancer is recognized and used by clinicians worldwide. We now examine the variability of five-year survival of the 2007 St Gallen Risk Classifications utilizing the ER/PR/HER2 subtypes. Using the population-based California Cancer Registry, 114,786 incident cases of Stages 1-3 invasive breast cancer diagnosed between 2000 and 2006 were identified. Cases were assigned to Low, Intermediate, or High Risk categories. Five-year-relative survival was computed for the three St Gallen risk categories and for the ER/PR/HER2 subtypes for further differentiation. There were 9,124 (13%) cases classified as Low Risk, 44,234 (65%) cases as Intermediate Risk, and 14,340 (21%) as High Risk. Within the Intermediate Risk group, 33,735 (76%) were node-negative (Intermediate Risk 2) and 10,499 (24%) were node-positive (Intermediate Risk 3). For the High Risk group, 6,149 (43%) had 1 to 3 positive axillary lymph nodes (High Risk 4) and 8,191 (57%) had four or more positive lymph nodes (High Risk 5). Using five-year relative survival as the principal criterion, we found the following: a) There was very little difference between the Low Risk and Intermediate Risk categories; b) Use of the ER/PR/HER2 subtypes within the Intermediate and High Risk categories separated each into a group with better five-year survival (ER-positive) and a group with worse survival (ER-negative), irrespective of HER2-status; c) The heterogeneity of the High Risk category was most evident when one examined the ER/PR/HER2 subtypes with four or more positive axillary lymph nodes; (d) HER2-positivity did not always translate to worse survival, as noted when one compared the triple positive subtype (ER+/PR+/HER2+) to the triple negative subtype (ER-/PR-/HER2-); and (e) ER-negativity appeared to be a stronger predictor of poor survival than HER2-positivity. The use of ER/PR/HER2 subtype highlights the marked heterogeneity of the Intermediate and High Risk categories of the 2007 St Gallen statements. The use of ER/PR/HER2 subtypes and correlation with molecular classification of breast cancer is recommended.


Carbon metabolic pathways in phototrophic bacteria and their broader evolutionary implications.
Photosynthesis is the biological process that converts solar energy to biomass, bio-products, and biofuel. It is the only major natural solar energy storage mechanism on Earth. To satisfy the increased demand for sustainable energy sources and identify the mechanism of photosynthetic carbon assimilation, which is one of the bottlenecks in photosynthesis, it is essential to understand the process of solar energy storage and associated carbon metabolism in photosynthetic organisms. Researchers have employed physiological studies, microbiological chemistry, enzyme assays, genome sequencing, transcriptomics, and (13)C-based metabolomics/fluxomics to investigate central carbon metabolism and enzymes that operate in phototrophs. In this report, we review diverse CO(2) assimilation pathways, acetate assimilation, carbohydrate catabolism, the tricarboxylic acid cycle and some key, and/or unconventional enzymes in central carbon metabolism of phototrophic microorganisms. We also discuss the reducing equivalent flow during photoautotrophic and photoheterotrophic growth, evolutionary links in the central carbon metabolic network, and correlations between photosynthetic and non-photosynthetic organisms. Considering the metabolic versatility in these fascinating and diverse photosynthetic bacteria, many essential questions in their central carbon metabolism still remain to be addressed.


Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond.
There is abundant evidence that the endothelium plays a crucial role in the maintenance of vascular tone and structure. One of the major endothelium-derived vasoactive mediators is nitric oxide (NO), an endogenous messenger molecule formed in healthy vascular endothelium from the amino acid precursor L-arginine. Endothelial dysfunction is caused by various cardiovascular risk factors, metabolic diseases, and systemic or local inflammation. One mechanism that explains the occurrence of endothelial dysfunction is the presence of elevated blood levels of asymmetric dimethylarginine (ADMA)--an L-arginine analogue that inhibits NO formation and thereby can impair vascular function. Supplementation with L-arginine has been shown to restore vascular function and to improve the clinical symptoms of various diseases associated with vascular dysfunction.


Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress.
A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain-Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.2 km/day × 3 weeks) prior to P2-antigen induction of EAN. Sedentary rats developed a monophasic course of EAN beginning on postimmunization day 12.3 ± 0.2 and reaching peak severity on day 17.0 ± 0.3 (N = 12). By comparison, forced-exercise preconditioned rats exhibited a similar monophasic course but with significant (p < .05) reduction of disease severity. Analysis of popliteal lymph nodes revealed a protective effect of exercise preconditioning on leukocyte composition and egress. Compared with sedentary controls, forced exercise preconditioning promoted a sustained twofold retention of P2-antigen responsive leukocytes. The percentage distribution of pro-inflammatory (Th1) lymphocytes retained in the nodes from sedentary EAN rats (5.1 ± 0.9%) was significantly greater than that present in nodes from forced-exercise preconditioned EAN rats (2.9 ± 0.6%) or from adjuvant controls (2.0 ± 0.3%). In contrast, the percentage of anti-inflammatory (Th2) lymphocytes (7-10%) and that of cytotoxic T lymphocytes (∼20%) remained unaltered by forced exercise preconditioning. These data do not support an exercise-inducible shift in Th1:Th2 cell bias. Rather, preconditioning with forced exercise elicits a sustained attenuation of EAN severity, in part, by altering the composition and egress of autoreactive proinflammatory (Th1) lymphocytes from draining lymph nodes.


Mitochondrial proteomic analysis reveals deficiencies in oxygen utilization in medullary thick ascending limb of Henle in the Dahl salt-sensitive rat.
The renal medullary thick ascending limb (mTAL) of the Dahl salt-sensitive (SS) rat is the site of enhanced NaCl reabsorption and excess superoxide production. In the present studies we isolated mitochondria from mTAL of SS and salt-resistant control strain SS.13(BN) rats on 0.4 and 8% salt diet for 7 days and performed a proteomic analysis. Purity of mTAL and mitochondria isolations exceeded 93.6 and 55%, respectively. Using LC/MS spectral analysis techniques we identified 96 mitochondrial proteins in four biological mTAL mitochondria samples, run in duplicate, as defined by proteins with a false discovery rate <5% and scan count ≥2. Seven of these 96 proteins, including IDH2, ACADM, SCOT, Hsp60, ATPA, EFTu, and VDAC2 were differentially expressed between the two rat strains. Oxygen consumption and high-resolution respirometry analyses showed that mTAL cells and the mitochondria in the outer medulla of SS rats fed high-salt diet exhibited lower rates of oxygen utilization compared with those from SS.13(BN) rats. These studies advance the conventional proteomic paradigm of focusing exclusively upon whole tissue homogenates to a focus upon a single cell type and specific subcellular organelle. The results reveal the importance of a largely unexplored role for deficiencies of mTAL mitochondrial metabolism and oxygen utilization in salt-induced hypertension and renal medullary oxidative stress.


Summary statistics for size over space and time.
A number of studies have investigated how the visual system extracts the average feature-value of an ensemble of simultaneously or sequentially delivered stimuli. In this study we model these two processes within the unitary framework of linear systems theory. The specific feature value used in this investigation is size, which we define as the logarithm of a circle's diameter. Within each ensemble, sizes were drawn from a normal distribution. Average size discrimination was measured using ensembles of one and eight circles. These circles were presented simultaneously (display times: 13-427 ms), one at a time, or eight at a time (temporal-frequencies: 1.2-38 Hz). Thresholds for eight-item ensembles were lower than thresholds for one-item ensembles. Thresholds decreased by a factor of 1.3 for a 3,200% increase in display time, and decreased by the same factor for a 3,200% decrease in temporal frequency. Modeling and simulations show that the data are consistent with one readout of three to four items every 210 ms.


[Interaction between checkpoint genes RAD9, RAD17, RAD24, and RAD53 involved in the determination of yeast Saccharomyces cerevisiae sensitivity to ionizing radiation].
Mechanisms for genetic control of cell division cycle (checkpoint control) have been studied in most detail in yeast Saccharomyces cerevisiae. To clarify the role of checkpoint genes RAD9, RAD17, RAD24, and RAD53 in cell radioresistance, double mutants were analyzed for cell sensitivity to ionizing radiation. Double mutants carrying mutations in combination with mutation rad9delta were shown to manifest the epistatic type of interaction. Our results suggest that checkpoint genes RAD9, RAD17, RAD24, and RAD53 belong to a single epistatic group designated RAD9 and govern the same pathway. Genes RAD9 and RAD53 have a positive effect on sensitivity to gamma-radiation, whereas RAD17 and RAD24 have a negative effect. Interactions between mutations may differ when considering their sensitivity to gamma-radiation and UV light; mutations rad9delta and rad24delta were shown to manifest the additive effect in the first case and epistatic effect in the second.


[The search for strains producing new restriction endonucleases].
The search for restrictases in 154 strains belonging to 104 species of 32 genera of microorganisms has been carried out by the method of rapid toluene assay. In 10 strains the activity of endonucleases specifically fragmenting the DNA of phage lambda in the presence of Mg2+ ions has been detected. Restrictases Pae I and Pae II formed by two Pseudomonas aeruginosa strains have been identified as the true isoschizomers of restriction endonucleases Sph I and Sma I respectively. The results of the screening of restrictase-producing strains indicate that the production of restrictases is widely spread among microorganisms of the genus Bacillus.


Investigation on Imaging Features and Clinical Significance of Cardiac CT in Comprehensive Evaluation of Aortic Valve and Root before Percutaneous Aortic Valve Replacement.
Medical imaging feature analysis is the basis of medical image processing and analysis. The solution of this problem not only directly affects the successful application of computer graphics and image technology in medicine but also has important theoretical and practical significance. In this paper, the imaging characteristics and clinical significance are discussed by studying the comprehensive evaluation of aortic valve and root before aortic valve replacement. In recent years, preoperative comprehensive evaluation of the aortic valve and root has been gradually carried out. Compared with traditional methods, minimally invasive surgery brings more accurate diagnosis to patients, quick recovery and discharge after surgery, and less pain. This study retrospectively includes patients with severe aortic stenosis who underwent TAVR with routine computed tomography. Based on CT images, the determination and grouping of bicuspid aortic valve and tricuspid aortic valve were completed. Thirteen cross-sectional levels of the aorta-iliac-femoral vascular access were completed. The results showed that 3 people had stroke (17.6%) and 5 people had myocardial infarction (29.4%) during the follow-up period. Atrial fibrillation occurred in 5 patients (29.4%), permanent pacemaker implantation was performed in 1 patient (5.9%), and acute kidney injury occurred in 7 patients (41.2%). No patient died due to surgery-related causes, and the analysis of imaging features and clinical significance in the preoperative comprehensive evaluation of the aortic valve and root played a crucial role. In the training stage, the principal component analysis method was used to train the shape, and the model of the shape intensity of the aortic valve and the shape change of each principal component was obtained. The most probable aortic valve region in the target image was obtained by matching the similarity of all atlases, and the correct aortic valve segmentation was obtained by using the first level set of shape intensity. The experimental part verified the accuracy of the algorithm.


Killer instincts: natural killer cells as multifactorial cancer immunotherapy.
Natural killer (NK) cells integrate heterogeneous signals for activation and inhibition using germline-encoded receptors. These receptors are stochastically co-expressed, and their concurrent engagement and signaling can adjust the sensitivity of individual cells to putative targets. Against cancers, which mutate and evolve under therapeutic and immunologic pressure, the diversity for recognition provided by NK cells may be key to comprehensive cancer control. NK cells are already being trialled as adoptive cell therapy and targets for immunotherapeutic agents. However, strategies to leverage their naturally occurring diversity and agility have not yet been developed. In this review, we discuss the receptors and signaling pathways through which signals for activation or inhibition are generated in NK cells, focusing on their roles in cancer and potential as targets for immunotherapies. Finally, we consider the impacts of receptor co-expression and the potential to engage multiple pathways of NK cell reactivity to maximize the scope and strength of antitumor activities.


Endovascular treatment of intracranial aneurysms in Loeys-Dietz syndrome.
Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by extensive arterial aneurysms. The successful clipping of intracranial aneurysms in patients with LDS has been reported in a limited number of patients but endovascular treatment of intracranial aneurysms in LDS has never before been described. The first successful cases of endovascular management of five intracranial aneurysms in two patients with LDS are reported. The first patient was an asymptomatic 45-year-old woman with LDS and two incidentally discovered, unruptured wide necked aneurysms (6×5 mm and 4×2 mm) arising from the ophthalmic segment of the left internal carotid artery. Both aneurysms were successfully embolized via Neuroform stent assisted coiling. The second patient was an asymptomatic middle 40s woman with LDS found to have an unruptured anterior communicating artery aneurysm (7×4 mm) as well as two ophthalmic segment aneurysms (2.5×3.7 mm and 2.9×3.5 mm). All three aneurysms were successfully embolized via Neuroform stent assisted coiling in two staged procedures. There were no periprocedural complications in either patient. Long term follow-up imaging demonstrated durable embolization in all aneurysms in both patients. This is the first reported case series of endovascular management of intracranial aneurysms in the setting of LDS. The endovascular approach was safe, effective and durable in all aneurysms in both patients, and should be considered when treating patients with LDS and intracranial aneurysms.


Benefits of 8-wk Mindfulness-based Stress Reduction or Aerobic Training on Seasonal Declines in Physical Activity.
Mindfulness-based stress reduction (MBSR) and aerobic exercise training (AET) programs improve health and well-being. Exercise participation has been related to mindfulness and may be altered by MBSR training. This study aimed to compare 8 wk of MBSR, AET, and no-treatment control during the fall season on objectively measured physical activity in healthy adults. Participants (n = 66) wore an ActiGraph GT3X+ accelerometer for 7 d prerandomization and after 8 wk MBSR or AET interventions, or neither (control). Mean daily minutes (min) of moderate-to-vigorous physical activities (MVPA) were calculated along with weekly time spent in bouts of MVPA ≥10 min (MVPABouts) to assess physical activity sufficient to meet national guidelines. Groups were compared on pairwise changes in outcomes across time. Effect sizes were calculated using Cohen's d. Sufficient data (≥3 weekdays, ≥1 weekend day, and ≥10 h·d) were obtained from 49 participants (18 MBSR, 14 AET, and 17 control). Daily MVPA decreased in all groups from prerandomization to postintervention (August to November); control decreased 17.9 ± 25.7 min·d, MBSR decreased 5.7 ± 7.5 min·d, and AET decreased 7.4 ± 14.3 min·d (mean ± SD), without significant differences among the groups (all P > 0.05). MVPABouts decreased 77.3 ± 106.6 min·wk in control and 15.5 ± 37.0 min·wk in MBSR (between-group difference: P = 0.08; d = 0.86), whereas it increased by 5.7 ± 64.1 min·wk in AET (compared with control: P = 0.029; d = 0.97; compared with MBSR; P = 0.564; d = 0.29). Data from participants in a randomized controlled trial showed that although AET increases MVPA bouts compared with no treatment, MBSR training may also mitigate the influence of shorter day length and cooler weather on participation in physical activities. Future research is needed to determine how MBSR affects exercise to inform interventions. Interventions combining MBSR and exercise may be particularly successful at increasing physical activity participation.


Terahertz Analysis of CH3NH3PbI3 Perovskites Associated with Graphene and Silver Nanowire Electrodes.
In order to investigate the thermal and chemical (in)stabilities of MAPbI3 incorporated with graphene and silver nanowire (AgNW) electrodes, we employed the terahertz (THz) time-domain spectroscopy, which has a unique ability to deliver the information of electrical properties and the intermolecular bonding and crystalline nature of materials. In in situ THz spectroscopy of MAPbI3, we observed a slight blue-shift in frequency of the 2 THz phonon mode as temperatures increase across the tetragonal-cubic structural phase transition. For MAPbI3 with the graphene top electrode, no noticeable frequency shift is observed until the temperature reaches the maximum operating temperature of solar cells (85 °C). Phonon frequency shift is sensitive to the strain-induced tilt of PbI6 octahedra and our results indicate that graphene forms a stable interface with MAPbI3 and is also effective in suppression of the undesirable phase transition. Meanwhile, for MAPbI3 coupled with the AgNW bottom electrode, the THz conductivity was found to be as low as that of the MAPbI3 single layer, attributed to the chemical reaction between Ag atoms and iodide ions. The THz conductivity is greatly increased when an ultrathin Al2O3 interlayer is introduced to cover the AgNW network via the atomic layer deposition (ALD) method. ALD of Al2O3 on the AgNW surfaces at low temperature guarantees a conformal coating, which strongly affects the ohmic contacts between the NWs. Our results demonstrate the advantage of THz spectroscopy for the comprehensive analysis of thermal and chemical stabilities of perovskites associated with the electrode materials.


VanWyk-Grumbach syndrome in a male pediatric patient: A rare case report and literature review.
Primary hypothyroidism usually leads to retardation of linear growth and delay or even arrest of puberty in juvenile patients. In rare cases, pediatric patients with hypothyroidism may present with signs of VanWyk-Grumbach's syndrome (VWGS), which includes juvenile hypothyroidism, delayed bone age and pseudoprecocious puberty. The present study reported on a rare case of VWGS and other complications, including obesity, short stature, hepatomegaly and pituitary hyperplasia. In addition, a comprehensive literature review was performed to illustrate the treatment and outcome of VWGS in pediatric patients. The present study contributed to the current knowledge regarding the diagnosis and treatment of VWGS in pediatric patients.


Four years' experience in external proficiency testing programs for hair testing of drugs of abuse in Italy (HAIRVEQ) and comparison with the Society of Hair Testing program in 2005.
Since 2002, the Istituto Superiore di Sanità, Rome, Italy, in cooperation with Institut Municipal d'Investigaciò Mèdica, Barcelona, Spain, has set up an external proficiency testing program (HAIRVEQ) to evaluate reliability in hair testing for drug abuse by laboratories from the Italian National Health Service. The results obtained in the last 2 rounds (2004-2005) by 26 laboratories and the evolution of the performance in hair testing for drugs of abuse by laboratories that have participated during the whole external proficiency testing program are presented. The 3 hair samples from the last exercise (2005) were also included in the proficiency test organized by the Society of Hair Testing (SoHT) and 17 international laboratories reported results. Samples analyzed in both exercises were real hair samples from drug consumers. In 2004, 2 identical samples were sent containing cocaine and opiates. One sample was a pulverized specimen and the second one was cut in short segments. In 2005, 2 samples, one containing MDMA and another containing cocaine, were included together with one blank sample. In 2004, approximately 42% of HAIRVEQ laboratories reported an erroneous qualitative result. The scatter of quantitative results was high, although no statistical differences, except for codeine, were found between results reported for the hair specimen if pulverized or reduced in short cuts. In 2005, 47 incorrect qualitative results were reported by HAIRVEQ laboratories, whereas only 5 were informed by SoHT laboratories. Concerning quantitative results, the ones from HAIRVEQ laboratories were comparable, although more dispersed, than those reported by SoHT laboratories. The scatter in quantitative results remained quite high and similar to those of the previous years; nonetheless, an improvement in the qualitative performance was observed. Considering the few number of laboratories showing a satisfying performance, guidelines have to be provided focused on method validation and qualitative and quantitative data evaluation.


[Ultrastructure of the cerebral cortex of the rat during noise stress and alcoholic intoxication].
Ultrastructure of the rat sensomotor and acoustic cortex has been studied at a separate and joined effect of noise and alcoholic intoxication during 7 and 35 days. Certain changes in vessels, neural and glial cells specific for separate effect of noise and alcohol have been revealed. Combined application of noise and alcohol results in a more profound disorders in the cerebral vessels, with predominance of changes specific for alcoholic intoxication. Simultaneous decrease of the ultrastructural changes, peculiar for the separate effect of noise is explained as a decreasing functional loading on the cortical cells resulted from blocking synapses with alcohol.


Molecular cloning and characterization of a transcription factor for the copia retrotransposon with homology to the BTB-containing lola neurogenic factor.
By transfection experiments, we previously identified a 72-bp enhancer sequence within the Drosophila copia retrotransposon which is involved in the control of the transcription level of this mobile element in cells in culture. Gel shift assays with nuclear extracts from Drosophila hydei-derived DH-33 cells further demonstrated specific interactions of at least two nuclear factors with this enhancer sequence. Using this sequence as a probe for the screening of an expression cDNA library that we constructed from DH-33 cells RNA, we have isolated a cDNA clone encoding a 110-kDa protein with features common to those of known transcription factors; these include a two-zinc-finger motif at the C terminus, three glutamine-rich domains in the presumptive activation domain of the protein, and an N-terminal domain which shares homology with the Bric-à-brac, Tramtrack, and Broad-Complex BTB boxes. The precise DNA recognition sequence for this transcription factor has been determined by both gel shift assays and footprinting experiments with a recombinant protein made in bacteria. The functionality of the cloned element was demonstrated upon transcriptional activation of copia reporter genes, as well as of a minimal promoter coupled with the identified target DNA sequence, in cotransfection assays in cells in culture with an expression vector for the cloned factor. Southern blot and nucleotide sequence analyses revealed a related gene in Drosophila melanogaster (the lola gene) previously identified by a genetic approach as involved in axon growth and guidance. Transfection assays in cells in culture with lola gene expression vectors and in situ hybridization experiments with lola gene mutants finally provided evidence that the copia retrotransposon is regulated by this neurogenic gene in D.melanogaster, with a repressor effect in the central nervous systems of the embryos.


Liver transplantation avoided in patients with fulminant hepatic failure who received albumin dialysis with the molecular adsorbent recirculating system while on the waiting list: impact of the duration of therapy.
Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74-month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration > or =15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48-1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (> or =15 h) could be necessary to expect significant liver function improvement.


Effect of prolonged vaginal distention and sphincter transection on physiologic function of the external anal sphincter in an animal model.
To estimate the effect of prolonged vaginal distention and anal sphincter transection on contractile properties of the external anal sphincter. Young female virgin rats were randomly assigned to four treatment groups (sham, vaginal distention, transection of anal sphincter plus repair, or combined distention and transection plus repair). After 3 weeks, the anal sphincter complex was analyzed for twitch tension, maximal tetanic force, fatigue, and maximal responses to electrical field stimulation. Each sphincter was serially cross-sectioned and stained with hematoxylin and eosin to evaluate sphincter integrity. Statistical evaluation was performed using analysis of variance (Student-Newman-Keuls) and chi2 analysis. The function of a transected and repaired anal sphincter is compromised significantly after 3 weeks. Vaginal distention alone did not alter function of the sphincter. Further, prolonged vaginal distention together with sphincter transection did not result in statistically significant differences in sphincter function compared with transection alone. In an animal model, there is a major effect on external anal sphincter function in vitro 3 weeks after laceration with repair. Although prolonged vaginal distention had no significant effect alone and minimal adverse effects on the lacerated anal sphincter, laceration of the sphincter has major adverse effects on its morphology and function. II.


Homeostatic metaplasticity in the human somatosensory cortex.
Long-term potentiation (LTP) and long-term depression (LTD) are regulated by homeostatic control mechanisms to maintain synaptic strength in a physiological range. Although homeostatic metaplasticity has been demonstrated in the human motor cortex, little is known to which extent it operates in other cortical areas and how it links to behavior. Here we tested homeostatic interactions between two stimulation protocols -- paired associative stimulation (PAS) followed by peripheral high-frequency stimulation (pHFS) -- on excitability in the human somatosensory cortex and tactile spatial discrimination threshold. PAS employed repeated pairs of electrical stimulation of the right median nerve followed by focal transcranial magnetic stimulation of the left somatosensory cortex at an interstimulus interval of the individual N20 latency minus 15 msec or N20 minus 2.5 msec to induce LTD- or LTP-like plasticity, respectively [Wolters, A., Schmidt, A., Schramm, A., Zeller, D., Naumann, M., Kunesch, E., et al. Timing-dependent plasticity in human primary somatosensory cortex. Journal of Physiology, 565, 1039-1052, 2005]. pHFS always consisted of 20-Hz trains of electrical stimulation of the right median nerve. Excitability in the somatosensory cortex was assessed by median nerve somatosensory evoked cortical potential amplitudes. Tactile spatial discrimination was tested by the grating orientation task. PAS had no significant effect on excitability in the somatosensory cortex or on tactile discrimination. However, the direction of effects induced by subsequent pHFS varied with the preconditioning PAS protocol: After PAS(N20-15), excitability tended to increase and tactile spatial discrimination threshold decreased. After PAS(N20-2.5), excitability decreased and discrimination threshold tended to increase. These interactions demonstrate that homeostatic metaplasticity operates in the human somatosensory cortex, controlling both cortical excitability and somatosensory skill.


Understanding the Associations among Social Vulnerabilities, Indigenous Peoples, and COVID-19 Cases within Canadian Health Regions.
Indigenous Peoples are at an increased risk for infectious disease, including COVID-19, due to the historically embedded deleterious social determinants of health. Furthermore, structural limitations in Canadian federal government data contribute to the lack of comparative rates of COVID-19 between Indigenous and non-Indigenous people. To make visible Indigenous Peoples' experiences in the public health discourse in the midst of COVID-19, this paper aims to answer the following interrelated research questions: (1) What are the associations of key social determinants of health and COVID-19 cases among Canadian health regions? and (2) How do these relationships relate to Indigenous communities? As both proximal and distal social determinants of health conjointly contribute to COVID-19 impacts on Indigenous health, this study used a unique dataset assembled from multiple sources to examine the associations among key social determinants of health characteristics and health with a focus on Indigenous Peoples. We highlight key social vulnerabilities that stem from systemic racism and that place Indigenous populations at increased risk for COVID-19. Many Indigenous health issues are rooted in the historical impacts of colonization, and partially invisible due to systemic federal underfunding in Indigenous communities. The Canadian government must invest in collecting accurate, reliable, and disaggregated data on COVID-19 case counts for Indigenous Peoples, as well as in improving Indigenous community infrastructure and services.


Aedes (Stegomyia) aegypti in the continental United States: a vector at the cool margin of its geographic range.
After more than a half century without recognized local dengue outbreaks in the continental United States, there were recent outbreaks of autochthonous dengue in the southern parts of Texas (2004-2005) and Florida (2009-2011). This dengue reemergence has provoked interest in the extent of the future threat posed by the yellow fever mosquito, Aedes (Stegomyia) aegypti (L.), the primary vector of dengue and yellow fever viruses in urban settings, to human health in the continental United States. Ae. aegypti is an intriguing example of a vector species that not only occurs in the southernmost portions of the eastern United States today but also is incriminated as the likely primary vector in historical outbreaks of yellow fever as far north as New York, Philadelphia, and Boston, from the 1690s to the 1820s. For vector species with geographic ranges limited, in part, by low temperature and cool range margins occurring in the southern part of the continental United States, as is currently the case for Ae. aegypti, it is tempting to speculate that climate warming may result in a northward range expansion (similar to that seen for Ixodes tick vectors of Lyme borreliosis spirochetes in Scandinavia and southern Canada in recent decades). Although there is no doubt that climate conditions directly impact many aspects of the life history of Ae. aegypti, this mosquito also is closely linked to the human environment and directly influenced by the availability of water-holding containers for oviposition and larval development. Competition with other container-inhabiting mosquito species, particularly Aedes (Stegomyia) albopictus (Skuse), also may impact the presence and local abundance of Ae. aegypti. Field-based studies that focus solely on the impact of weather or climate factors on the presence and abundance of Ae. aegypti, including assessments of the potential impact of climate warming on the mosquito's future range and abundance, do not consider the potential confounding effects of socioeconomic factors or biological competitors for establishment and proliferation of Ae. aegypti. The results of such studies therefore should not be assumed to apply in areas with different socioeconomic conditions or composition of container-inhabiting mosquito species. For example, results from field-based studies at the high altitude cool margins for Ae. aegypti in Mexico's central highlands or the Andes in South America cannot be assumed to be directly applicable to geographic areas in the United States with comparable climate conditions. Unfortunately, we have a very poor understanding of how climatic drivers interact with the human landscape and biological competitors to impact establishment and proliferation of Ae. aegypti at the cool margin of its range in the continental United States. A first step toward assessing the future threat this mosquito poses to human health in the continental United States is to design and conduct studies across strategic climatic and socioeconomic gradients in the United States (including the U.S.-Mexico border area) to determine the permissiveness of the coupled natural and human environment for Ae. aegypti at the present time. This approach will require experimental studies and field surveys that focus specifically on climate conditions relevant to the continental United States. These studies also must include assessments of how the human landscape, particularly the impact of availability of larval developmental sites and the permissiveness of homes for mosquito intrusion, and the presence of other container-inhabiting mosquitoes that may compete with Ae. aegypti for larval habitat affects the ability of Ae. aegypti to establish and proliferate. Until we are armed with such knowledge, it is not possible to meaningfully assess the potential for climate warming to impact the proliferation potential for Ae. aegypti in the United States outside of the geographic areas where the mosquito already is firmly established, and even less so for dengue virus transmission and dengue disease in humans.


Morbidity and medicine prescriptions in a nationwide Danish population of patients diagnosed with polycystic ovary syndrome.
The prevalence of type 2 diabetes is increased in polycystic ovary syndrome (PCOS), but the prevalence of other diseases is not clarified. We aimed to investigate morbidity and medicine prescriptions in PCOS. A National Register-based study. Patients with PCOS (PCOS Denmark and an embedded cohort; PCOS Odense University Hospital (OUH)) and one control population. Premenopausal women with PCOS underwent clinical and biochemical examination (PCOS OUH, n=1217). PCOS Denmark (n=19 199) included women with PCOS in the Danish National Patient Register. Three age-matched controls were included per patient (n=57 483). Diagnosis codes and filled prescriptions. The mean (range) age of the PCOS Denmark group and controls was 30.6 (12-60) years. Patients in PCOS Denmark had higher Charlson index, higher prevalence of diabetes, dyslipidemia, and hypertension than controls. PCOS was associated with a two times increased risk of stroke and thrombosis, whereas the risk of other cardiovascular diseases was not increased. Thyroid disease, asthma, migraine, and depression were more prevalent in PCOS Denmark vs controls, whereas fractures were rarer. Infertility was increased in patients compared with controls, but the mean number of births was higher in PCOS. Medicine prescriptions within all diagnosis areas were significantly higher in PCOS patients than in controls.In PCOS OUH, polycystic ovaries (PCO) and irregular menses were associated with a more adverse metabolic risk profile, but individual Rotterdam criteria were not associated with cardiometabolic diagnoses. Cardiometabolic and psychiatric morbidity were significantly increased in a Danish population with PCOS. Medical diseases are frequent also in young patients with PCOS.


Characterizing pregnancy losses in Bos indicus beef females receiving a fixed-timed artificial insemination protocol.
This experiment evaluated pregnancy losses from day 30 of gestation to calving in Bos indicus females, and evaluated if serum haptoglobin concentrations during early gestation impacts subsequent pregnancy losses. A total of 4926 Nelore females were used, being 1802 nulliparous heifers inseminated as yearlings (precocious heifers), 1356 nulliparous heifers inseminated at 24 months of age (conventional heifers), 887 suckling primiparous cows, and 881 suckling multiparous cows. Cows were assigned to an ovulation synchronization + fixed-time artificial insemination (FTAI) protocol from day -11 to 0 of the experiment. Pregnancy status was verified using transrectal ultrasonography on days 30 and 60 after FTAI, via transrectal palpation on day 150 after FTAI, and according to calf birth. Blood samples were collected from all animals diagnosed pregnant on day 30 after FTAI, and analyzed for serum concentrations of haptoglobin and pregnancy associated glycoproteins (PAG). Pregnancy loss was greater (P < 0.01) from day 60-150 of gestation (10.2 %) compared with day 30-60 of gestation (6.0 %) and with day 150 of gestation to calving (7.4 %), and differed (P = 0.04) between these latter two periods. Pregnancy loss from day 30-60 of gestation did not differ (P = 0.26) among parities, whereas total pregnancy losses (day 30 to calving) were greater (P < 0.01) in precocious (28.4 %) and conventional (27.1 %) heifers compared with primiparous (16.4 %) and multiparous (13.0 %) cows. Serum PAG concentrations on day 30 after FTAI were less (P ≤ 0.03) in cows that lost the pregnancy (5.63 ng/mL) from day 30-60 of gestation, as well as those that lost the pregnancy from day 30 to calving (8.59 ng/mL) compared with cohorts that maintained the pregnancy (9.39 and 9.32 ng/mL, respectively). No differences in serum PAG concentrations on day 30 after FTAI were noted (P ≥ 0.23) according to pregnancy losses from day 60 to calving. Serum haptoglobin concentration on day 30 after FTAI also did not differ (P ≥ 0.48) between cows that maintained or lost the pregnancy. This experiment provides novel information about pregnancy losses after day 30 of gestation in B. indicus cattle, with most losses occurring as fetal mortality and not affected by systemic inflammation during early gestation. Pregnancy losses were nearly doubled in precocious and conventional heifers compared with parous cows, demonstrating the relevance of this reproductive failure to B. indicus replacement heifers.


Neural changes when actions change: adaptation of strong and weak expectations.
Repeated experiences with an event create the expectation that subsequent events will expose an analog structure. These spontaneous expectations rely on an internal model of the event that results from learning. But what happens when events change? Do experience-based internal models get adapted instantaneously, or is model adaptation a function of the solidity of, i.e., familiarity with, the corresponding internal model? The present fMRI study investigated the effects of model solidity on model adaptation in an action observation paradigm. Subjects were made acquainted with a set of action movies that displayed an altered script when encountered again in the scanning session. We found model adaptation to result in an attenuation of the premotor-parietal network for action observation. Model solidity was found to modulate activation in the parahippocampal gyrus and the anterior cerebellar lobules, where increased solidity correlated with activity increase. Finally, the comparison between early and late stages of learning indicated an effect of model solidity on adaptation rate. This contrast revealed the involvement of a fronto-mesial network of Brodmann area 10 and the ACC in those states of learning that were signified by high model solidity, no matter if the memorized original or the altered action model was the more solid component. Findings suggest that the revision of an internal model is dependent on its familiarity. Unwarranted adaptations, but also perseverations may thus be prevented.


[Nutritional and metabolic aspects of neurological diseases].
The central nervous system regulates food intake, homoeostasis of glucose and electrolytes, and starts the sensations of hunger and satiety. Different nutritional factors are involved in the pathogenesis of several neurological diseases. Patients with acute neurological diseases (traumatic brain injury, cerebral vascular accident hemorrhagic or ischemic, spinal cord injuries, and cancer) and chronic neurological diseases (Alzheimer's Disease and other dementias, amyotrophic lateral sclerosis, Parkinson's Disease) increase the risk of malnutrition by multiple factors related to nutrient ingestion, abnormalities in the energy expenditure, changes in eating behavior, gastrointestinal changes, and by side effects of drugs administered. Patients with acute neurological diseases have in common the presence of hyper metabolism and hyper catabolism both associated to a period of prolonged fasting mainly for the frequent gastrointestinal complications, many times as a side effect of drugs administered. During the acute phase, spinal cord injuries presented a reduction in the energy expenditure but an increase in the nitrogen elimination. In order to correct the negative nitrogen balance increase intakes is performed with the result of a hyper alimentation that should be avoided due to the complications resulting. In patients with chronic neurological diseases and in the acute phase of cerebrovascular accident, dysphagia could be present which also affects intakes. Several chronic neurological diseases have also dementia, which lead to alterations in the eating behavior. The presence of malnutrition complicates the clinical evolution, increases muscular atrophy with higher incidence of respiratory failure and less capacity to disphagia recuperation, alters the immune response with higher rate of infections, increases the likelihood of fractures and of pressure ulcers, increases the incapacity degree and is an independent factor to increase mortality. The periodic nutritional evaluation due to the evolutionary changes should be part of the treatment. At the same time to know the metabolic and nutritional characteristics is important to be able to prevent and treat early the possible side effects. If nutritional support is indicated, the enteral route is the route of choice although some times, mainly in critical patients, parentral nutrition is necessary to ensure the administration of the required nutrients.


The cost of male aggression and polygyny in California sea lions (Zalophus californianus).
In polygynous mating systems, males often increase their fecundity via aggressive defense of mates and/or resources necessary for successful mating. Here we show that both male and female reproductive behavior during the breeding season (June-August) affect female fecundity, a vital rate that is an important determinant of population growth rate and viability. By using 4 years of data on behavior and demography of California sea lions (Zalophus californianus), we found that male behavior and spatial dynamics--aggression and territory size--are significantly related to female fecundity. Higher rates of male aggression and larger territory sizes were associated with lower estimates of female fecundity within the same year. Female aggression was significantly and positively related to fecundity both within the same year as the behavior was measured and in the following year. These results indicate that while male aggression and defense of territories may increase male fecundity, such interactions may cause a reduction in the overall population growth rate by lowering female fecundity. Females may attempt to offset male-related reductions in female fecundity by increasing their own aggression-perhaps to defend pups from incidental injury or mortality. Thus in polygynous mating systems, male aggression may increase male fitness at the cost of female fitness and overall population viability.


Materials to prepare hospice families for dying in the home.
Many changes occur in the final hours of life. Family members of those dying at home need to be prepared for these changes, both to understand what is happening and to provide care. The objectives of this study were to describe (1) the written materials used by hospices to prepare families for dying in the home setting and (2) the content of such materials. Questionnaires were sent to 400 randomly selected hospices, of which 170 responded (45.3%) sending their written materials. The most frequently used publications were Gone from My Sight (n = 118 or 69.4%), Final Gifts (n = 44 or 25.9%) and Caregiving (n = 14 or 8.2%). Half (56.5%) of the hospices used other publications and a majority (n = 87 or 51.2%) used multiple publications. Materials were given to the families by nurses (78.2%) or social workers (67.6%). More than 90% of the hospices had materials that addressed the following signs of impending death: decreased fluid intake, decreased food intake, breathing pattern changes, cold extremities, mottling, increased sleeping, changes at the moment of death, audible secretions, urinary output changes, disorientation, incontinence, overall decline and restlessness. Seven signs were addressed less than 30% of the time; pain (28.2%), dyspnea (19.4%), bed-bound state (18.2%), skin changes (18.2%), vital sign changes (17.1%), surge of energy (11.8%) and mandibular breathing (5.9%). Hospice staff should know the content of the materials offered by their agency so they can verbally address the gaps between the written materials and family needs.


Design of two-dimensional zero reference codes with cross-entropy method.
We present a cross-entropy (CE)-based method for the design of optimum two-dimensional (2D) zero reference codes (ZRCs) in order to generate a zero reference signal for a grating measurement system and achieve absolute position, a coordinate origin, or a machine home position. In the absence of diffraction effects, the 2D ZRC design problem is known as the autocorrelation approximation. Based on the properties of the autocorrelation function, the design of the 2D ZRC is first formulated as a particular combination optimization problem. The CE method is then applied to search for an optimal 2D ZRC and thus obtain the desirable zero reference signal. Computer simulation results indicate that there are 15.38% and 14.29% reductions in the second maxima value for the 16x16 grating system with n(1)=64 and the 100x100 grating system with n(1)=300, respectively, where n(1) is the number of transparent pixels, compared with those of the conventional genetic algorithm.


Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis.
Change in the expression of body fluid proteins is caused by many diseases or environmental disturbances. The changes in tear proteins are also associated with various pathological eye conditions. Especially, chronic blepharitis is one of the most common conditions seen in the ophthalmologist's office. However, there are no specific clinical diagnostic tests for blepharitis, and it is difficult to treat effectively. Therefore, the aim of this study was to screen prognostic or diagnostic marker tear proteins for blepharitis and investigate pathogenesis of this disease using proteomics techniques. The tear proteins expressed in patients suffering from blepharitis (patient, n=19) and healthy volunteers (control, n=27) were analyzed using the two-dimensional electrophoresis (2-DE) technique. The differentially expressed proteins in patients were identified with ESI-Q-TOF (electrospray-quadrupole-time-of-flight) mass spectrometry and confirmed with western blotting. Nine proteins in patient were down regulated about 50% compared to those of the control: serum albumin precursor, alpha-1 antitrypsin, lacritin precursor, lysozyme, Ig-kappa chain VIII, prolactin inducible protein (PIP/GCDFP-15), cystatin-SA III, pyruvate kinase, and an unnamed protein. The use of the two-dimensional eletrophoretic technique could give more insight into the disease-related protein expression changes in tear fluids. Our findings reveal that the composition of tear proteins in blepharitis patients is different from that of healthy subjects and may provide further insights into the pathogenesis of blepharitis.


Visual Tract Degradation in Bilateral Normal-Tension Glaucoma-Cortical Thickness Maps and Volumetric Study of Visual Pathway Areas.
The aim of the study was to evaluate changes in the central visual pathways during the early and advanced stages of bilateral normal-tension glaucoma (NTG). The studied groups constituted patients with bilateral normal-tension glaucoma of the same stage (n = 45) and age-matched healthy volunteers (n = 17). All patients underwent ophthalmic examination and examination on a 1.5 Tesla Magnetic Resonance Scanner (Optima 360, GE Healthcare). Volume and cortical thickness analyses were performed using the open-source automated software package FreeSurfer. There was a significant difference in lateral geniculate nuclei volume between the control and advanced glaucoma groups in the right hemisphere (p = 0.03) and in the left hemisphere between the early and advanced glaucoma patients (p = 0.026). The optic chiasm volume differed significantly between the control and advanced NTG groups (p = 0.0003) and between early and advanced glaucoma patients (p = 0.004). Mean cortical thickness analysis revealed a significant increase in values in the advanced glaucoma group in the right Brodmann area 17 (BA17) (p = 0.007) and right BA18 (p = 0.049) as compared to early NTG. In the left BA18 area, the mean thickness of the cortex in the early glaucoma group was significantly lower than in the control group (p = 0.03). The increase in the grey matter thickness in the V1 region with more-advanced glaucoma stages may reflect compensatory hypertrophy. Additionally, the regions of the brain early affected during glaucoma with reduced thickness were the right lateral occipital gyrus and left lingual gyrus. The most prominent change during the course of glaucoma was the increase in grey matter thickness in the right cuneus.