Bone density and body composition in newly licenced professional jockeys.
The primary objective is the description of bone mineral density (BMD) and body composition in newly licensed jockeys. One in three male, flat jockeys has a very low bone mineral density. Further research is needed to assess the short-term risk of fractures and long-term health implications of these findings. Describe bone mineral density (BMD) and body composition in entry-level male and female, flat and jump jockeys in Great Britain. Data was collected on jockeys applying for a professional jockey license between 2013 and 2015. Areal BMD at the spine, femoral neck (FN), total hip and body composition were assessed by dual-energy X-ray absorptiometry (DXA) scan. We examined differences between BMD and body composition by gender and race type (flat or jump). Volumetric bone mineral apparent density (BMAD) of the spine and FN was also calculated to account for group differences in bone size. Seventy-nine male flat jockeys (age 18.5 ± 1.9, BMI 19.0 ± 1.4), 69 male jump (age 20.7 ± 2.0, BMI 20.6 ± 1.3) and 37 female flat jockeys (age 19.3 ± 2.0, BMI 20.8 ± 1.7) took part in this study. Spine BMD Z-scores ≤-2 for male flat, male jump and female flat jockeys were 29, 13 and 2.7%, respectively. Spine BMD was lower in male than female flat jockeys (p<0.001). All BMD scores were lower in male flat compared to male jump jockeys (p<0.001). Body fat percent (BF %) was lower in male flat jockeys compared to male jump and female flat jockeys (p<0.05). Lean mass index (LMI) was lower in male flat compared to male jump jockeys (p<0.001). Male flat jockeys had a significantly lower BMD, LMI and BF% compared to jump jockeys and female flat jockeys. Male flat jockeys had lower spine BMD scores than females. Individual bone maturation may influence these findings. Further investigation into the relevance of low BMD and altered body composition on jockey health is required.


Ectopic pregnancy versus corpus luteum cyst revisited: best Doppler predictors.
To determine the best Doppler values for differentiating ectopic pregnancy from a corpus luteum cyst of pregnancy. This was a prospective study of 80 consecutive patients with the diagnosis of ectopic pregnancy. All ectopic pregnancies were diagnosed on the basis of the presence of an extra-ovarian adnexal mass on sonography and were confirmed surgically. The last menstrual period ranged from 4 to 11 weeks (mean, 6.3 weeks), and the maximal ectopic pregnancy diameter ranged from 0.7 to 5.5 cm (mean, 2.5 cm). Seventy-six ectopic pregnancies showed color vascularity, and 40 showed corpus luteum cysts with vascular walls. The highest peak systolic velocity and the lowest resistive index of the vascular ectopic pregnancies were compared with the corresponding values in the vascular corpus luteum cysts. The mean peak systolic velocity of the ectopic pregnancies was 35.4 cm/s compared with 28.4 cm/s in corpus luteum cysts, with no significant statistical difference (P = .1). The resistive index of the ectopic pregnancies ranged from 0.15 to 1.6 (mean +/- SD, 0.61 +/- 0.24) compared with 0.39 to 0.7 (mean, 0.52 +/- 0.10) in corpus luteum cysts, with a significant statistical difference (P = .003). In this cohort, a resistive index of less than 0.39 had a specificity of 100% and a positive predictive value of 100% for diagnosing ectopic pregnancy but was present in only 15% (confidence interval, 7%-23%) of ectopic pregnancies. A resistive index of greater than 0.7 had a specificity of 100% and a positive predictive value of 100% for diagnosing ectopic pregnancy and was present in 31% (confidence interval, 21%-41%) of ectopic pregnancies. Both low and high resistive indices discriminate ectopic pregnancy from a corpus luteum cyst.


Comparison of 2-Octyl Cyanoacrylate Topical Skin Adhesive and Simple Interrupted Nylon Sutures for Wound Closure in Ankle Fracture Surgery.
Multiple options are available for closure of incisions in ankle fracture surgery. The aim of our study was to compare postoperative outcomes between conventional simple interrupted nylon sutures and 2-octyl cyanoacrylate as a topical skin adhesive to close the incision after ankle fracture surgery. We retrospectively reviewed the records of 367 consecutive patients (174 simple interrupted nylon suture patients and 193 topical skin adhesive patients) who underwent operative treatment for ankle fracture between 2010 and 2015. Development of wound complications, operative time, Olerud-Molander Ankle Score (OMAS), and patient satisfaction with the wound were compared. The demographics between the 2 groups were not different. There were no differences in complication rates ( P = .861), OMAS at 3 months or 12 months following surgery ( P = .897 and .646, respectively) between the 2 types of wound closure. Operative time was 9 minutes shorter when topical skin adhesive was used compared to nylon sutures ( P = .003). Patient satisfaction with their wound was significantly higher in the topical skin adhesive group than the nylon skin suture group ( P = .012). The use of 2-octyl cyanoacrylate topical skin adhesive for wound closure following ankle fracture surgery was effective, safe, and showed higher patient satisfaction compared to simple interrupted nylon sutures. Although caution should be taken because of the insufficient statistical power of complications, this method was an additional safe option for wound closure in ankle fracture surgery. Level III, retrospective comparative study.


Global mortality estimates for the 2009 Influenza Pandemic from the GLaMOR project: a modeling study.
Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries. We obtained weekly virology and underlying cause-of-death mortality time series for 2005-2009 for 20 countries covering ∼35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used these results plus ten country indicators in a multiple imputation model to project the mortality burden in all world countries. Between 123,000 and 203,000 pandemic respiratory deaths were estimated globally for the last 9 mo of 2009. The majority (62%-85%) were attributed to persons under 65 y of age. We observed a striking regional heterogeneity, with almost 20-fold higher mortality in some countries in the Americas than in Europe. The model attributed 148,000-249,000 respiratory deaths to influenza in an average pre-pandemic season, with only 19% in persons <65 y. Limitations include lack of representation of low-income countries among single-country estimates and an inability to study subsequent pandemic waves (2010-2012). We estimate that 2009 global pandemic respiratory mortality was ∼10-fold higher than the World Health Organization's laboratory-confirmed mortality count. Although the pandemic mortality estimate was similar in magnitude to that of seasonal influenza, a marked shift toward mortality among persons <65 y of age occurred, so that many more life-years were lost. The burden varied greatly among countries, corroborating early reports of far greater pandemic severity in the Americas than in Australia, New Zealand, and Europe. A collaborative network to collect and analyze mortality and hospitalization surveillance data is needed to rapidly establish the severity of future pandemics. Please see later in the article for the Editors' Summary.


Is love passion an addictive disorder?
Inquiry regarding the relationship between passionate love and addiction has long been a topic of intense debate. Recent advances in neurobiology now allow for an examination between these two states. After describing the clinical distinctions between "love passion," "love addiction," and "sex addiction," we compare clinical, neuropsychological, neurobiological, and neuroimaging data on love, passion, pathological gambling (PG) and substance dependence. There are no recognized definitions or diagnostic criteria for "love addiction," but its phenomenology has some similarities to substance dependence: euphoria and unrestrained desire in the presence of the love object or associated stimuli (drug intoxication); negative mood, anhedonia, and sleep disturbance when separated from the love object (drug withdrawal); focussed attention on and intrusive thoughts about the love object; and maladaptive or problematic patterns of behavior (love relation) leading to clinically significant impairment or distress, with pursuit despite knowledge of adverse consequences. Limited animal and human studies suggest that brain regions (e.g., insula, anterior cingulated [ACC], orbitofrontal [OFC]) and neurotransmitters (dopamine) that mediate substance dependence may also be involved with love addiction (as for PG). Ocytocin (OT), which is implicated in social attachment and mating behavior, may also be involved in substance dependence. There are no data on the epidemiology, genetics, co-morbidity, or treatment of love addiction. There are currently insufficient data to place some cases of "love passion" within a clinical disorder, such as "love addiction," in an official diagnostic nomenclature or to firmly classify it as a behavioral addiction or disorder of impulse control. Further clinical and scientific studies are needed to improve our understanding and treatment of this condition. For these studies, we propose new criteria for evaluating addiction to love.


Effects on the structure of Arctic ecosystems in the short- and long-term perspectives.
Species individualistic responses to warming and increased UV-B radiation are moderated by the responses of neighbors within communities, and trophic interactions within ecosystems. All of these responses lead to changes in ecosystem structure. Experimental manipulation of environmental factors expected to change at high latitudes showed that summer warming of tundra vegetation has generally led to smaller changes than fertilizer addition. Some of the factors manipulated have strong effects on the structure of Arctic ecosystems but the effects vary regionally, with the greatest response of plant and invertebrate communities being observed at the coldest locations. Arctic invertebrate communities are very likely to respond rapidly to warming whereas microbial biomass and nutrient stocks are more stable. Experimentally enhanced UV-B radiation altered the community composition of gram-negative bacteria and fungi, but not that of plants. Increased plant productivity due to warmer summers may dominate food-web dynamics. Trophic interactions of tundra and sub-Arctic forest plant-based food webs are centered on a few dominant animal species which often have cyclic population fluctuations that lead to extremely high peak abundances in some years. Population cycles of small rodents and insect defoliators such as the autumn moth affect the structure and diversity of tundra and forest-tundra vegetation and the viability of a number of specialist predators and parasites. Ice crusting in warmer winters is likely to reduce the accessibility of plant food to lemmings, while deep snow may protect them from snow-surface predators. In Fennoscandia, there is evidence already for a pronounced shift in small rodent community structure and dynamics that have resulted in a decline of predators that specialize in feeding on small rodents. Climate is also likely to alter the role of insect pests in the birch forest system: warmer winters may increase survival of eggs and expand the range of the insects. Insects that harass reindeer in the summer are also likely to become more widespread, abundant and active during warmer summers while refuges for reindeer/caribou on glaciers and late snow patches will probably disappear.


Improving binding affinity and stability of peptide ligands by substituting glycines with D-amino acids.
Improving the binding affinity and/or stability of peptide ligands often requires testing of large numbers of variants to identify beneficial mutations. Herein we propose a type of mutation that promises a high success rate. In a bicyclic peptide inhibitor of the cancer-related protease urokinase-type plasminogen activator (uPA), we observed a glycine residue that has a positive ϕ dihedral angle when bound to the target. We hypothesized that replacing it with a D-amino acid, which favors positive ϕ angles, could enhance the binding affinity and/or proteolytic resistance. Mutation of this specific glycine to D-serine in the bicyclic peptide indeed improved inhibitory activity (1.75-fold) and stability (fourfold). X-ray-structure analysis of the inhibitors in complex with uPA showed that the peptide backbone conformation was conserved. Analysis of known cyclic peptide ligands showed that glycine is one of the most frequent amino acids, and that glycines with positive ϕ angles are found in many protein-bound peptides. These results suggest that the glycine-to-D-amino acid mutagenesis strategy could be broadly applied.


The study of correlation between forward head posture and neck pain in Iranian office workers.
Factors such as prolonged sitting at work or improper posture of head during work may have a great role in neck pain occurrence among office employees, particularly among those who work with computers. Although some studies claim a significant difference in head posture between patients and pain-free participants, in literature the forward head posture (FHP) has not always been associated with neck pain. Since head, cervical and thoracic postures and their relation with neck pain has not been studied in Iranian office employees, the purpose of this study was to investigate the relationship between some work-related and individual factors, such as poor posture, with neck pain in the office employees. It was a cross-sectional correlation study carried out to explore the relationship between neck pain and sagittal postures of cervical and thoracic spine among office employees in forward looking position and also in a working position. Forty-six subjects without neck pain and 55 with neck pain were examined using a photographic method. Thoracic and cervical postures were measured using the high thoracic (HT) and craniovertebral (CV) angles, respectively. High thoracic and CV angles were positively correlated with the presence of neck pain only in working position (p < 0.05). In forward looking position, there was no statistically significant difference between the 2 groups (p > 0.05). Our findings have revealed that office employees had a defective posture while working and that the improper posture was more severe in the office employees who suffered from the neck pain.


Embargo on Lion Hunting Trophies from West Africa: An Effective Measure or a Threat to Lion Conservation?
The W-Arly-Pendjari (WAP) ecosystem, shared among Benin, Burkina Faso and Niger, represents the last lion stronghold of West Africa. To assess the impact of trophy hunting on lion populations in hunting areas of the WAP, we analyzed trends in harvest rates from 1999 to 2014. We also investigated whether the hunting areas with higher initial hunting intensity experienced steeper declines in lion harvest between 1999 and 2014, and whether lion densities in hunting areas were lower than in national parks. Lion harvest rate remained overall constant in the WAP. At initial hunting intensities below 1.5 lions/1000km2, most hunting areas experienced an increase in lion harvest rate, although that increase was of lower magnitude for hunting areas with higher initial hunting intensity. The proportion of hunting areas that experienced a decline in lion harvest rate increased at initial hunting intensities above 1.5 lions/1000km2. In 2014, the lion population of the WAP was estimated with a spoor count at 418 (230-648) adults and sub-adult individuals, comparable to the 311 (123-498) individuals estimated in the previous 2012 spoor survey. We found no significant lion spoor density differences between national parks and hunting areas. Hunting areas with higher mean harvest rates did not have lower lion densities. The ratio of large adult males, females and sub-adults was similar between the national parks and the hunting areas. These results suggested that the lion population was not significantly affected by hunting in the WAP. We concluded that a quota of 1 lion/1000km2 would be sustainable for the WAP. Based on our results, an import embargo on lion trophies from the WAP would not be justified. It could ruin the incentive of local actors to conserve lions in hunting areas, and lead to a drastic reduction of lion range in West Africa.


An examination of resveratrol's mechanisms of action in human tissue: impact of a single dose in vivo and dose responses in skeletal muscle ex vivo.
The current study tested the hypothesis that a single, moderate dose of RSV would activate the AMPK/SIRT1 axis in human skeletal muscle and adipose tissue. Additionally, the effects of RSV on mitochondrial respiration in PmFBs were examined. Eight sedentary men (23.8±2.4 yrs; BMI: 32.7±7.1) reported to the lab on two occasions where they were provided a meal supplemented with 300 mg of RSV or a placebo. Blood samples, and a muscle biopsy were obtained in the fasted state and again, with the addition of an adipose tissue biopsy, two hours post-prandial. The effect of RSV on mitochondrial respiration was examined in PmFBs taken from muscle biopsies from an additional eight men (23.4±5.4 yrs; BMI: 24.4±2.8). No effect of RSV was observed on nuclear SIRT1 activity, acetylation of p53, or phosphorylation of AMPK, ACC or PKA in either skeletal muscle or adipose tissue. A decrease in post absorptive insulin levels was accompanied by elevated skeletal muscle phosphorylation of p38 MAPK, but no change in either skeletal muscle or adipose tissue insulin signalling. Mitochondrial respiration in PmFBs was rapidly inhibited by RSV at 100-300 uM depending on the substrate examined. These results question the efficacy of a single dose of RSV at altering skeletal muscle and adipose tissue AMPK/SIRT1 activity in humans and suggest that RSV mechanisms of action in humans may be associated with altered cellular energetics resulting from impaired mitochondrial ATP production.


Perceptions and experiences of patients receiving oral chemotherapy.
Although many patients prefer orally administered cancer therapy (including oral chemotherapy) because of its convenience, the shift from hospital to home-based administration creates concerns. This article explores the perceptions and experiences of oral chemotherapy users and their caregivers to assess vulnerabilities and improvement opportunities at each stage of the medication process: choosing oral chemotherapy, prescribing, dispensing, administering, and monitoring. The authors recruited 15 current and former oral chemotherapy users, as well as caregivers who administered the medications to children, to participate in one of two focus group sessions at a comprehensive cancer center. Participants largely were satisfied with oral cancer therapy but raised concerns regarding their lack of preparedness for side effects and their unfamiliarity with the possible techniques to mitigate drug toxicity. Participants also described difficulties obtaining medications through retail pharmacies. Parents of pediatric patients with cancer indicated concerns regarding their children's emotional health and correct medication administration. Participants believed that the initial prescribing encounter should have included more education, and they also wanted more frequent follow-up by healthcare practitioners. As oral cancer therapy is used more widely, oncology healthcare providers will need to create robust mechanisms to support their safe use.


Estimation of the time component in the movement of chemicals in contaminated groundwater.
For a proper analysis of the potentially causal relationship between exposure to volatile organic chemicals (VOCs) in drinking water and health events, it is essential to know T1, the time when exposure started, and C = f(T), which is the change of the VOC concentration C as a function of time T and the total accumulated exposure (TAE) to VOCs to which an individual was exposed. In the typical situation of incidentally detected pollution of groundwater, no such information is available. This paper describes the development of a method for estimating T1, C = f(T), and TAE as part of an epidemiologic study of the health effects of VOC contamination of an aquifer serving public and private wells. Pooled test results of city wells, tested periodically since 1981, provided the data base for developing a statistical model for estimating C = f(T). This model was then applied to private wells, for which the data of only one water sample were available, to retrospectively estimate their T1. The best-fitting model was a multiple linear regression equation consisting of the natural logarithm of the VOC concentration as the response variable, with the time of sampling, the distance of the wells from the source (expressed as coordinates), the well depth, and the well capacity as determinants. The TAE was calculated by integrating the area under the time-concentration curve.


A systematic analysis reveals an essential role for high-affinity iron uptake system, haemolysin and CFEM domain-containing protein in iron homoeostasis and virulence in Candida glabrata.
Iron is an essential nutrient for all living organisms and human pathogens employ a battery of factors to scavenge iron from the high-affinity iron-binding host proteins. In the present study, we have elucidated, via a candidate gene approach, major iron acquisition and homoeostatic mechanisms operational in an opportunistic human fungal pathogen Candida glabrata. Phenotypic, biochemical and molecular analysis of a set of 13 C. glabrata strains, deleted for proteins potentially implicated in iron metabolism, revealed that the high-affinity reductive iron uptake system is required for utilization of alternate carbon sources and for growth under both in vitro iron-limiting and in vivo conditions. Furthermore, we show for the first time that the cysteine-rich CFEM (common in fungal extracellular membranes) domain-containing cell wall structural protein, CgCcw14, and a putative haemolysin, CgMam3, are essential for maintenance of intracellular iron content, adherence to epithelial cells and virulence. Consistent with their roles in iron homoeostasis, mitochondrial aconitase activity was lower and higher in mutants disrupted for high-affinity iron transport, and haemolysin respectively. Additionally, we present evidence that the mitochondrial frataxin, CgYfh1, is pivotal to iron metabolism. Besides yielding insights into major in vitro and in vivo iron acquisition strategies, our findings establish high-affinity iron uptake mechanisms as critical virulence determinants in C. glabrata.


Does low-dose heparin maintain central venous access device patency?: a comparison of heparin versus saline during a period of heparin shortage.
A common problem that complicates use of central venous access devices (CVADs) is occlusion by thrombosis. Alteplase, a recombinant tissue plasminogen activator, is used to restore line patency when thrombosis occurs. Heparin flush is commonly used to prevent this complication, but the effectiveness of this practice is unclear. A recent heparin shortage allowed examination of heparin effectiveness in reducing CVAD thrombosis. A retrospective cohort study was performed by querying a pharmacy database for alteplase use for CVAD thrombosis in adult patients during periods when heparin flushes (10 units/mL) were used and when saline flushes were used instead because of a nationwide heparin shortage. The number of patients receiving alteplase, the number of doses administered, and the total amount of alteplase used were compared over 1-month intervals of heparin flush use and 1-month intervals of saline flush use. Patient days and critical care patient days were compared between these time intervals. Peripherally inserted central catheter (PICC) line placements and replacements between time periods of heparin and saline flush were also compared. Significant increases in the number of patients receiving alteplase (P = .04), the number of alteplase doses administered (P = .04), and total dose of alteplase used (P = .05) occurred during the heparin shortage. No significant differences in patient population were observed. The percentage of PICC line replacements also increased significantly (P < .05) when heparin was not available. Heparin flush (10 units/mL) decreases thrombotic occlusions of CVADs, resulting in decreased alteplase use and fewer PICC line replacements.


Identification of metabolic system parameters using global optimization methods.
The problem of estimating the parameters of dynamic models of complex biological systems from time series data is becoming increasingly important. Particular consideration is given to metabolic systems that are formulated as Generalized Mass Action (GMA) models. The estimation problem is posed as a global optimization task, for which novel techniques can be applied to determine the best set of parameter values given the measured responses of the biological system. The challenge is that this task is nonconvex. Nonetheless, deterministic optimization techniques can be used to find a global solution that best reconciles the model parameters and measurements. Specifically, the paper employs branch-and-bound principles to identify the best set of model parameters from observed time course data and illustrates this method with an existing model of the fermentation pathway in Saccharomyces cerevisiae. This is a relatively simple yet representative system with five dependent states and a total of 19 unknown parameters of which the values are to be determined. The efficacy of the branch-and-reduce algorithm is illustrated by the S. cerevisiae example. The method described in this paper is likely to be widely applicable in the dynamic modeling of metabolic networks.


The evolution of colistin resistance increases bacterial resistance to host antimicrobial peptides and virulence.
Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to Escherichia coli in the presence of key AMPs from humans and agricultural animals by increasing AMP resistance. Moreover, MCR promotes bacterial growth in human serum and increases virulence in a Galleria mellonella infection model. Our study shows how the anthropogenic use of AMPs can drive the accidental evolution of resistance to the innate immune system of humans and animals. These findings have major implications for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.


Energy and nutrient digestibility in NutriDense corn and other cereal grains fed to growing pigs.
Two experiments were conducted to measure the energy and nutrient digestibilities in NutriDense corn and other cereal grains. An additional objective was to evaluate the effect of balancing diets with AA on the values measured for DE and ME of corn varieties. In Exp. 1, 6 growing pigs were fitted with a T-cannula in the distal ileum and allotted to a 6 x 6 Latin square design to measure apparent ileal digestibility (AID) and standardized ileal digestibility (SID) values for CP and AA in NutriDense corn, yellow dent corn, barley, wheat, and sorghum. Diets based on each of the 5 cereal grains were formulated, along with a N-free diet. Results of this experiment showed that the AID for most indispensable AA were greater (P < 0.05) in NutriDense corn and wheat than in the other cereal grains. The SID for Lys in NutriDense corn (77.6%) was greater (P < 0.05) than in yellow dent corn (68.5%), and sorghum (56.9%), but not different from wheat (75.1%) and barley (71.7%). The SID for Arg and Met in NutriDense corn also were greater (P < 0.05) than in yellow dent corn (88.1 and 87.2% vs. 84.5 and 82.8%, respectively). For the remaining indispensable AA, no differences in SID between NutriDense corn and yellow dent corn were observed. For all AA, the lowest values (P < 0.05) for AID and SID were obtained for sorghum. If calculated as grams of standardized ileal digestible AA per kilogram of DM, concentrations of all indispensable AA in NutriDense corn were greater (P < 0.05) than in yellow dent corn, but barley and wheat had greater concentrations of most AA than yellow dent corn and NutriDense corn. In Exp. 2, 12 growing barrows were placed in metabolism cages, and the DE and ME of NutriDense corn and yellow dent corn were measured. Both grains were used in diets without or with crystalline AA supplementation. Each diet was fed to 6 pigs in a 2-period, changeover design. The DE and the ME in NutriDense corn (4,004 and 3,922 kcal/kg of DM, respectively) were greater (P < 0.01) than in yellow dent corn (3,878 and 3,799 kcal/kg of DM, respectively). Values for DE and ME were not affected by the addition of crystalline AA to the diets. It is concluded that NutriDense corn has a greater value than yellow dent corn in diet formulations due to increased concentrations of digestible, indispensable AA and energy. However, barley and wheat have greater concentrations, whereas sorghum has lower concentrations, of many digestible AA than NutriDense corn.


Overexpression of Lis1 in different stages of spermatogenesis does not result in an aberrant phenotype.
Previous studies showed that in the mouse mutant Lis1(GT/GT) gene trap integration in intron 2 of Lis1 gene leads to male infertility in homozygous Lis1(GT/GT) mice. We further analyzed this line and could confirm the suggested downregulation of a testis-specific Lis1 transcript in mutant animals in a quantitative manner. Moreover, we analyzed the gene trap mutation on different genetic backgrounds in incipient congenic animals and could exclude a genetic background effect. To gain further insights into the role and requirement of LIS1 in spermatogenesis, 3 transgenic lines were generated, that overexpress Lis1 under control of the testis-specific promoters hEF-1α, which is exclusively active in spermatogonial cells, PGK2, which is active in pachytene spermatocytes and following stages of spermatogenesis, and Tnp2 which is active in round spermatids and following stages of spermatogenesis, respectively. All 3 transgenic lines remained fertile and testis sections displayed no abnormalities. To overcome the infertility of Lis1(GT/GT) males, these transgenic Lis1-overexpressing animals were mated with Lis1(GT/GT) mice to generate 'rescued' Lis1(GT/GT)/Lis1(Tpos) males. 'Rescued' animals from all transgenic lines remained infertile, thus overexpression of Lis1 in different stages of spermatogenesis could not rescue the infertility phenotype of homozygous gene trap males.


Roles of growth factors during peri-implantation development.
Several growth factor ligand and receptor gene products have been shown to play roles during preimplantation mammalian development. Genes for insulin-like growth factors (IGFs), transforming growth factors (TGFs), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and receptors for insulin, IGF, PDGF, TGF alpha and epidermal growth factor (EGF) are expressed by early embryos of several species including mouse, rat, cow and sheep. Roles of growth factors during early development have been demonstrated by addition of purified growth factors to culture medium or by molecular genetic techniques that interfere with gene expression. In this way, it has been shown that successful development of the blastocyst is dependent on the action of epidermal growth factor (EGF) and leukaemia inhibitory factor (LIF). Recent experiments show that both LIF and EGF stimulate secretion of urokinase-type plasminogen activator (uPA) and gelatinase B/matrix metalloproteinase-9 (MMP-9) in day 7 mouse blastocyst outgrowths. At the same time, tissue inhibitors of MMPs (TIMPs) are also expressed by embryonic, decidual and uterine tissues during the implantation process. It appears that LIF may act directly or indirectly, by inducing the expression of other cytokines, to regulate the temporal and spatial production and activity of proteases and protease inhibitors to create a favourable environment for implantation.


Energy-Efficient Massive Data Dissemination through Vehicle Mobility in Smart Cities.
One of the main challenges of operating a smart city (SC) is collecting the massive data generated from multiple data sources (DSs) and transmitting them to the control units (CUs) for further data processing and analysis. These ever-increasing data demands require not only more and more capacity of the transmission channels but also results in resource over-provision to meet the resilience requirements, thus the unavoidable waste as a result of the data fluctuations throughout the day. In addition, the high energy consumption (EC) and carbon discharge from these data transmissions posing serious issues to the environment we live in. Therefore, to overcome the issues of intensive EC and carbon emission (CE) of massive data dissemination in SCs, we propose an energy-efficient and carbon reduction approach by using the daily mobility of the existing vehicles as an alternative communications channel to accommodate the data dissemination in SCs. To illustrate the effectiveness and efficiency of our approach, we take the Auckland City in New Zealand as an example, assuming massive data generated by various sources geographically scattered throughout the Auckland region, to the control centres located in the city. Results obtained show that our proposed approach can provide up to four times faster transferring the large volume of data by using the existing daily vehicles' mobility, than the conventional transmission network. Moreover, our proposed approach offers about 32% less EC and CE than that of conventional network transmission approach.


Is Anorexia Nervosa a Disorder of the Self? A Psychological Approach.
The debate concerning the pathogenesis and the maintaining factors of eating disorders, anorexia nervosa in particular, is ongoing especially since therapeutic interventions do not result in satisfactory and enduring rates of remission. This paper presents a model for the pathogenesis of eating disorders, based on the hypothesis of a deficiency in the development of the self. We present the theory in light of new evidence concerning the role of attachment insecurity in the development and maintenance of eating disorders. In particular, we define the self in eating disorders in a comprehensive way by taking into account recent evidence from experimental psychology and neurobiology. The paper considers the development of the self in terms of its synchronic (i.e., experienced in the moment) and diachronic (i.e., experienced as continuous over time) aspects. Both synchronic and diachronic aspects of the self are relevant to the expression of eating disorder symptoms. Further, the maturation of the self is interwoven with the development of attachment functioning from infancy to adolescence. This interplay between these developmental processes of the self and of attachment could be crucial in understanding the pathogenesis of eating disorders. The final part of the paper suggests a neurobiological link between the theory of the self in the eating disorders and the spatiotemporal functioning of the brain. Disturbances in spatiotemporal functioning may represent the neurobiological pathway by which deficiencies in the self is related to attachment functions in individuals with eating disorders.


The Minimum Effective Training Dose Required for 1RM Strength in Powerlifters.
The aim of this multi-experiment paper was to explore the concept of the minimum effective training dose (METD) required to increase 1-repetition-maximum (1RM) strength in powerlifting (PL) athletes. The METD refers to the least amount of training required to elicit meaningful increases in 1RM strength. A series of five studies utilising mixed methods, were conducted using PL athletes & coaches of all levels in an attempt to better understand the METD for 1RM strength. The studies of this multi-experiment paper are: an interview study with elite PL athletes and highly experienced PL coaches (n = 28), an interview and survey study with PL coaches and PL athletes of all levels (n = 137), two training intervention studies with intermediate-advanced PL athletes (n = 25) and a survey study with competitive PL athletes of different levels (n = 57). PL athletes looking to train with a METD approach can do so by performing ~3-6 working sets of 1-5 repetitions each week, with these sets spread across 1-3 sessions per week per powerlift, using loads above 80% 1RM at a Rate of Perceived Exertion (RPE) of 7.5-9.5 for 6-12 weeks and expect to gain strength. PL athletes who wish to further minimize their time spent training can perform autoregulated single repetition sets at an RPE of 9-9.5 though they should expect that strength gains will be less likely to be meaningful. However, the addition of 2-3 back-off sets at ~80% of the single repetitions load, may produce greater gains over 6 weeks while following a 2-3-1 squat-bench press-deadlift weekly training frequency. When utilizing accessory exercises in the context of METD, PL athletes typically utilize 1-3 accessory exercises per powerlift, at an RPE in the range of 7-9 and utilize a repetition range of ~6-10 repetitions.


Inflammatory-associated obstructions of the male reproductive tract.
A history of urogenital inflammation occurs in 5-12% of men attending infertility clinics. Usually, infection has a detrimental effect on sperm quality by reducing concentration and motility, and possibly affecting the number of morphological normal spermatozoa. In addition, infection may be the source of auto-antibodies against spermatozoa, found in about 8% of the infertile male population. In contrast to the situation in women, there is no clear evidence that male accessory gland infections can result in epididymal blockage or vassal obstruction, with the exception of genital tuberculosis. Although Chlamydia trachomatis is a well-documented source of chronic prostatitis, the infection does not seem to cause obstruction of the reproductive tract, as it does in women. If male urogenital infection causes obstruction it is most likely located at the level of the ejaculatory ducts. Chronic prostatitis has been proved to cause scarring of the prostatic and ejaculatory ducts, resulting in low seminal volume with low fructose and alpha-glucosidase. Many of these men present with severe oligozoospermia or azoospermia, normal size testis and normal gonadotrophins. We performed an excisional testicular biopsy in all men presenting with <1 million spermatozoa per millilitre and found that 39 of 78 (50%) had a normal spermatogenesis. A history of male accessory genital infection was found in 12% of the men and 10% had abnormalities found on transrectal ultrasound of the prostate (like oedema, dilatation of the seminal vesicles and ejaculatory ducts) intraprostatic calcifications and dilatation of the periprostatic venous plexus. Ejaculatory duct obstruction is a common cause of male infertility and infections are present in at least 22-50% of these men. Transurethral resection of the ejaculatory ducts may result in a significant improvement of the sperm quality and in spontaneous pregnancies in up to 25% of the couples. In case of failure sperm aspiration from the epididymis and intracytoplasmic sperm injection is the treatment of choice.


Inferior results of salvage arthrodesis after failed ankle replacement compared to primary arthrodesis.
Up to now, there has been no evidence that salvage arthrodesis would perform inferior when compared with primary ankle arthrodesis. The purpose of this study was to compare their clinical and radiographic results. A retrospective analysis was performed using 2 validated scores and assessment of radiographic union by comparing 23 patients who underwent salvage ankle arthrodesis (group SA = salvage arthrodesis) after failed total ankle replacement with 23 matched patients who received primary ankle arthrodesis (group PA = primary arthrodesis). The mean follow-up period was 38 (range 16-92) months in group SA and 56 (23-94) months in group PA. Complete union was achieved in 17 patients (74%) after a mean time of 50 (13- 114) weeks in group SA and in 16 patients (70%) after a mean time of 23 (10-115) weeks in group PA. The SF-36 score averaged 48 points (7-80) in SA and 66 points (14-94; P = .006) in group PA. In group SA the mean FFI was 57% (22-82) for pain and 71% (44-98) for function. In group PA significantly better results for pain with 34% (0-88; P = .002) and function with 48% (1-92; P = .002) were found. Salvage arthrodesis led to impaired life quality and reduced function combined with significantly higher pain when compared with primary ankle arthrodesis. These findings can be used to counsel our patients preoperatively. Level III, retrospective case series.


The Effect of Cognitive Behavioral Therapy on Marital Quality among Women.
Marital quality reflects the individual's overall evaluation of marital relationship. The aim of study was examine the effect of cognitive behavioral counseling on marital quality among women. The experimental study was a randomized clinical trial with two groups, on 198 qualified women who referred to selected health care centers in Hamadan, Iran in 2016. The intervention participants attended four 90-minute sessions of cognitive behavioral counseling. Demographic information questionnaire and marital quality scale [Revised Dyadic Adjustment Scale (RDAS)] were completed by the two groups before and after the intervention. To perform the comparisons, t test, Chi-square test and Fisher's test, Logistic Regression and covariance analysis were used. Covariance analysis or change analysis were employed. Statistical analysis was done using SPSS Software, version 21.0. The significance level was set at 5% (P<0.05). According to the results of the present study, the mean age in the control group and the intervention group was 23.58 ± 7.54 and 35.04 ± 7.91 years old, respectively. Covariance analysis was utilized to examine the marital quality scores. In this analysis, after modification of the variables of age, marital quality score of agreement and satisfaction before the intervention, and income status, the total marital quality score experienced a significant change in all dimensions (P<0.05) and the mean scores increased remarkably. Moreover, according to the cut-off point of the dimensions, the scores of all dimensions increased remarkably and the proportion of individuals with high marital quality before and after the intervention changed significantly (P<0.05). Due to the role of sexual relations in stabilizing marriage, cognitive behavioral consultation was effective in improving marital quality especially after agreement and can be used in health care centers in order to improve the relationship between couples and reduce divorce rates (Registration number: IRCT201610209014N125).


Impaired error-monitoring function in people with Internet addiction disorder: an event-related fMRI study.
Internet addiction disorder (IAD) is rapidly becoming a prevalent mental health concern around the world. The neurobiological underpinnings of IAD should be studied to unravel the potential heterogeneity. This study was set to investigate the error-monitoring ability in IAD subjects. Fifteen IAD subjects and 15 healthy controls (HC) participated in this study. Participants were asked to perform a fast Stroop task that may show error responses. Behavioral and neurobiological results in relation to error responses were compared between IAD subjects and HC. Compared to HC, IAD subjects showed increased activation in the anterior cingulate cortex (ACC) and decreased activation in the orbitofrontal cortex following error responses. Significant correlation was found between ACC activation and the Internet addiction test scores. IAD subjects show an impaired error-monitoring ability compared to HC, which can be detected by the hyperactivation in ACC in error responses.


The impact of selected water quality parameters on the inactivation of Bacillus subtilis spores by monochloramine and ozone.
Selected water quality parameters-pH, dissolved organic carbon, turbidity (NTU), and temperature-were tested for their potential effects on ozone and monochloramine inactivation of Bacillus subtilis spores. In oxidant demand-free phosphate-buffer, temperature had the strongest influence on inactivation kinetics when using ozone, pH had a smaller but significant impact on B. subtilis spore inactivation with both monochloramine and ozone. Where monochloramine was applied, modeling and experimental measurements confirmed that dichloramine levels were too low to produce significant inactivation effects under these experimental conditions. It was demonstrated that oxidant demand-free phosphate buffer may not be an adequate environmental analogue for inactivation responses in natural waters.


Miniaturized implantable sensors for in vivo localized temperature measurements in mice during cold exposure.
We report on in vivo temperature measurements performed in mice at two specific sites of interest in the animal body over a period of several hours. In particular, the aim of this work was to monitor mouse metabolism during cold exposure, and to record possible temperature differences between the body temperature measured in the abdomen and the temperature of the brown adipose tissue (BAT) situated in the interscapular area. This approach is of biological interest as it may help unravelling the question whether biochemical activation of BAT is associated with local increase in metabolic heat production. For that purpose, miniaturized thermistor sensors have been accurately calibrated and implanted in the BAT and in the abdominal tissue of mice. After 1 week of recovery from surgery, mice were exposed to cold (6 °C) for a maximum duration of 6 h and the temperature was acquired continuously from the two sensors. Control measurements with a conventional rectal probe confirmed good performance of both sensors. Moreover, two different mouse phenotypes could be identified, distinguishable in terms of their metabolic resistance to cold exposure. This difference was analyzed from the thermal point of view by computational simulations. Our simple physical model of the mouse body allowed to reproduce the global evolution of hypothermia and also to explain qualitatively the temperature difference between abdomen and BAT locations. While with our approach, we have demonstrated the importance and feasibility of localized temperature measurements on mice, further optimization of this technique may help better identify local metabolism variations.


Nutrition in cancer patients.
Many factors can modify nutritional status in cancer patients, including cachexia, nausea and vomiting, decreased caloric intake or oncologic treatments capable of determining malabsorption. Cachexia is a complex disease characterized not only by a poor intake of nutrients or starvation, but also by metabolic derangement. Nausea and vomiting may limit the nutrient intake and are most often the consequences of oncologic treatments or opioid chronic therapy. Decreased caloric intake is considered to be one of the major causes of malnutrition, although the causes of anorexia remain unclear. Malabsorption is generally attributed to the consequences of oncologic treatments reducing the gastrointestinal absorption. Biochemical measurements and immunological tests may be not reliable indicators of nutritional status in cancer patients. Therefore, medical history, physical examination, estimates of daily oral intake, weight changes and an appropriate consideration of the nutritional requirements according to the stage of disease must still be assessed. The therapeutic approaches should be individualized and realistic. Whenever possible, oral nutrition is the method of choice, with due consideration for specific dietary needs. Nausea and anorexia can be reduced by different kinds of drugs. A careful decision based on good clinical judgement is necessary before deciding to start either enteral or parenteral nutrition, to avoid a useless, costly and difficult treatment. In choosing the route for administration of nutrients, availability of and access to a functioning gastrointestinal tract, compliance and comfort of the patient, gastrointestinal toxicity due to chemotherapy or radiotherapy fields, different costs, duration and place of treatment should be considered rather than the different capacity of parenteral versus enteral nutrition. However, postoperative periods after massive intestinal resection often require prolonged parenteral nutrition. The benefits of parenteral nutrition are not often demonstrable in patients with bowel obstruction. Different ethical aspects are presented. Flexibility in attempting to meet the nutrition needs of each patient is probably the most useful guide.


African Savanna-Forest Boundary Dynamics: A 20-Year Study.
Recent studies show widespread encroachment of forest into savannas with important consequences for the global carbon cycle and land-atmosphere interactions. However, little research has focused on in situ measurements of the successional sequence of savanna to forest in Africa. Using long-term inventory plots we quantify changes in vegetation structure, above-ground biomass (AGB) and biodiversity of trees ≥10 cm diameter over 20 years for five vegetation types: savanna; colonising forest (F1), monodominant Okoume forest (F2); young Marantaceae forest (F3); and mixed Marantaceae forest (F4) in Lopé National Park, central Gabon, plus novel 3D terrestrial laser scanning (TLS) measurements to assess forest structure differences. Over 20 years no plot changed to a new stage in the putative succession, but F1 forests strongly moved towards the structure, AGB and diversity of F2 forests. Overall, savanna plots showed no detectable change in structure, AGB or diversity using this method, with zero trees ≥10 cm diameter in 1993 and 2013. F1 and F2 forests increased in AGB, mainly as a result of adding recruited stems (F1) and increased Basal Area (F2), whereas F3 and F4 forests did not change substantially in structure, AGB or diversity. Critically, the stability of the F3 stage implies that this stage may be maintained for long periods. Soil carbon was low, and did not show a successional gradient as for AGB and diversity. TLS vertical plant profiles showed distinctive differences amongst the vegetation types, indicating that this technique can improve ecological understanding. We highlight two points: (i) as forest colonises, changes in biodiversity are much slower than changes in forest structure or AGB; and (ii) all forest types store substantial quantities of carbon. Multi-decadal monitoring is likely to be required to assess the speed of transition between vegetation types.


Stereotactic body radiotherapy for prostate cancer: treatment approaches and clinical outcomes.
Extreme hypofractionation may be a radiobiologically sound strategy against prostate cancer cells with presumed low radiosensitivity (α) and high repair capacity (β) to small treatment fractions. In this case, large doses per fraction may be more effective in the tumor cell killing. Hence, the fractionation sensitivity differential (tumor/normal tissue) favors the use of hypofractionated radiotherapy (RT) as tumor α/β values are lower than the values considered for late normal-tissue morbidity. High-dose rate brachytherapy (HDR-BT) and stereotactic body RT (SBRT) are competing extreme hypofractionated treatment methods aiming to efficiently escalate the dose against prostate cancer. Focal treatment strategies to the dominant and non-dominant tumor nodules inside the prostate have been considered with both treatment approaches.The present status of SBRT for prostate cancer is presented as well as a comparative summary of the existing studies on partial prostate boost irradiation either with HDR-BT or SBRT. Extreme hypofractionation (i.e., >6 Gy/fraction) still deserves investigation in prospective trials provided that the precaution is taken to assure an homogeneous tumor dose distribution, a short overall treament time (<5 weeks), and an optimally short fraction duration.


Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study.
Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Prospective cohort study. Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.


Challenges for biophysical modeling of microstructure.
The biophysical modeling efforts in diffusion MRI have grown considerably over the past 25 years. In this review, we dwell on the various challenges along the journey of bringing a biophysical model from initial design to clinical implementation, identifying both hurdles that have been already overcome and outstanding issues. First, we describe the critical initial task of selecting which features of tissue microstructure can be estimated using a model and which acquisition protocol needs to be implemented to make the estimation possible. The model performance should necessarily be tested in realistic numerical simulations and in experimental data - adapting the fitting strategy accordingly, and parameter estimates should be validated against complementary techniques, when/if available. Secondly, the model performance and validity should be explored in pathological conditions, and, if appropriate, dedicated models for pathology should be developed. We build on examples from tumors, ischemia and demyelinating diseases. We then discuss the challenges associated with clinical translation and added value. Finally, we single out four major unresolved challenges that are related to: the availability of a microstructural ground truth, the validation of model parameters which cannot be accessed with complementary techniques, the development of a generalized standard model for any brain region and pathology, and the seamless communication between different parties involved in the development and application of biophysical models of diffusion.


Progression of colorectal cancer is associated with multiple tumor suppressor gene defects but inhibition of tumorigenicity is accomplished by correction of any single defect via chromosome transfer.
Carcinogenesis is a multistage process that has been characterized both by the activation of cellular oncogenes and by the loss of function of tumor suppressor genes. Colorectal cancer has been associated with the activation of ras oncogenes and with the deletion of multiple chromosomal regions including chromosomes 5q, 17p, and 18q. Such chromosome loss is often suggestive of the deletion or loss of function of tumor suppressor genes. The candidate tumor suppressor genes from these regions are, respectively, MCC and/or APC, p53, and DCC. In order to further our understanding of the molecular and genetic mechanisms involved in tumor progression and, thereby, of normal cell growth, it is important to determine whether defects in one or more of these loci contribute functionally in the progression to malignancy in colorectal cancer and whether correction of any of these defects restores normal growth control in vitro and in vivo. To address this question, we have utilized the technique of microcell-mediated chromosome transfer to introduce normal human chromosomes 5, 17, and 18 individually into recipient colorectal cancer cells. Additionally, chromosome 15 was introduced into SW480 cells as an irrelevant control chromosome. While the introduction of chromosome 17 into the tumorigenic colorectal cell line SW480 yielded no viable clones, cell lines were established after the introduction of chromosomes 15, 5, and 18. Hybrids containing chromosome 18 are morphologically similar to the parental line, whereas those containing chromosome 5 are morphologically distinct from the parental cell line, being small, polygonal, and tightly packed. SW480-chromosome 5 hybrids are strongly suppressed for tumorigenicity, while SW480-chromosome 18 hybrids produce slowly growing tumors in some of the animals injected. Hybrids containing the introduced chromosome 18 but was significantly reduced in several of the tumor reconstitute cell lines. Introduction of chromosome 5 had little to no effect on responsiveness, whereas transfer ot chromosome 18 restored responsiveness to some degree. Our findings indicate that while multiple defects in tumor suppressor genes seem to be required for progression to the malignant state in colorectal cancer, correction of only a single defect can have significant effects in vivo and/or in vitro.


Prism couplers in guided-wave optics: design considerations.
Two important considerations for designing coupling prisms for optical waveguides are (a) coupling the incident wave to the full range of effective indices for the modes in the waveguide and (b) the ability to observe the optically contacted area, the wet spot, between the prism and waveguide. The latter becomes a problem with high-index prisms owing to total internal reflections. Design parameters for prisms satisfying both of these requirements are derived, and numerical examples are presented for both symmetrical and right-angle rutile prisms.


Development and validation of TMJ viscoelasticity analyzer.
We developed a TMJ viscoelasticity analyzer for non-invasive evaluation of the soft tissues of the TMJ region. We used this device to measure the viscoelastic parameters, viscosity (c), elasticity (k) and mass (m), of the TMJ region for two volunteers. Experiments were performed to determine the optimum measurement conditions for the preload magnitude, head posture and clenching level. We determined measurement variability and carried out statistical analysis by analysis of variance (ANOVA). We found that the values for c and k varied significantly depending on preload magnitudes (p < 0.001). In addition, all parameters varied significantly depending on head posture. However, clenching level did not significantly affect any of the parameters. Measurement variability was below 10% for all parameters. Examination of viscoelasticity of the TMJ region provides valuable information about functional and pathological changes in the soft tissues of this area. In this study, we were able to determine the fundamental characteristics of the TMJ viscoelasticity analyzer and develop methods for examining patients with temporomandibular disorders.


Comparison of the novel compounds creatine and pyruvateon lipid and protein metabolism in broiler chickens.
The effects of pyruvate (Pyr), creatine pyruvate (Cr-Pyr) and creatine (Cr) on lipid and protein metabolism were compared in broiler chickens. A total of 400 1-day-old male birds (Aconred) were allocated to four groups, each of which included four replicates (25 birds per replicate). Treatments consisted of unsupplemented basal diet (Control), basal diet containing 2% Pyr, basal diet containing 3% Cr and basal diet containing 5% Cr-Pyr. Cr-Pyr and Pyr significantly decreased the hepatic triglyceride and serum total cholesterol concentration (P < 0.01). Cr-Pyr markedly increased the serum non-esterified fatty acid and high-density lipoprotein cholesterol concentrations (P < 0.05), whereas the expression of carnitine palmitoyl transferase I (P < 0.05) and peroxisome proliferators-activated receptor-α (P < 0.01) mRNA in the liver were both decidedly enhanced in the Cr-Pyr group. The relative leg muscle weight was higher in the Cr-Pyr group than in the control group, whereas the serum uric acid content and hepatic glutamic-oxaloacetic transaminase activity were lower in the Cr-Pyr and Cr groups (P < 0.05), respectively. Muscle insulin-like growth factor I (P < 0.05) expression was enhanced, and the myostatin (P < 0.01) mRNA level was reduced in both the Cr-Pyr and Cr groups. In addition, Cr-Pyr did not alter body weight or the feed conversion ratio. These results indicate that, compared with Pyr and Cr alone, Cr-Pyr has a bifunctional role in broiler chickens, in that it influences both lipid and protein metabolism.


Ultra-sensitive chip-based photonic temperature sensor using ring resonator structures.
Resistance thermometry provides a time-tested method for taking temperature measurements. However, fundamental limits to resistance-based approaches has produced considerable interest in developing photonic temperature sensors to leverage advances in frequency metrology and to achieve greater mechanical and environmental stability. Here we show that silicon-based optical ring resonator devices can resolve temperature differences of 1 mK using the traditional wavelength scanning methodology. An even lower noise floor of 80 μK for measuring temperature difference is achieved in the side-of-fringe, constant power mode measurement.


Heterogeneous nuclear ribonucleoprotein K supports vesicular stomatitis virus replication by regulating cell survival and cellular gene expression.
The heterogeneous nuclear ribonucleoprotein K (hnRNP K) is a member of the family of hnRNPs and was recently shown in a genome-wide small interfering RNA (siRNA) screen to support vesicular stomatitis virus (VSV) growth. To decipher the role of hnRNP K in VSV infection, we conducted studies which suggest that the protein is required for VSV spreading. Virus binding to cells, entry, and nucleocapsid uncoating steps were not adversely affected in the absence of hnRNP K, whereas viral genome transcription and replication were reduced slightly. These results indicate that hnRNP K is likely involved in virus assembly and/or release from infected cells. Further studies showed that hnRNP K suppresses apoptosis of virus-infected cells, resulting in increased cell survival during VSV infection. The increased survival of the infected cells was found to be due to the suppression of proapoptotic proteins such as Bcl-XS and Bik in a cell-type-dependent manner. Additionally, depletion of hnRNP K resulted in not only significantly increased levels of T-cell-restricted intracellular antigen 1 (TIA1) but also switching of the expression of the two isoforms of the protein (TIA1a and TIA1b), both of which inhibited VSV replication. hnRNP K was also found to support expression of several cellular proteins known to be required for VSV infection. Overall, our studies demonstrate hnRNP K to be a multifunctional protein that supports VSV infection via its role(s) in suppressing apoptosis of infected cells, inhibiting the expression of antiviral proteins, and maintaining the expression of proteins required for the virus.


Night work and postpartum depression: a national register-based cohort study.
Objective We aimed to investigate the association of night work during pregnancy with the risk of severe postpartum depression (PPD). Methods We performed a nationwide register-based cohort study of workers in all Danish public hospitals. Daily information on working hours was retrieved from the Danish Working Hour Database from January 2007 to December 2015. Pregnancies, covariates and outcome were identified from national registries for births and hospital contacts. We performed logistic regression of the risk of severe PPD in relation to the number and duration of night shifts, spells of consecutive night shifts, and short shift intervals during the first 32 pregnancy weeks. Analyses were adjusted for age, body mass index, socioeconomic status, parity, sickness absence three months prior to pregnancy, and prior diagnosis of severe depression. Results The study cohort comprised 25 009 singleton pregnancies from 19 382 workers. The majority were nurses or physicians. Overall, we did not observe an increased risk of PPD for any of the dimensions of night work analyzed. We found, however, an increased risk of PPD (adjusted odds ratio 2.08, 95% confidence interval 1.09-4.00) among women who stopped working night shifts after the first pregnancy trimester (N=3094). Conclusion Overall, our results do not support night work during pregnancy as a risk factor for severe PPD among hospital employees. However, we observed a 2-fold increased risk of PPD among women who stopped working night shifts after the first pregnancy trimester. This may reflect the influence of the healthy worker survivor effect and warrants further attention.


Laser micromachining of efficient fiber microlenses.
We present results of the use of a CO(2) waveguide laser for the reproducible fabrication of efficient microlenses on single-mode optical fibers. Short intense laser pulses are used both to melt microlens tips to specific radii and to micromachine microlenses by ablative removal of small (~1-mum(2)) areas of glass from the fiber surface. CO(2) laser heating of fiber tips results in more consistent lens curvature than the electric arc commonly used in microlens fabrication. The microlenses formed using a laser microlathe, in which spinning fibers are shaped by simultaneous cutting and heating in the pulsed CO(2) laser beam, show excellent laser-fiber coupling with losses in the 1.5-3-dB range, an improvement of more than 2 dB over coupling with standard microlenses made by the etch and melt technique.


Transgenic soybean pollen (Glycine max L.) in honey from the Yucatán peninsula, Mexico.
Using precise pollen species determination by conventional microscopic methods, accompanied by molecular genetic markers, we found bees collect GMO (genetically modified) soybean pollen and incorporate it in Yucatan honey. Honey comb samples from Las Flores, Campeche, Mexico, often contained soybean pollen. Pollen in honey was analyzed in nine samples; six contained substantial soy pollen and two tested positive for soybean GMO. Our analyses confirm field observations that honey bees, Apis mellifera, gather soybean pollen and nectar. The resultant risk for honey production in the Yucatán Peninsula and Mexico is evident in wholesale price reduction of 12% when GMO products are detected and honey consignments are rejected. Although this affects only 1% of current export honey (2011-2013) GMO soybean is an unacknowledged threat to apiculture and its economics in one of the world's foremost honey producing areas.


[Rapid increase in maximal country specific life expectancy across cohorts].
Linear increase in the best-practice (maximal among countries) life expectancy, known as the Oeppen-Vaupel line, is the most demonstrative image of longevity progress. This study is devoted to the analysis of trends in best-practice life expectancy across cohorts born in 1870 to 1950. Other than the conventional period life expectancy, cohort life expectancy measures the lifetime of real individuals from the population under consideration. Since mortality is mostly decreasing with time, period life expectancy in a given year is usually lower than cohort life expectancy for people born in the same year. The corresponding gap between period and cohort life expectancies increases with time. Our analysis is based on data for 24 developed countries from the Human Mortality Database for the period 1870 to 2008. To estimate life expectancy for non-extinct cohorts, we apply the Lee-Carter model to extrapolate mortality rates until the year 2050. The annual increase in the best-practice cohort life expectancy across cohorts born in 1870 to 1950 is 0,43 year, while the annual increment in the period life expectancy across the same range of years is equal to 0,28 year. The best-practice cohort life expectancy has increased from 53,7 years in 1870 to 83,8 years in 1950. During this time the gap between period and cohort life expectancies has increased from 1,2 to 10,3 years. Cohorts born in 1920 to 1950 will live longer than one can expect by looking at respective period mortality patterns. For these cohorts, the longest part of their additionally gained lifetime will be spent at ages 65 and older. This substantially changes the distribution of human lifetime among different stages of the life cycle.


Detailed comparison of robotic and endoscopic transaxillary thyroidectomy.
Robotic thyroidectomy is increasingly used for patients with papillary thyroid carcinoma (PTC). We compared the differences between robotic and endoscopic transaxillary thyroidectomy with regard to surgical procedures. This retrospective study enrolled 40 patients with PTC who underwent robotic hemithyroidectomy (robot group) using the Da Vinci S system and 37 patients (endoscopic group) who underwent endoscopic hemithyroidectomy. Video files of surgery for all patients were analyzed to compare the operation procedures: (flap creation, docking [only for robot group], dissection of the superior pole, dissection of the inferior pole, identification of parathyroid glands [PTGs] and the recurrent laryngeal nerve [RLN], dissection of the thyroid along the trachea, bleeding control, application of a drain, and wound closure). The duration of each procedure and the clinicopathological characteristics were analyzed. Procedure time for patients in the robot group was shorter for inferior pole dissection and for identification of the PTGs and RLN (37.5 min vs. 50.5 min, p = 0.008). Mean total operative times for the two groups were comparable (153.0 min vs. 150.2 min, p = 0.732); however, excluding the docking procedure, operation time was shorter for the robot group (133.3 min vs. 150.2 min, p = 0.038). The number of sacrificed PTGs was also significantly smaller in the robot group (0.35 ± 0.53 vs. 0.65 ± 0.68, p = 0.036). Compared to endoscopic thyroidectomy, robotic transaxillary thyroidectomy involved a shorter time for inferior pole dissection and PTGs and RLN identification; moreover, more PTGs were spared using this procedure.


No evidence for productive PERV infection of baboon cells in in vivo infection model.
The discovery that pig endogenous retroviruses are infectious for human cells in vitro lead to vehement discussions about the possible risk of infection after clinical xenotransplantation. Since PERV transmission to non-human primate cells in vitro has been observed, similar to human cells, infection studies in non-human primates should represent the best model to analyze a potential PERV transmission after xenotransplantation. However, it is still open to discussion, whether non-human primate cells can be infected productively-similar to human cells- and whether those species are suitable to analyze PERV infection risks in vivo. In vitro, only few cell types can be tested for susceptibility. We developed a pig to baboon cell transplantation model with special emphasis on B-cell effective immunosuppression, removal of anti Gal-alpha 1,3-Gal-antibodies, inhibition of the complement cascade and long term survival of transplanted cellular grafts. This model allows us to investigate in vivo, whether any baboon cell types may be permissive for productive PERV infection. The xenograft recipients were investigated for up to 535 days post transplantation. Gal-alpha 1,3-Gal-antibody and complement levels were monitored. Potential PERV transmission was analyzed, not only in PBMC, but in a variety of tissue samples as well as in serum and plasma samples by PCR, RT-PCR and by detection of RT-activity. Moreover, potential PERV specific immune responses were studied by a highly sensitive Western-Blot-assay. Despite several days of extremely low levels of Gal-alpha 1,3-Gal-antibody and complement, and despite of long term xenochimerism, no evidence for PERV infection was obtained in any of the tested tissues or in the tested serum samples. This study supplies further evidence for a low susceptibility of baboons towards productive PERV infection after xenotransplantation.


Coronary angiographic findings and outcomes in patients with sudden cardiac arrest without ST-elevation myocardial infarction: A SWEDEHEART study.
Sudden cardiac arrest (SCA) has a substantial mortality rate and the acute coronary syndrome constitutes the major cause. Post-resuscitation electrocardiogram ST-elevation SCA (STE-SCA) is a strong indication for emergency coronary angiography, but the role of early angiography and PCI in patients without ST-elevation (NSTE-SCA) remains to be established. This paper aimed to describe this patient group and evaluate the prognostic effect of early PCI in a large nationwide cohort of NSTE-SCA patients undergoing coronary angiography. Data from SCAAR (Swedish Coronary Angiography and Angioplasty Registry) and RIKS-HIA (Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) on 4308 SCA patients in Sweden between 2005 and 2016 were descriptively analyzed and related to mortality within 30-days in both unadjusted and adjusted analyses using Cox proportional hazard models. NSTE-SCA patients had more often serious comorbidities than STE-SCA patients. Among NSTE-SCA patients, 36.4% had no significant coronary artery stenosis while severe coronary stenosis (≥90%) was present in 43.9% (1271/2896). In NSTE-SCA patients with significant stenosis (≥90%), PCI was performed in 59.2% (753/1271) with an increased unadjusted 30-day mortality (40.9% vs. 32.7%; p = .011). However, after adjustments for confounders, no difference in mortality was observed (hazard ratio 1.07; 95% CI 0.84-1.36; p = .57). In resuscitated SCA patients without ST-elevation who underwent coronary angiography, this large retrospective study found severe coronary artery stenosis in 43.9% but found no clear benefit of early PCI. Prospective randomized controlled trials are needed to accurately define the role of coronary angiography and PCI in post-resuscitation care.


'Jump start' childcare-based intervention to promote physical activity in pre-schoolers: six-month findings from a cluster randomised trial.
Participation in adequate levels of physical activity during the early years is important for health and development. We report the 6-month effects of an 18-month multicomponent intervention on physical activity in early childhood education and care (ECEC) settings in low-income communities. A cluster randomised controlled trial was conducted in 43 ECEC settings in disadvantaged areas of New South Wales, Australia. Three-year-old children were recruited and assessed in the first half of 2015 with follow-up 6 months later. The intervention was guided by Social Cognitive Theory and included five components. The primary outcome was minutes per hour in total physical activity during ECEC hours measured using Actigraph accelerometers. Intention-to-treat analysis of the primary outcome was conducted using a generalized linear mixed model. A total of 658 children were assessed at baseline. Of these, 558 (85%) had valid accelerometer data (mean age 3.38y, 52% boys) and 508 (77%) had valid accelerometry data at 6-month follow-up. Implementation of the intervention components ranged from 38 to 72%. There were no significant intervention effects on mins/hr. spent in physical activity (adjusted difference = - 0.17 mins/hr., 95% CI (- 1.30 to 0.97), p = 0.78). A priori sub-group analyses showed a greater effect among overweight/obese children in the control group compared with the intervention group for mins/hr. of physical activity (2.35mins/hr., [0.28 to 4.43], p = 0.036). After six-months the Jump Start intervention had no effect on physical activity levels during ECEC. This was largely due to low levels of implementation. Increasing fidelity may result in higher levels of physical activity when outcomes are assessed at 18-months. Australian New Zealand Clinical Trials Registry ACTRN12614000597695.


Long-lived states to sustain hyperpolarized magnetization.
Major breakthroughs have recently been reported that can help overcome two inherent drawbacks of NMR: the lack of sensitivity and the limited memory of longitudinal magnetization. Dynamic nuclear polarization (DNP) couples nuclear spins to the large reservoir of electrons, thus making it possible to detect dilute endogenous substances in magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). We have designed a method to preserve enhanced ("hyperpolarized") magnetization by conversion into long-lived states (LLS). It is shown that these enhanced long-lived states can be generated for proton spins, which afford sensitive detection. Even in complex molecules such as peptides, long-lived proton states can be sustained effectively over time intervals on the order of tens of seconds, thus allowing hyperpolarized substrates to reach target areas and affording access to slow metabolic pathways. The natural abundance carbon-13 polarization has been enhanced ex situ by almost four orders of magnitude in the dipeptide Ala-Gly. The sample was transferred by the dissolution process to a high-resolution magnet where the carbon-13 polarization was converted into a long-lived state associated with a pair of protons. In Ala-Gly, the lifetime T(LLS) associated with the two nonequivalent H(alpha) glycine protons, sustained by suitable radio-frequency irradiation, was found to be seven times longer than their spin-lattice relaxation time constant (T(LLS)/T(1) = 7). At desired intervals, small fractions of the populations of long-lived states were converted into observable magnetization. This opens the way to observing slow chemical reactions and slow transport phenomena such as diffusion by enhanced magnetic resonance.


Palmitoylation of Sindbis Virus TF Protein Regulates Its Plasma Membrane Localization and Subsequent Incorporation into Virions.
Palmitoylation is a reversible, posttranslational modification that helps target proteins to cellular membranes. The alphavirus small membrane proteins 6K and TF have been reported to be palmitoylated and to positively regulate budding. 6K and TF are isoforms that are identical in their N termini but unique in their C termini due to a -1 ribosomal frameshift during translation. In this study, we used cysteine (Cys) mutants to test differential palmitoylation of the Sindbis virus 6K and TF proteins. We modularly mutated the five Cys residues in the identical N termini of 6K and TF, the four additional Cys residues in TF's unique C terminus, or all nine Cys residues in TF. Using these mutants, we determined that TF palmitoylation occurs primarily in the N terminus. In contrast, 6K is not palmitoylated, even on these shared residues. In the C-terminal Cys mutant, TF protein levels increase both in the cell and in the released virion compared to the wild type. In viruses with the N-terminal Cys residues mutated, TF is much less efficiently localized to the plasma membrane, and it is not incorporated into the virion. The three Cys mutants have minor defects in cell culture growth but a high incidence of abnormal particle morphologies compared to the wild-type virus as determined by transmission electron microscopy. We propose a model where the C terminus of TF modulates the palmitoylation of TF at the N terminus, and palmitoylated TF is preferentially trafficked to the plasma membrane for virus budding. Alphaviruses are a reemerging viral cause of arthritogenic disease. Recently, the small 6K and TF proteins of alphaviruses were shown to contribute to virulence in vivo Nevertheless, a clear understanding of the molecular mechanisms by which either protein acts to promote virus infection is missing. The TF protein is a component of budded virions, and optimal levels of TF correlate positively with wild-type-like particle morphology. In this study, we show that the palmitoylation of TF regulates its localization to the plasma membrane, which is the site of alphavirus budding. Mutants in which TF is not palmitoylated display drastically reduced plasma membrane localization, which effectively prevents TF from participating in budding or being incorporated into virus particles. Investigation of the regulation of TF will aid current efforts in the alphavirus field searching for approaches to mitigate alphaviral disease in humans.


Sex differences in brain activation to emotional stimuli: a meta-analysis of neuroimaging studies.
Substantial sex differences in emotional responses and perception have been reported in previous psychological and psychophysiological studies. For example, women have been found to respond more strongly to negative emotional stimuli, a sex difference that has been linked to an increased risk of depression and anxiety disorders. The extent to which such sex differences are reflected in corresponding differences in regional brain activation remains a largely unresolved issue, however, in part because relatively few neuroimaging studies have addressed this issue. Here, by conducting a quantitative meta-analysis of neuroimaging studies, we were able to substantially increase statistical power to detect sex differences relative to prior studies, by combining emotion studies which explicitly examined sex differences with the much larger number of studies that examined only women or men. We used an activation likelihood estimation approach to characterize sex differences in the likelihood of regional brain activation elicited by emotional stimuli relative to non-emotional stimuli. We examined sex differences separately for negative and positive emotions, in addition to examining all emotions combined. Sex differences varied markedly between negative and positive emotion studies. The majority of sex differences favoring women were observed for negative emotion, whereas the majority of the sex differences favoring men were observed for positive emotion. This valence-specificity was particularly evident for the amygdala. For negative emotion, women exhibited greater activation than men in the left amygdala, as well as in other regions including the left thalamus, hypothalamus, mammillary bodies, left caudate, and medial prefrontal cortex. In contrast, for positive emotion, men exhibited greater activation than women in the left amygdala, as well as greater activation in other regions including the bilateral inferior frontal gyrus and right fusiform gyrus. These meta-analysis findings indicate that the amygdala, a key region for emotion processing, exhibits valence-dependent sex differences in activation to emotional stimuli. The greater left amygdala response to negative emotion for women accords with previous reports that women respond more strongly to negative emotional stimuli, as well as with hypothesized links between increased neurobiological reactivity to negative emotion and increased prevalence of depression and anxiety disorders in women. The finding of greater left amygdala activation for positive emotional stimuli in men suggests that greater amygdala responses reported previously for men for specific types of positive stimuli may also extend to positive stimuli more generally. In summary, this study extends efforts to characterize sex differences in brain activation during emotion processing by providing the largest and most comprehensive quantitative meta-analysis to date, and for the first time examining sex differences as a function of positive vs. negative emotional valence. The current findings highlight the importance of considering sex as a potential factor modulating emotional processing and its underlying neural mechanisms, and more broadly, the need to consider individual differences in understanding the neurobiology of emotion.


Immune responses of the domestic fowl to Dermanyssus gallinae under laboratory conditions.
There appear to be few reports in the literature regarding the host-poultry red mite (Dermanyssus gallinae) immunological relationship, despite the negative impact D. gallinae can have on both bird welfare and egg production, as well as its potential to act as a reservoir of zoonotic infections. The current study investigated the effect of either continuous infestation (CI) for 22 days or repeated infestation (RI) for four 24-h periods 7 days apart with D. gallinae on humoral immunity (IgM and IgY) and Th1/Th2 cytokine mRNA expression in peripheral blood mononuclear cells (PBMC) compared to non-infested controls. Serum IgY levels and IgM concentration were significantly higher in CI than RI and control birds although Th1 and Th2 mRNA expression in PBMC did not differ significantly between groups. D. gallinae appeared to modify reproductive behaviour and progeny survival following successive feeding events. In the RI group, the proportion of eggs/mite was significantly higher (P < 0.05) after first infestation than later infestations while larval/nymphal mortality was significantly higher (P < 0.05) after the first two infestations than later infestations. These data suggest that D. gallinae might adopt a feeding strategy of minimal host interference while D. gallinae could determine host immune status via nymphal/larval survival rates. Further research is required to better understand the host immunomodulation or avoidance strategy of D. gallinae as well as whether the mite is able to determine host immunocompetence perhaps using progeny survival.


Observational Health Data Sciences and Informatics (OHDSI): Opportunities for Observational Researchers.
The vision of creating accessible, reliable clinical evidence by accessing the clincial experience of hundreds of millions of patients across the globe is a reality. Observational Health Data Sciences and Informatics (OHDSI) has built on learnings from the Observational Medical Outcomes Partnership to turn methods research and insights into a suite of applications and exploration tools that move the field closer to the ultimate goal of generating evidence about all aspects of healthcare to serve the needs of patients, clinicians and all other decision-makers around the world.


Clinical use of objective measures of physical activity.
With measurement of physical activity becoming more common in clinical practice, it is imperative that healthcare professionals become more knowledgeable about the different methods available to objectively measure physical activity behaviour. Objective measures do not rely on information provided by the patient, but instead measure and record the biomechanical or physiological consequences of performing physical activity, often in real time. As such, objective measures are not subject to the reporting bias or recall problems associated with self-report methods. The purpose of this article was to provide an overview of the different methods used to objectively measure physical activity in clinical practice. The review was delimited to heart rate monitoring, accelerometers and pedometers since their small size, low participant burden and relatively low cost make these objective measures appropriate for use in clinical practice settings. For each measure, strengths and weakness were discussed; and whenever possible, literature-based examples of implementation were provided.


Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial.
It is widely thought that widespread antibiotic use selects for community antibiotic resistance, though this has been difficult to prove in the setting of a community-randomized clinical trial. In this study, we used a randomized clinical trial design to assess whether macrolide resistance was higher in communities treated with mass azithromycin for trachoma, compared to untreated control communities. In a cluster-randomized trial for trachoma control in Ethiopia, 12 communities were randomized to receive mass azithromycin treatment of children aged 1-10 years at months 0, 3, 6, and 9. Twelve control communities were randomized to receive no antibiotic treatments until the conclusion of the study. Nasopharyngeal swabs were collected from randomly selected children in the treated group at baseline and month 12, and in the control group at month 12. Antibiotic susceptibility testing was performed on Streptococcus pneumoniae isolated from the swabs using Etest strips. In the treated group, the mean prevalence of azithromycin resistance among all monitored children increased from 3.6% (95% confidence interval [CI] 0.8%-8.9%) at baseline, to 46.9% (37.5%-57.5%) at month 12 (p = 0.003). In control communities, azithromycin resistance was 9.2% (95% CI 6.7%-13.3%) at month 12, significantly lower than the treated group (p < 0.0001). Penicillin resistance was identified in 0.8% (95% CI 0%-4.2%) of isolates in the control group at 1 year, and in no isolates in the children-treated group at baseline or 1 year. This cluster-randomized clinical trial demonstrated that compared to untreated control communities, nasopharyngeal pneumococcal resistance to macrolides was significantly higher in communities randomized to intensive azithromycin treatment. Mass azithromycin distributions were given more frequently than currently recommended by the World Health Organization's trachoma program. Azithromycin use in this setting did not select for resistance to penicillins, which remain the drug of choice for pneumococcal infections. www.ClinicalTrials.gov NCT00322972. Please see later in the article for the Editors' Summary.


Lysyl hydroxylase 3 modifies lysine residues to facilitate oligomerization of mannan-binding lectin.
Lysyl hydroxylase 3 (LH3) is a multifunctional protein with lysyl hydroxylase, galactosyltransferase and glucosyltransferase activities. The LH3 has been shown to modify the lysine residues both in collagens and also in some collagenous proteins. In this study we show for the first time that LH3 is essential for catalyzing formation of the glucosylgalactosylhydroxylysines of mannan-binding lectin (MBL), the first component of the lectin pathway of complement activation. Furthermore, loss of the terminal glucose units on the derivatized lysine residues in mouse embryonic fibroblasts lacking the LH3 protein leads to defective disulphide bonding and oligomerization of rat MBL-A, with a decrease in the proportion of the larger functional MBL oligomers. The oligomerization could be completely restored with the full length LH3 or the amino-terminal fragment of LH3 that possesses the glycosyltransferase activities. Our results confirm that LH3 is the only enzyme capable of glucosylating the galactosylhydroxylysine residues in proteins with a collagenous domain. In mice lacking the lysyl hydroxylase activity of LH3, but with untouched galactosyltransferase and glucosyltransferase activities, reduced circulating MBL-A levels were observed. Oligomerization was normal, however and residual lysyl hydroxylation was compensated in part by other lysyl hydroxylase isoenzymes. Our data suggest that LH3 is commonly involved in biosynthesis of collagenous proteins and the glucosylation of galactosylhydroxylysines residues by LH3 is crucial for the formation of the functional high-molecular weight MBL oligomers.


Case report: paucity of interlobular bile ducts in Chinese children.
Sixteen Chinese children with cholestasis since early infancy were diagnosed to have paucity of interlobular bile ducts (PILBD) or its equivalent. Twelve children belonged to the syndromic group of PILBD and four children belonged to the non-syndromic group. A definite histological diagnosis of bile duct paucity was established in only two children (aged 4 and 9 months) during the first percutaneous needle biopsy. In the remaining 14 children a varying degree of bile duct destruction was evident in the follow up percutaneous or wedge liver biopsies. The evolving changes were characterized by inflammatory infiltration near or at the ductal wall, the presence of dysmorphic ductules, the degeneration of ductal epithelia and a progressive decrease of interlobular bile ducts. Of 10 children who underwent laparotomy for definite diagnosis, kasai operation was performed in two of them. In the syndromic PILBD group, all children, including two paired siblings, had at least three of five major clinical features. Hypoplasia of the extrahepatic biliary tree was found in five children and atresia of the extrahepatic bile duct was found in one. Three of six children studied were shown, by polymerase chain reaction, to have cytomegalovirus infection in the liver. This study demonstrates that bile duct paucity is a result of progressive bile duct destruction. A definitive diagnosis is difficult to make in early infancy. Thus, the careful evaluation of extrahepatic features in cholestatic children and follow-up liver biopsies are indicated. Although the pathogenetic mechanism of PILBD is unknown, bile duct destruction is the common pathway leading to paucity of bile ducts irrespective of syndromic or non-syndromic types.


An in vitro study on the antioxidant capacity of usnic acid on human erythrocytes and molecular models of its membrane.
Usnic acid (UA) has been associated with chronic diseases through its antioxidant action. Its main target is the cell membrane; however, its effect on that of human erythrocytes has been scarcely investigated. To gain insight into the molecular mechanisms of the interaction between UA and cell membranes human erythrocytes and molecular models of its membrane have been utilized. Dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) were chosen as representative of phospholipid classes located in the outer and inner monolayers of the erythrocyte membrane, respectively. Results by X-ray diffraction showed that UA produced structural perturbations on DMPC and DMPE bilayers. DSC studies have indicated that thermotropic behavior of DMPE was most strongly distorted by UA than DMPC, whereas the latter is mainly affected on the pretransition. Scanning electron (SEM) and defocusing microscopy (DM) showed that UA induced alterations to erythrocytes from the normal discoid shape to echinocytes. These results imply that UA molecules were located in the outer monolayer of the erythrocyte membrane. Results of its antioxidant properties showed that UA neutralized the oxidative capacity of HClO on DMPC and DMPE bilayers; SEM, DM and hemolysis assays demonstrated the protective effect of UA against the deleterious oxidant effects of HClO upon human erythrocytes.


The psychological effect of orphanhood in a matured HIV epidemic: an analysis of young people in Mukono, Uganda.
As the HIV pandemic progresses, the number of orphans is expected to rise. Uganda is one of the countries that has been most impacted by the pandemic. A few studies have explored the effects of orphanhood on psychological well-being; however, most of these studies have not explored potential pathways through which orphanhood could affect psychological well-being. Using a school-based sample, this study sought to examine the differences in depressive symptoms and hopelessness between orphans and non-orphans in Mukono District, Uganda. The study also explored the potential mediating role of the family environment. The study included 1500 young people from 10 randomly selected schools in Mukono Town Council. Data on school characteristics also were collected from the head teachers or their designees. Linear regression methods were used for multivariate models. We found that orphanhood was associated with psychological ill health among the males. Male double and male maternal orphans had a significantly higher level of hopelessness than their non-orphaned counterparts. Male double orphans also had more depressive symptoms, but this association was mediated by the family environment. No differences were noted between orphaned and non-orphaned females. The cause and timing of parental death was important only among the males, and loss of a parent to HIV was associated with worse psychological outcomes among the males and not the females. Lower parent/guardian connectedness, having a chronically ill adult in the household and ill treatment in residence were associated with a higher level of depression, especially among the males. The data show that the effect of orphanhood on psychological outcomes may vary by gender and type of outcome. This study also suggests an attenuated effect of orphanhood on psychological well-being among school-going youth. Programs seeking to improve psychological well-being among youth must pay attention to the family situations of these youth.