Sitting, standing and moving during work and leisure among male and female office workers of different age: a compositional data analysis.
Gendered patterns of physical activity behaviours may help explaining health inequalities between men and women. However, evidence on such patterns in the working population is sparse. This study aimed at documenting and comparing compositions of sitting, standing and moving at work and during leisure among male and female office workers of different age. Sitting (including lying), standing and moving were measured using accelerometry for, on average, four working days in 55 male and 57 female Swedish office workers. Behaviours were described in terms of time spent in four exhaustive categories: sitting in short (< 30 min) and long (≥30 min) bouts, standing, and moving. In a compositional data analysis approach, isometric log-ratios (ilr) were calculated for time sitting relative to non-sitting, time in short relative to long sitting bouts, and time in standing relative to moving. Differences between genders (men vs. women), domains (work vs. leisure), and according to age were examined for each ilr using ANOVA. At work, time spent sitting in short bouts, sitting in long bouts, standing, and moving was, on average, 29, 43, 21 and 7% among men, and 28, 38, 26 and 7% among women. Corresponding proportions during leisure were 34, 27, 27 and 13% among men and 28, 27, 32 and 13% among women. Men spent more time sitting relative to non-sitting ([Formula: see text] =0.04, p = 0.03) than women, and less time standing relative to moving ([Formula: see text] =0.07, p = 0.01). At work compared to during leisure, both genders spent more time sitting relative to non-sitting ([Formula: see text] =0.47, p < 0.01); within sitting more time was spent in long relative to short sitting bouts ([Formula: see text] =0.26, p < 0.01), and within non-sitting, more time was spent standing than moving ([Formula: see text] =0.12, p < 0.01). Older workers spent less of their non-sitting time moving than younger workers ([Formula: see text] =0.07, p = 0.01). Male office workers spent more time sitting relative to non-sitting than female workers, and more time moving relative to standing. Both genders were sitting more at work than during leisure. Older workers moved less than younger. These workers could likely benefit from interventions to reduce or break up prolonged sitting time, preferably by moving more.


Prenatal sonographic diagnosis of hypochondroplasia in a high-risk fetus.
Hypochondroplasia (HCH) is caused by mutations in the fibroblast growth factor receptor type 3 (FGFR 3). Prenatal diagnosis of HCH based exclusively on the sonographic measurements of the fetal skeleton is difficult and has not been reported. We describe a newborn infant with HCH who was born to a mother with achondroplasia (ACH) and a father with HCH. Serial sonographic measurements were recorded from 16 weeks of gestation. All measurements remained normal up to 22 weeks of gestation. At 25 weeks of gestation, the long bones began to appear shorter than expected for gestational age, while the head measurements (biparietal diameter and head circumference) remained normal. The measurements were sufficiently different to distinguish from findings in normal and achondroplastic fetuses. Our findings suggest that it is possible to distinguish the normal fetus from a fetus affected with HCH and to distinguish HCH and ACH from each other based on the sonographic measurements alone. To our knowledge, this is the first report of longitudinal sonographic measurements of HCH in the second and third trimesters.


Evaluation of Antihyperglycemic Effect of Extract of Moringa stenopetala (Baker f.) Aqueous Leaves on Alloxan-Induced Diabetic Rats.
Diabetes is a serious metabolic disorder with complications that result in significant morbidity and mortality. Current drugs used for diabetes therapy are not free from side effects and do not restore normal glucose homeostasis. Therefore, the purpose of this study is to evaluate the antidiabetic effect of Moringa stenopetala (Baker f.) aqueous leaves extract. Thirty rats of weight 90-150 gram were distributed to five groups (n= 6). Then labelled as diabetic control (DC), normal control (NC), extract treated (MS 250 and 500mg/kg), and glibenclamide treated (GL 5mg/kg). The experimental rats were induced by intra-peritoneal injection of Alloxan monohydrate at a dose of 180 mg/kg after dissolving in normal saline. Clinical biochemistry such as AST, ALT, ALP, urea, creatinine, and cholesterol, blood glucose level, histopathological and preliminary phytochemical screening were evaluated. Phytochemical tests revealed the presence of different secondary metabolites. Alkaloid, flavonoid, tannin, saponin, phytosteroids, phenols and terpenoids. Moringa stenopetala (Baker f.) leaves aqueous extract (250 and 500mg/kg) improved the body weight of rats, showed remarkable reduction in blood glucose concentration (P<0.05), and significantly decreased serum urea, creatinine, ALT, AST and ALP (P < 0.05). Levels of serum cholesterol remained unaltered in the experimental groups when compared with diabetic control. Histopathology of non-treated rats showed deterioration of insulin producing pancreas cells; nevertheless, β-cells restoration was observed due to administration of Moringa stenopetala (Baker f.) aqueous leaves extract. It is possible to conclude that oral administration of Moringa stenopetala (Baker f.) aqueous leaf extracts (250mg/kg and 500mg/kg) for 28 days showed beneficial effects on antihyperglycemia, improved body weight and Alloxan damaged pancreatic β-cells, and restored biochemical changes.


Enzyme-catalyzed crosslinking in a partly frozen state: a new way to produce supermacroporous protein structures.
In this study a new way to produce supermacroporous protein structures was investigated. Enzyme-mediated crosslinking of gelatin or casein was performed in a partly frozen state, which yielded stable, protein-based cryogels. The reaction kinetics for the formation of cryogels were found to be fairly slow, most likely due to the low temperature (-12 °C) used or due to an increased viscosity owing to the cryo-concentration taking place. The produced cryogels were characterized with regards to their physical properties and in vitro degradation. Furthermore, cryogels produced from gelatin and casein were evaluated as potential scaffolds by fibroblast cultivation to confirm their in vitro biocompatibility. Gelatin- and casein-based scaffolds both supported cell proliferation and migration through the scaffold.


Data on the expression of cellular lncRNAs in human adenovirus infected cells.
Expression of cellular long non-coding RNAs (lncRNAs) in human primary lung fibroblasts (IMR-90) during the course of adenovirus type 2 (Ad2) infection was studied by strand-specific whole transcriptome sequencing. In total, 645 cellular lncRNAs were expressed at a significant level and 398 of them were changed more than 2-fold. The changes in expression followed a distinct temporal pattern. Significantly, 80% of the changes occurred at the late phase and 80% of the de-regulated lncRNAs were up-regulated. The three largest groups of deregulated lncRNAs were 125 antisense RNAs, 111 pseudogenes and 85 long intergenic non-coding RNAs (lincRNAs). Lastly, more than 36% of lncRNAs have been shown to interact with RNA binding proteins.


The effect of abutment screw length on screw loosening in dental implants with external abutment connections after thermocycling.
The aim of this study was to investigate the effects of abutment screw length on screw loosening after thermocycling. Twenty-one grade 5 titanium (Ti) abutments were connected to grade 4 Ti implants with grade 5 Ti abutment screws. These implant/abutment screw/abutment assemblies were divided into seven groups according to the length of the abutment screw; each group included three assemblies. The screws were tightened to 30 Ncm and subjected to 2,000 thermocycles in water baths at 4°C and 60°C, with 60 seconds of immersion at each temperature. Removal torque values (RTVs) were measured before and after thermocycling, and differences in RTVs according to abutment screw length pre- and post-thermocycling were analyzed statistically. Mean RTVs before and after thermocycling were as follows: 23.0±4.4 Ncm and 25.5±0.9 Ncm for 1.4-mm-long abutment screws, 26.7±2.5 and 24.5±2.6 Ncm for 1.8-mm screws, 26.0±1.3 and 25.0±1.8 for 2.2-mm screws, 25.0±2.0 and 25.3±0.8 for 2.6-mm screws, 22.5±4.4 and 22.5±0.5 for 3.0-mm screws, 26.5±2.3 and 25.2±1.3 for 3.4-mm screws, and 25.5±4.8 and 23.2±0.8 for 3.8-mm screws, respectively. As the screw length increased, no statistically significant differences were found in the mean RTVs among the groups before or after thermocycling. Additionally, none of the groups showed significant changes in RTVs after cyclic thermal stress. Abutment screw length had no significant effect on screw loosening under thermal stress. From the results of this study, daily temperature changes in the oral cavity may have no negative influence on the integrity of an implant-abutment joint when a minimum of three and a half threads of an abutment screw are engaged.


Congenital labyrintho-tympanic fistula -- a recently recognized entity in children.
A case of congenital labyrintho-tympanic fistula is reported. The possible anatomical pathways and main clinical characteristics are discussed together with a review of the literature. Special emphasis is made for early recognition in children, of this entity without invasive forms of investigation, and the proper surgical approach via tympanotomy is described.


High performance organic light-emitting diodes employing ITO-free and flexible TiO x /Ag/Al:ZnO electrodes.
The broad application of flexible optoelectronic devices is still hampered by the lack of an ITO-free and highly flexible transparent electrode. Dielectric/metal/dielectric (DMD) transparent electrodes are promising candidates to replace ITO, especially in flexible devices due to their mechanical stability to bending, high optical transmittance and low sheet resistance (<6 Ω sq-1). This paper reports on organic light emitting diodes (OLEDs) employing a DMD electrode, specifically TiO x /Ag/Al:ZnO (doped with 2 wt% Al2O3) fabricated by sputter deposition, together with a solution-processed organic polymeric emitting layer. The electrodes were sputtered without substrate heating on rigid glass and flexible polyethylene terephthalate (PET). The results showed that the OLED devices on the DMD electrodes outperform the OLEDs on commercial ITO substrates in terms of maximum luminance as well as current efficacy. Specifically, DMD-based devices achieve up to 30% higher current efficacy on glass and up to 260% higher efficacy on PET, as compared to the ITO-based reference devices. Maximum luminance reaches up to 100 000 cd m-2 for the DMD-based OLEDs on glass and 43 000 cd m-2 for those on PET. This performance is due to the low sheet resistance of the electrodes combined with efficient light outcoupling and shows the potential of DMDs to replace ITO in optoelectronic devices. This outstanding type of optoelectronic device paves the way for the future high throughput production of flexible display and photovoltaic devices.


[Classical crossed pontine syndromes].
Definitions of classical crossed brainstem syndromes in the modern neurological literature are often inaccurate and inconsistent. As a result, different clinical syndromes are designated with the same eponym, other crossed syndromes are nearly completely forgotten. In this study, the original historical publications on the classical alternating pontine syndromes of Foville, Millard-Gubler, Raymond, Raymond-Cestan, Brissaud-Sicard, Gasperini, Grenet and Gelle were reviewed and critically analysed. Their anatomic basis and etiology, and the main publications about each syndrome were discussed. We conclude that the syndromes of Foville, Millard-Gubler, Raymond, Raymond-Cestan and Brissaud-Sicard are interpreted in their essential parts concurring to their historical descriptions. Crossed syndromes of Foville and Millard-Gubler are occasionally mixed up with each other. The syndromes in the last decades described as crossed syndromes of Gasperini and Grenet were, however, never described by Gasperini and Grenet. The existence of the Gelle's as "paralysie alterné de l'acoustique" postulated syndrome seems to be very questionable.


Do family medicine residents optimally prescribe antibiotics for common infectious conditions seen in a primary care setting?
Antimicrobial resistance is a worldwide phenomenon that leads to a significant number of unnecessary deaths and costly hospital admissions. More than 90% of antibiotic use happens in the community and of this, family physicians account for two-thirds of these prescriptions. Our study aims to determine whether family medicine residents are optimally trained in antibiotic prescribing for common infectious conditions seen in a primary care setting. This study is a secondary analysis of a prior study of antimicrobial stewardship in two urban primary care clinics in central Toronto, Ontario. A total of 1099 adult patient visits were included that involved family medicine resident trainees, seen between 2015 and 2016. The main outcome measures were resident antibiotic prescription rates for each condition and expert-recommended prescribing practices, the rate prescriptions were issued as delayed prescriptions, and the use of first-line recommended narrow-spectrum antibiotics. Compared to expert-recommended prescribing rates, family medicine residents overprescribed for uncomplicated upper respiratory tract infections (URI) (5.0% [95% CI 2.2% to 9.7%] versus 0% expert recommended) and sinusitis (44.2% [95% CI 32.8% to 55.9%] versus 11%-18% expert range), and under prescribed for pneumonia (53.5% [95% CI 37.7% to 68.8%] versus 100% expert range]). Prescribing rates were within expert recommended ranges for pharyngitis (28.6% [95% CI 16.6% to 43.3%]), bronchitis (3.6% [95% CI 0% to 18.4%]), and cystitis (79.4% [95% CI 70.6% to 86.6%]). The antibiotic prescribing practices of family medicine residents during their training programs indicated overprescribing of antibiotics for some common infection presentations. Further study of antibiotic prescribing in primary care training programs across Canada is recommended to determine if future family physicians are learning appropriate antibiotic prescribing practices.


A randomised controlled trial of opioid only versus combined opioid and non-steroidal anti inflammatory analgesics for pain relief in the first 48 hours after Caesarean section.
Post-Caesarean section pain is complex in nature, requiring a combination of pharmacological and non-pharmacological methods. Effective management of postoperative pain will reduce postoperative morbidity, hospital stay and cost. The objective of this study was to compare the clinical effectiveness and adverse effects of a combination of non-selective cyclooxygenase (COX) inhibitor (Diclofenac sodium 50 mg) and opioid (Pentazocine 60 mg) to opiod only (Pentazocine 60 mg) for pain management after Caesarean section (CS) at Aminu Kano Teaching Hospital (AKTH). This was a randomised double-blind controlled study conducted at AKTH, Kano, Nigeria. A total of 166 patients scheduled to undergo either emergency or elective Caesarean section were studied. Group I received a combination of COX inhibitor and opiod while Group II received opiod only for pain management after CS. The average age of the patients was 28.35 years (SD ± 6.426) in the group I and 26.9(SD ± 6.133) in group II. The mean parity was 3.27(SD ± 2.67) and 2.75(SD ± 2.14) while the mean gestational age at admission was 37.68(SD ± 2.69) and 38.18(SD ± 2.63) weeks in the first and second groups, respectively. Comparison of the level of pain experienced and patients satisfaction during the first 48 hours postoperatively revealed that the level of pain was statistically significantly less and patient's satisfaction significantly better in group I compared to group II (P-value 0.00001). The use of combined compared to single agent analgesia is safe, significantly reduced pain and improved patient satisfaction after a caesarian section (CS).


Sarcomere mechanics in striated muscles: from molecules to sarcomeres to cells.
Muscle contraction is commonly associated with the cross-bridge and sliding filament theories, which have received strong support from experiments conducted over the years in different laboratories. However, there are studies that cannot be readily explained by the theories, showing 1) a plateau of the force-length relation extended beyond optimal filament overlap, and forces produced at long sarcomere lengths that are higher than those predicted by the sliding filament theory; 2) passive forces at long sarcomere lengths that can be modulated by activation and Ca2+, which changes the force-length relation; and 3) an unexplained high force produced during and after stretch of activated muscle fibers. Some of these studies even propose "new theories of contraction." While some of these observations deserve evaluation, many of these studies present data that lack a rigorous control and experiments that cannot be repeated in other laboratories. This article reviews these issues, looking into studies that have used intact and permeabilized fibers, myofibrils, isolated sarcomeres, and half-sarcomeres. A common mechanism associated with sarcomere and half-sarcomere length nonuniformities and a Ca2+-induced increase in the stiffness of titin is proposed to explain observations that derive from these studies.


Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL).
The ability of T cells that accompany or develop from transplanted allogeneic marrow to eradicate leukemia has been repeatedly demonstrated in animal models. Whether a similar graft-versus-leukemia effect exists in humans who have received transplants for acute lymphoblastic leukemia can be addressed by five different clinical observations: comparisons of autologous versus allogeneic transplantation, comparisons of syngeneic versus allogeneic transplantation, examination of relapse rates in allogeneic recipients who do or do not develop GVHD, the impact of T-cell depletion on relapse rates, and the results of donor lymphocyte infusions to treat posttransplant relapse. The bulk of available evidence supports the view that a potent GVL effect exists in patients treated for ALL. These results provide a strong rationale for efforts to develop techniques to further capitalize on the GVL effect.


Minimax current density gradient coils: analysis of coil performance and heating.
Standard gradient coils are designed by minimizing the inductance or resistance for an acceptable level of gradient field nonlinearity. Recently, a new method was proposed to minimize the maximum value of the current density in a coil additionally. The stated aim of that method was to increase the minimum wire spacing and to reduce the peak temperature in a coil for fixed efficiency. These claims are tested in this study with experimental measurements of magnetic field and temperature as well as simulations of the performance of many coils. Experimental results show a 90% increase in minimum wire spacing and 40% reduction in peak temperature for equal coil efficiency and field linearity. Simulations of many more coils indicate increase in minimum wire spacing of between 50 and 340% for the coils studied here. This method is shown to be able to increase coil efficiency when constrained by minimum wire spacing rather than switching times or total power dissipation. This increase in efficiency could be used to increase gradient strength, duty cycle, or buildability.


Effect of posterior instrumented fusion on three-dimensional volumetric growth of cervical ossification of the posterior longitudinal ligament: a multiple regression analysis.
Despite the fact that ossification of posterior longitudinal ligament (OPLL) is a three-dimensional disease, conventional studies have focused mainly on a two-dimensional measurement, and it is difficult to accurately determine the volume of OPLL growth and analyze the factors affecting OPLL growth after posterior decompression (laminoplasty or laminectomy and fusion). The present study aimed to investigate the factors affecting OPLL volume growth using a three-dimensional measurement. This was a retrospective case study. Eighty-three patients with cervical OPLL who were diagnosed as having multilevel cervical OPLL of more than three levels on cervical computed tomography (CT) scans were retrospectively reviewed from June 1, 1998, to December 31, 2015. The OPLL volume from the C1 vertebrae to the C7 vertebrae was measured on preoperative and the most recent follow-up CT scans. Eighty-three patients were retrospectively examined for age, gender, body mass index, hypertension, diabetes, type of OPLL, surgical method, preoperative cervical curvature, and preoperative and postoperative cervical range of motion. Preoperative cervical CT and the most recent follow-up cervical CT scans were converted to Digital Imaging and Communications in Medicine data, and the OPLL volume was three-dimensionally measured using the Mimics program (Materialise, Leuven, Belgium). The OPLL volume growth was analyzed using univariate and multivariate analyses. The average follow-up period was 32.36 (±23.39) months. Patients' mean age was 54.92 (±8.21) years. In univariate analysis, younger age (p=.037) and laminoplasty (p=.012) were significantly associated with a higher mean annual growth rate of OPLL (%/y). In multivariate analysis, only laminoplasty (p=.027) was significantly associated with a higher mean annual growth rate of OPLL (%/y). The mean annual growth rate of OPLL was about seven times faster with laminoplasty (8.00±13.06%/y) than with laminectomy and fusion (1.16±9.23%/y). Posterior instrumented fusion has the effect of reducing OPLL growth rate compared with motion-preserving laminoplasty. Patients' age and the surgical method need to be considered in surgically managing the multilevel OPLL.


Clinical and Financial Outcomes Evaluation of Multimodal Pharmacist Warfarin Management of a Statewide Urban and Rural Population.
To evaluate the efficacy, safety, and indirect financial outcomes of pharmacist face-to-face warfarin management with telephone-based distance management utilizing local laboratories or patient self-testing (PST). A retrospective analysis of a clinic population of 336 patients on established warfarin therapy distributed statewide in rural and urban settings over a 6-month period was conducted. Participants were stratified into face-to-face management, telephone-based management utilizing local laboratory testing, and telephone-based management utilizing PST. The primary outcome of international normalized ratio (INR) time in therapeutic range (TTR) for face-to-face management was significantly greater than distance management utilizing local laboratory testing (69.0% vs 60.5%, P = .0032). No difference was observed between face-to-face management and PST (69.0% vs 68.0%, P = .25). No significant difference in bleeding or thromboses was observed. Although increased clinician time was utilized during face-to-face encounters compared to telephone encounters (8.7-minute face-to-face, 5.5-minute local laboratory, and 5.4-minute PST), face-to-face encounters tended to be billable at lower levels, whereas telephone-based encounters were billable at higher levels. A multimodal approach to pharmacist warfarin management of a patient population distributed statewide in rural and urban locations is effective despite TTR differences associated with INR testing used in distance management. PST may improve warfarin treatment outcomes and adherence in distance management, particularly when the use of alternative oral anticoagulants is inappropriate. Although time and billing differences between face-to-face and distance management exist, clinical and safety outcomes remain acceptable despite encounter complexity and support reimbursement of pharmacist anticoagulation management in all settings.


Refractive errors in Singapore and Xiamen, China--a comparative study in school children aged 6 to 7 years.
To compare and contrast the prevalence of myopia and other refractive errors in Xiamen city, Xiamen countryside (Southern China), and Singapore. One hundred thirty-two schoolchildren aged 6 to 7 years from Xiamen city, 104 from Xiamen countryside, and 146 from Singapore city were recruited to join the study. Cycloplegic autorefraction, keratometry, and biometry measurements were performed on all children. The prevalence of myopia was 12.3% in Singapore city, 9.1% in Xiamen city, and 3.9% in Xiamen countryside. The prevalence of astigmatism was higher in Singapore compared with Xiamen. The rates of hyperopia and anisometropia were similar in all three locations. The myopia rate in Singapore city was higher than in Xiamen city; the lowest rates were found in Xiamen countryside. As the Chinese population from all three sites is of similar genetic stock (predominantly from Southern China), it is postulated that the differences in myopia rates in these three localities may be related to environmental factors.


An evaluation of enforced rapid proteasomal degradation as a means of enhancing vaccine-induced CTL responses.
The HIV-1 Gag protein is an attractive target for CTL-based vaccine strategies because it shows less sequence variability than other HIV-1 proteins. In an attempt to increase the immunogenicity of HIV-1 Gag, we created Gag variants that were targeted to the proteasomal pathway for rapid degradation. This enhanced rate of degradation was associated with increased presentation of MHC class I-associated antigenic peptides on the cell surface. Despite this, immunizing mice with either plasmid DNA or recombinant vaccinia vectors expressing unstable Gag failed to produce significant increases in bulk CTL responses or Ag-specific production of IFN-gamma by CD8(+) T cells compared with mice immunized with stable forms of Gag. Production of IFN-gamma by CD4(+) T cells was also impaired, and we speculate that the abrogation of CD4(+) T cell help was responsible for the impaired CTL response. These results suggest that vaccine strategies designed to increase the density of peptide-MHC class I complexes on the surfaces of APC may not necessarily enhance immunogenicity with respect to CTL responses.


Metastasis from lung carcinoma to the finger: A case report.
Skeletal metastasis in the hand is exceedingly rare. In approximately 10% of the reported cases, it occurs as the primary manifestation of an occult malignancy. The early, correct diagnosis is warranted given the patient's poor prognosis. Conventional radiographs and MRI are helpful in diagnosis, but histology is needed for confirmation. Due to the usual wide spread malignancy, palliation is the primary goal of treatment. Disarticulation and resection of the affected ray is the most common approach. We present a case of a skeletal metastasis from a lung carcinoma in the fourth digit of the hand and performed a curettage of the metastatic tumor, followed by a stabilization of the middle phalanx with a bone cement spacer and postoperative local radiation. The postoperative pain relief was acceptable and the functional outcome was relatively good, and therefore indicates that this treatment option could be considered in the palliative care setting of acrometastatis.


Recent Advances in the Chemistry and Therapeutic Evaluation of Naturally Occurring and Synthetic Withanolides.
Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.


The influence of primary caregivers on the sexual behavior of early adolescents.
To describe rates of sexual intercourse initiation, anticipated level of sexual activity in the next 12 months, and other risk behaviors among fifth graders and to examine parental factors associated with such behaviors. This study is based on a cross-sectional, self-administered survey conducted with a nonrandom sample of 408 fifth graders and their caregivers. Children answered questions regarding sexual intercourse initiation, anticipated sexual activity in the next 12 months, and involvement in other risk behaviors. Caregivers answered questions about parenting factors such as monitoring behaviors, parent-child relationship quality, and parent-child communication. Bivariate and multivariable analyses examined the association of these variables with the adolescents' behaviors. Almost 5% of girls and 17% of boys reported they had engaged in sexual intercourse. Only 34% of girls and 13% of boys said they did not expect to engage in any type of sexual contact in the next 12 months if they were going with someone they "liked a lot." Parental factors associated with fewer risk behaviors and expected sexual behaviors included higher levels of monitoring, fewer communication barriers, less permissive attitudes regarding adolescent sexual behavior, higher relationship quality with child, having fewer than five children in the household, higher levels of education, and being employed. Significant gender interactions were found for several variables. Adolescents are initiating sexual intercourse at extremely young ages. To delay early sexual activity and prevent adolescent pregnancy, prevention efforts must begin during the elementary school years and include those who raise and care for the adolescent.


Cell-specific differences in the processing of the R14W CAIV mutant associated with retinitis pigmentosa 17.
Retinitis pigmentosa is a highly heterogeneous form of inherited blindness which affects more than 1.3 million individuals worldwide. The RP17 form of the disease is caused by an arginine to tryptophan (R14W) mutation in the signal sequence of carbonic anhydrase IV (CAIV). While CAIV is expressed in the choriocapillaries of the eye and renal epithelium, the R14W mutation results in an exclusively ocular phenotype in affected individuals. In order to investigate the mechanism of disease in RP17 and the lack of kidney phenotype, we compared the subcellular localization and post-translational processing of wild-type (WT)- and mutant-CAIV in three cell types. We show using immunocytochemistry that unlike WT CAIV which is transported to the plasma membrane of transfected COS-7 and HT-1080 cells, the R14W mutant CAIV is retained in the endoplasmic reticulum. Western blot analyses further reveal that whereas the WT CAIV is processed to its mature form in both these cell lines, significant levels of the R14W mutant protein remain in its immature form. Importantly, flow cytometry experiments demonstrate that compared to WT CAIV protein, expression of specifically the R14W CAIV results in an S and G2/M cell-cycle block, followed by apoptosis. Interestingly, when the above experiments were repeated in the human embryonic kidney cell line, HEK-293, strikingly different results were obtained. These cells were unaffected by the expression of the R14W mutant CAIV and were able to process the mutant and WT protein equally effectively. This study has important implications for our understanding of the RP17 phenotype.


Leaching of lead from computer printed wire boards and cathode ray tubes by municipal solid waste landfill leachates.
The proper management of discarded electronic devices (E-waste) is an important issue for solid waste professionals because of the magnitude of the waste stream and because these devices often contain a variety of toxic metals (e.g., lead). While recycling of E-waste is developing, much of this waste stream is disposed in landfills. Leaching tests are frequently used to characterize the potential of a solid waste to leach when disposed in a landfill. In the United States, the Toxicity Characteristic Leaching Procedure (TCLP) is used to determine whether a solid waste is a hazardous waste by the toxicity characteristic. The TCLP is designed to simulate worse-case leaching in a landfill environment where the waste is co-disposed with municipal solid waste (MSW). While the TCLP is a required analysis from a regulatory perspective, the leachate concentrations measured may not accurately reflect the concentrations observed under typical landfill conditions. Another method that can be performed to assess the degree a pollutant might leach from a waste in a landfill is to use actual landfill leachate as the leaching solution. In this study, two lead-containing components found in electronic devices (printed wire boards from computers and cathode ray tubes from computers and televisions) were leached using the TCLP and leachates from 11 Florida landfills. California's Waste Extraction Test (WET) and the Synthetic Precipitation Leaching Procedure were also performed. The results indicated that the extractions using MSW landfill leachates resulted in lower lead concentrations than those by the TCLP. The pH of the leaching solution and the ability of the organic acids in the TCLP and WET to complex with the lead are factors that regulate the amount of lead leached.


Effect of antiretroviral therapy on asymptomatic malaria parasitaemia in HIV-1 infected children.
To investigate the effect of antiretroviral (ARV) therapy on the level of asymptomatic malaria parasitaemia in HIV-1 infected children. Sixty-six HIV infected children had blood films prepared for malaria parasite identification and count. Mean parasite densities were compared across clinical stages and immunologic categories of disease and antiretroviral treatment status. Forty-five (68%) were less than 6 years old and 50 (75.7%) had advanced HIV disease. Twenty seven (41%) were on antiretroviral therapy. The prevalence of ASMP in the treated and untreated group was 44.4% and 15.4% respectively (p<0.01). The mean parasite density in the ARV treatment group was also significantly higher than in the untreated group (p=0.0071). ARV therapy seems to be associated with higher rates of ASMP and higher mean parasite counts.


Human-like telomeres in Zostera marina reveal a mode of transition from the plant to the human telomeric sequences.
A previous study describing the genome of Zostera marina, the most widespread seagrass in the Northern hemisphere, revealed some genomic signatures of adaptation to the aquatic environment such as the loss of stomatal genes, while other functions such as an algal-like cell wall composition were acquired. Beyond these, the genome structure and organization were comparable with those of the majority of plant genomes sequenced, except for one striking feature that went unnoticed at that time: the presence of human-like instead of the expected plant-type telomeric sequences. By using different experimental approaches including fluorescence in situ hybridization (FISH), genome skimming by next-generation sequencing (NGS), and analysis of non-coding transcriptome, we have confirmed its telomeric location in the chromosomes of Z. marina. We have also identified its telomerase RNA (TR) subunit, confirming the presence of the human-type telomeric sequence in the template region. Remarkably, this region was found to be very variable even in clades with a highly conserved telomeric sequence across their species. Based on this observation, we propose that alternative annealing preferences in the template borders can explain the transition between the plant and human telomeric sequences. The further identification of paralogues of TR in several plant genomes led us to the hypothesis that plants may retain an increased ability to change their telomeric sequence. We discuss the implications of this occurrence in the evolution of telomeres while introducing a mechanistic model for the transition from the plant to the human telomeric sequences.


Effects of Circumpapillary Retinal Nerve Fiber Layer Segmentation Error Correction on Glaucoma Diagnosis in Myopic Eyes.
In a myopic population, we investigated the occurrence of circumpapillary retinal nerve fiber layer (RNFL) segmentation errors that required manual correction in optical coherence tomography (OCT) and its effect on glaucoma diagnostic capability of OCT. Myopic subjects (spherical equivalent refractive error <-3 D) with and without primary open-angle glaucoma were recruited. Three circumpapillary RNFL scans with diameters of 3.45, 4.50, and 6.00 mm were obtained using spectral-domain OCT. RNFL segmentation errors were manually corrected. Receiver operating characteristic curves of retinal nerve fiber layer thickness (RNFLT) were obtained and area under the curves were calculated before and after manual correction. In total, 90 myopic eyes with glaucoma (90 patients; visual field mean deviation, -9.5±7.1 dB) and 58 myopic eyes without glaucoma (58 control subjects) were included. Glaucomatous eyes required manual correction more frequently than control eyes (56% vs. 32% of RNFL OCT scans; P<0.001). After manual correction in the glaucoma group, the global RNFLT decreased significantly from 61.8 to 57.5 µm (P=0.025), 50.8 to 47.2 µm (P=0.019), and 45.5 to 39.6 µm (P=0.006) for the 3.45-, 4.50-, and 6.00-mm scans, respectively. After manual correction of RNFL segmentation errors, the glaucoma diagnostic capability of the global RNFLT improved significantly; the area under the curves increased from 0.827 to 0.886 (P=0.017), 0.829 to 0.880 (P=0.033), and 0.762 to 0.846 (P=0.006) for the 3.45-, 4.50-, and 6.00-mm scans, respectively. A significant proportion of myopic eyes had RNFL segmentation errors in automated spectral-domain OCT analysis, decreasing glaucoma diagnostic capability of OCT RNFLT measurement.


Analysis of retinal arteriolar structure in never-treated patients with essential hypertension.
Increased wall-to-lumen ratio of small arteries is a predictor of adverse cardiovascular prognosis. We aimed to analyze retinal arteriolar structure in never-treated patients with essential hypertension and to test whether elevated blood pressure is associated with an increased wall-to-lumen ratio of retinal arterioles. The study cohort comprised 21 untreated male patients with essential hypertension (mean age 39.1 +/- 5.4 years) and 29 untreated normotensive men (mean age 36.7 +/- 5.9 years). Wall-to-lumen ratio of retinal arterioles was assessed in vivo using scanning laser Doppler flowmetry. Patients with essential hypertension had a higher wall-to-lumen ratio of retinal arterioles than normotensive individuals (0.36 +/- 0.1 vs. 0.28 +/- 0.1, P = 0.028). Wall cross-sectional area of retinal arterioles did not differ between the study groups. The growth index, indicating the percentage of difference in average wall cross-sectional area of retinal arterioles between both groups, was 18%. Both systolic (r = 0.360, P = 0.010) and diastolic (r = 0.536, P < 0.001) blood pressures were related to wall-to-lumen ratio of retinal arterioles. Multiple regression analysis including a variety of known cardiovascular risk factors revealed that blood pressure is independently associated with an increased wall-to-lumen ratio of retinal arterioles (systolic blood pressure: beta = 0.417, P = 0.012; diastolic blood pressure: beta = 0.548, P = 0.001). The changes in arteriolar structure of retinal vessels in our study cohort revealed a similar pattern to that observed previously by other investigators in subcutaneous small arteries in essential hypertension. Blood pressure emerged as an important and independent determinant of wall-to-lumen ratio of retinal arterioles.


Effect of Electromagnetic Field Exposure on Mouse Brain Morphological and Histopathological Profiling.
Mobile phones (MP) and other electronic and communication devices that are used daily expose users to electromagnetic fields (EMF) and contribute to an increasing incidence of neurological disorders. Brain tissue is the closest organ to the MP as it operates, thus the influence of MP radiation on brain tissue is of particular concern, although research is still inconclusive. The present study investigated the possible effect of an EMF (1,350-1,375 megahertz (MHz)) from an MP on morphological and histopathological profiles in the mouse brain. Healthy BALB/c mice were assigned to three equal groups (a control and two experimental groups, n = 10 each). Experimental mice were exposed to EMFs continuously for 72 h, those of experimental group I to a 1,350 MHz field at a specific absorption rate (SAR) of 4.0 W/kg, and group II to a 1,375 MHz field EMF at an SAR of 4.0 W/kg. Brain segmentation and histopathological analysis were applied to detect changes in the morphometric parameters of the brain lobes and identify pathological lesions, respectively. Histopathology results revealed shrinkage of pyramidal neurons, presence of mild perivascular and perineural oedema, and some vacuolation of neurons and glial cells derived from mouse great hemispheres. The lesions also included reduction of Purkinje cells, vacuolisation of neurons and glial cells, and interstitial oedema in the cerebellum. MP distance of 3 cm from the cage may induce appreciable morphological changes in mouse brain structures; therefore, more comprehensive research is essential for assessment of safe distance. These pronounced effects may interfere with the results of laboratory tests on murine experimental models in veterinary or biomedical research.


Elimination by Gamma Irradiation of Salmonella spp. and Strains of Staphylococcus aureus Inoculated in Bison, Ostrich, Alligator, and Caiman Meat †.
There is an expanding industry for the marketing of high-value meats from animals other than the typical domesticated species, including, but not limited to, bison, ostrich, alligator, and caiman. In this study we compared the gamma radiation resistance of a mixture of salmonellae ( Salmonella dublin , S. enteritidis , S. newport , S. senftenberg , and S. typhimurium ) and a mixture of Staphylococcus aureus strains (ATCC 13565, ATCC 25923, and B124) when present on ground bison, ostrich, alligator, and caiman meats at 5°C. A minimum of five doses were used to establish the D values, and the studies were replicated three times. Because the type of meat did not significantly (P < 0.05) alter the radiation resistance of salmonellae and of S. aureus only slightly in the case of ostrich meat, all of the results for each organism were combined to obtain radiation D values of 0.53 ± 0.02 and 0.37 ± 0.01 kGy for Salmonella spp. and S. aureus , respectively. The authors conclude that both of these food-borne pathogens, if present, can be eliminated or greatly reduced in number, depending upon the level of contamination, from these meats by gamma radiation doses between 1.5 and 3.0 kGy at 5°C, the doses currently approved by the FDA and USDA for the irradiation of poultry. The authors also conclude that similar, if not identical, control of food-borne pathogens should be expected on edible meats in general, not just on those that are generically related.


The cost-effectiveness of misoprostol in preventing serious gastrointestinal events associated with the use of nonsteroidal antiinflammatory drugs.
To reexamine the cost-effectiveness of misoprostol, using data from a recently published placebo-controlled trial of misoprostol in > 8,000 patients with rheumatoid arthritis (RA) taking nonsteroidal antiinflammatory drugs (the Misoprostol Ulcer Complications Outcome Safety Assessment [MUCOSA] study). Actual clinical events and the rates of endoscopies and upper gastrointestinal (GI) radiographic series, hospitalizations, and surgery for these events were derived from the MUCOSA study and used in a decision analysis. Estimates of costs for the management of these events were derived from the Ontario Case Cost Project database and published economic evaluations; costs were adjusted to 1994 Canadian dollars. Incremental cost-effectiveness (from the viewpoint of the provincial health care plan in Canada) was calculated for the original trial population (risk of a serious GI complication 1%) and for the subsets of patients with medium (3%) and high (6%) risk. For the original study population, averting 1 serious GI complication by prescribing misoprostol would cost an additional $94,766 (Canadian; range $60,286-137,146). For patients with previous peptic ulcer disease (medium risk), the cost would be $14,943 (range $10,912-32,157), and for patients with previous peptic ulcer disease and age > 75 (high risk), the cost would be $4,101 (range $-220 to $18,146). Prescribing misoprostol for all patients with RA who are > or =52 years old costs $94,766 for each additional GI event averted. However, when patients at higher risk are specifically selected, the cost per averted GI complication is markedly reduced. These results, based on actual serious event rates and actual data on endoscopies and upper GI series, hospitalizations, and surgeries, provide a better estimate of the true cost-effectiveness of misoprostol than previous analyses based on endoscopic data and modeling of all resource utilizations.


Spreading Depolarizations Contribute to the Acute Behavior Deficits Associated With a Mild Traumatic Brain Injury in Mice.
Concussions or mild traumatic brain injuries (mTBIs) are often described and diagnosed by the acute signs and symptoms of neurological dysfunction including weakness, dizziness, disorientation, headaches, and altered mental state. The cellular and physiological mechanisms of neurological dysfunction and acute symptoms are unclear. Spreading depolarizations (SDs) occur after severe TBIs and have recently been identified in closed-skull mouse models of mTBIs. SDs are massive waves of complete depolarization that result in suppression of cortical activity for multiple minutes. Despite the clear disruption of brain physiology after SDs, the role of SDs in the acute neurological dysfunction and acute behavioral deficits following mTBIs remains unclear. We used a closed-skull mouse model of mTBI and a series of behavioral tasks collectively scored as the neurological severity score (NSS) to assess acute behavior. Our results indicate that mTBIs are associated with significant behavioral deficits in the open field and NSS tasks relative to sham-condition animals. The behavioral deficits associated with the mTBI recovered within 3 h. We show here that the presence of mTBI-induced bilateral SDs were significantly associated with the acute behavioral deficits. To identify the role of SDs in the acute behavioral deficits, we used exogenous potassium and optogenetic approaches to induce SDs in the absence of the mTBI. Bilateral SDs alone were associated with similar behavioral deficits in the open field and NSS tasks. Collectively, these studies demonstrate that bilateral SDs are linked to the acute behavioral deficits associated with mTBIs.


PIK3CA and p53 Mutations Promote 4NQO-Initated Head and Neck Tumor Progression and Metastasis in Mice.
The PI3K signaling pathway is frequently mutated in head and neck squamous cell carcinoma (HNSCC), often via gain-of-function (GOF) mutations in the PIK3CA gene. Here, we present novel genetically engineered mouse models (GEMM) carrying a GOF allele Loxp-STOP-Loxp(LSL)-PIK3CAH1047R (E20) alone or in combination with heterozygous LSL-p53+/R172H (p53) mutation with tissue-specific expression to interrogate the role of oncogenic PIK3CA in transformation of upper aerodigestive track epithelium. We demonstrated that the GOF PIK3CA mutation promoted progression of 4-nitroquinoline 1-oxide-induced oral squamous cell carcinoma (OSCC) in both E20 single mutant and E20/p53 double mutant mice, with frequent distal metastasis detected only in E20/p53 GEMM. Similar to in human OSCC, loss of p16 was associated with progression of OSCC in these mice. RNA-seq analyses revealed that among the common genes differentially expressed in primary OSCC cell lines derived from E20, p53, and E20/p53 GEMMs compared with those from the wild-type mice, genes associated with proliferation and cell cycle were predominantly represented, which is consistent with the progressive loss of p16 detected in these GEMMs. Importantly, all of these OSCC primary cell lines exhibited enhanced sensitivity to BYL719 and cisplatin combination treatment in comparison with cisplatin alone in vitro and in vivo, regardless of p53 and/or p16 status. Given the prevalence of mutations in p53 and the PI3K pathways in HNSCC in conjunction with loss of p16 genetically or epigenetically, this universal increased sensitivity to cisplatin and BYL719 combination therapy in cancer cells with PIK3CA mutation represents an opportunity to a subset of patients with HNSCC. IMPLICATIONS: Our results suggest that combination therapy of cisplatin and PI3K inhibitor may be worthy of consideration in patients with HNSCC with PIK3CA mutation.


A Diet Enriched with Red Sorghum Flaked Biscuits, Compared to a Diet Containing White Wheat Flaked Biscuits, Does Not Enhance the Effectiveness of an Energy-Restricted Meal Plan in Overweight and Mildly Obese Adults.
Whole grain sorghum is a promising ingredient in foods, especially those targeting satiety and weight control. This study aimed to test weight loss effects of a whole grain red sorghum product incorporated into an energy-restricted diet. Sixty subjects (46 females) were randomized to either a sorghum (intervention) or white wheat (control) group, receiving 45 g of flaked cereal biscuits to include daily in their prescribed diets for 12 weeks. Primary outcome was weight loss. Secondary outcomes included plasma glucose, glycosylated hemoglobin (HbA1c), insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triacylglycerides (TAG), interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), and total antioxidant capacity (TAC; measured at 0 and 12 weeks). After 12 weeks, there were no significant differences in weight loss or any clinical variables between a wheat control and sorghum cereal group in an energy-restricted diet. Equivalent amounts of weight were lost (p = 0.369) in both groups, and the majority of clinical indices such as fasting glucose, insulin, cholesterol, and key inflammatory biomarkers showed significant beneficial changes over time (p < 0.05). Although both groups experienced significant weight loss and general improvement in a number of clinical measures, no effects appeared specifically related to sorghum consumption. Further clinical trials are necessary to establish an evidence base for weight loss effects from chronic sorghum intake. Sorghum represents a viable, gluten-free grain alternative in the formulation of novel food products.


Validation of a latent construct for dementia case-finding in Mexican-Americans.
We have constructed a latent dementia proxy, "δ", and validated it in several datasets, including well characterized subjects participating in the Texas Alzheimer's Research and Care Consortium (TARCC) study. It may be possible to construct δ homologs from almost any ad hoc combination of cognitive and functional status measures. δ homologs may also be relatively immune to measurement error, including cultural, linguistic, or educational biases. These properties make factor scores derived from latent variables a potentially attractive solution for dementia case-finding in rural or minority populations. Here we have explored an alternative and briefer assessment by which to construct a δ homolog and validate the resulting latent variable (dMA) in Mexican-American (MA) TARCC subjects. dMA, composed of simple "bedside" dementia screening instruments, achieves Areas Under the Receiver Operative Curve that rival those of δ itself. Ethnicity has a small effect on dMA's performance. These results suggest that it may be possible to validly export dMA into other MA populations, or to export δ homolog factor scores from one population to another.


"Casing" the research case study.
The wide variation in definitions of the research case study can make it difficult for health sciences researchers to see all of the possibilities for this form of inquiry. Case studies are defined here as singular combinations of diverse arrays of methodological approaches directed toward maintaining "empirical intimacy" with the one or more temporally and spatially defined objects researchers construct and target for study. The cases selected for study are made as opposed to found through an iterative and theory-laden process called "casing." Case- as opposed to variable-oriented analysis helps researchers maintain "empirical intimacy" with the cases in their case studies. Case studies may be useful in enhancing programs of research in instrument and intervention development.


Pre-development denudation rates for the Great Barrier Reef catchments derived using 10Be.
Understanding of the pre-development, baseline denudation rates that deliver sediment to the Great Barrier Reef (GBR) has been elusive. Cosmogenic 10Be in sediment is a useful integrator of denudation rates and sediment yields averaged over large spatial and temporal scales. This study presents 10Be data from 71 sites across 11 catchments draining to the GBR: representing 80% of the GBR catchment area and provide background sediment yields for the region. Modern, short-term, sediment yields derived from suspended load concentrations are compared to the 10Be data to calculate an Accelerated Erosion Factor (AEF) that highlights denudation "hot-spots" where sediment yields have increased over the long-term background values. The AEF results show that 58% basins have higher modern sediment yields than long-term yields. The AEF is considered a useful approach to help prioritise on-ground investments in remediation and the additional measured empirical data in this paper will help support future predictive models.


Cancer incidence among workers in six Norwegian aluminum plants.
This study investigated associations between exposure to polycyclic aromatic hydrocarbons (PAH) and the incidence of lung, bladder, kidney, and pancreatic cancer among Norwegian aluminum plant workers. Cancer incidence was investigated from 1953 to 1996 among 11,103 men employed for more than 3 years in the industry, giving 272,554 person-years during follow-up. A job exposure matrix was constructed to estimate exposure to particulate PAH and fluorides. The observed cases of cancer were compared with expected figures calculated from national rates. Dose-response relations were investigated by internal comparisons using Poisson regression and stratified analyses for standardized incidence ratio. Potential confounding by smoking was investigated in subanalyses restricted to 3 of the plants. The study showed an overall excess for bladder cancer, standardized incidence ratio 1.3 (95% confidence interval 1.1-1.5), which increased with increasing cumulative exposure to PAH and reached a relative risk of about 2 for the upper exposure category in the analysis with 30 years of lag time. There was no association between cumulative PAH exposure and lung cancer, but there were indications of an elevated risk of kidney cancer among the most heavily PAH-exposed persons in the analyses with a lag time of 30 years. For pancreatic cancer we found a higher incidence among the PAH-exposed persons than among the unexposed ones, but no clear dose-response association was found. The study showed an association between bladder cancer and exposure to PAH, but gave no support to an association between PAH exposure and lung cancer in the primary aluminum industry.


[What characterizes the problem psychiatric patient? Results of a study of patient descriptions using the Psychiatric Personnel Order].
In recent years, economic pressure on extended and repeated psychiatric hospitalisation have increased dramatically. At the same time, diagnostic approaches, e.g., the new concept of the "young adult chronic patient" have improved. The first part of this article summarises reports and experiences on the chronic mentally ill and the so-called "heavy users" of psychiatric hospitalisation. Although the number of studies evaluating this group is small, several characteristics can be identified. Subsequently, a study is presented that deals with psychiatric problem patients in a special way, namely the A2-categorisation according to the German Psychiatric Personnel Regulation (Psychiatrie-Personalverordnung [Psych-PV]). The study is based on 170 consecutive admissions to the Department of General Psychiatry of a large German state hospital, who are characterised as normal (A1) and intensive patients (A2), respectively. The study aimed at describing difficult-to-treat patients or those whose treatment demands large human resources. Medical histories, sociodemographic and psychopathological data as well as subjective health status data of these patients were analysed by standardised and validated instruments (e.g., BPRS, CGI, SF-36, GAF). Results show that the patients under study suffered mainly from schizophrenic psychosis according to ICD-9. Patients categorised into A2 showed a high degree of psychopathology and little insight into their disease. Further it can be demonstrated that they used more therapeutic help from general practitioners rather than from specialists in psychiatry prior to admission. In conclusion, it is suggested to evaluate concepts, e.g., new treatment methods in respect of motivating schizophrenic patients, new typological methods to better diagnosis and to treat psychiatric problem patients via new treatment modalities such as Case Management or inpatient settings for double diagnoses.


Autologous fat grafting for whole breast reconstruction.
This is the first reported case of a patient who had a single-stage large-volume breast reconstruction with autologous fat grafting, following rotation flap approach (RoFA) mastectomy. The purpose of this case study was to evaluate the viability of reconstruction of the breast by autologous fat grafting alone, in the context of RoFA mastectomy. The hypothesis was that there would be minimal interval loss of autologous fat on the whole breast reconstruction side. Right RoFA mastectomy was used for resection of an invasive primary breast cancer and resulted in the right breast skin envelope. Eleven months later, the patient underwent grafting of 400 ml of autologous fat into the skin envelope and underlying pectoralis major muscle. Outcome was assessed by using a validated 3D laser scan technique for quantitative breast volume measurement. Other outcome measures included the BREAST-Q questionnaire and 2D clinical photography. At 12-month follow-up, the patient was observed to have maintenance of volume of the reconstructed breast. Her BREAST-Q scores were markedly improved compared with before fat grafting, and there was observable improvement in shape, contour, and symmetry on 2D clinical photography. The 2 new techniques, RoFA mastectomy and large-volume single-stage autologous fat grafting, were used in combination to achieve a satisfactory postmastectomy breast reconstruction. Novel tools for measurement of outcome were the 3D whole-body laser scanner and BREAST-Q questionnaire. This case demonstrates the potential for the use of fat grafting for reconstruction. Outcomes in a larger patient populations are needed to confirm these findings.


Young adult males' motivators and perceived barriers towards eating healthily and being active: a qualitative study.
There is a lack of understanding of young men's perspectives in obesity-related research. This study aims to: (1) identify young men's perceived motivators and barriers in adopting healthy eating and physical activity behaviours, and (2) explore any differences in responses by weight status categories. Ten focus groups (32-63 minutes; 3-9 participants per group) were conducted with 61 young men (BMI: 25.3 ± 5.1 kg/m(2), aged: 18-25 years) from the Hunter region, New South Wales, Australia. There were 35 (57.4 %) healthy weight men and 26 (42.6 %) overweight/ obese men. Three groups were with healthy weight participants, three with overweight/obese participants and four with mixed-BMI participants. Sessions were audio-recorded and transcribed. Data analysis was conducted by an independent researcher using NVIVO10. Motivators for healthy eating grouped into four themes: physical health (e.g. to live longer), sport or performance (e.g. to support their sporting goals), physical appearance (e.g. sexual attractiveness) and social influences (e.g. societal expectations to eat healthy), while key motivators for physical activity were: physical appearance (e.g. sexual attractiveness), social inclusion (e.g. making friends), physical and mental health (e.g. relieve stress) and improvements for sport or performance (e.g. improve fitness). Themes for key barriers to eating healthy were: intrinsic (e.g. perceived effort to adopt healthy eating), logistic (e.g. cost), and social factors (e.g. peer influence), while busy lifestyles (e.g. lack of time), logistic (e.g. cost), cognitive-emotional (e.g. feelings of inferiority) and social factors (e.g. family upbringing) were key barriers for physical activity. Responses varied little by BMI status. This research emphasises the importance of consulting young men when developing healthy lifestyle programs that aim to promote healthy eating and physical activity in young men. Future research is needed to identify the most effective ways to address their motivators and barriers in intervention research.


Endoaneurysmorrhaphy for left ventricular aneurysm. Follow-up in 69 patients.
We reviewed the cases of 69 consecutive patients who underwent physiologic reconstruction of the left ventricular cavity with an endoventricular patch (endoaneurysmorrhaphy) after aneurysmectomy. Eight patients had isolated endoaneurysmorrhaphy, 60 patients had concomitant coronary artery bypass grafting, and 1 patient had concomitant closure of an atrial septal defect. The primary indications for operation were angina pectoris (New York Heart Association functional class I or II) in 42 patients and dyspnea (functional class III or IV) in 27 patients. The preoperative left ventricular ejection fraction evaluated with ventriculography was 28.95% +/- 7.27% (mean +/- standard error of the mean). The global perioperative mortality rate was 2.8%. Total follow-up was 139.3 patient-years. The late mortality rate was 4.3% per patient-year. A marked increase was found in the mean postoperative left ventricular ejection fraction of the patients: 41.91% +/- 11.83%. Survivors were interviewed in person: their functional status was class I or II in 58 patients and class III in 3 patients. We conclude that left ventricular endoaneurysmorrhaphy results in satisfactory functional improvement and can be performed with relatively low early and late mortality rates.


Effect of prey richness on a consumer's intrinsic growth rate.
The intrinsic growth rate of non-selective microbivores increases asymptotically with increasing prey biomass, but we do not know how intrinsic growth rate is affected by prey richness. The objective of this experiment was to determine the effect of prey richness on the growth kinetics of nematode predators while grazing on mixed bacterial lawns. We found that the intrinsic growth rate of Caenorhabditis elegans in laboratory culture increased asymptotically with prey richness. The mechanism of this pattern was primarily due to the best available prey species in the mixture: the intrinsic growth rate of the consumer feeding on a mixture of prey was approximately equal to the intrinsic growth rate of the predator when feeding on the single best prey in monoculture. This was analogous to the selection effect observed in biodiversity-ecosystem functioning relationships. Generation time, and not reproductive output, was the life history trait component that was most consistent with the pattern of intrinsic growth rate. Our results suggest that in order to link invertebrate consumers' growth rates to their microbial species composition in the field, it will be necessary to determine the ability of microbivorous invertebrates to selectively forage in natural environments and to better understand the micro-scale distribution of microbial communities in their natural environments.


Tumor cells with organ-specific metastatic ability show distinctive trafficking in vivo: analyses by positron emission tomography and bioimaging.
To elucidate the behavior of various metastatic tumor cells with different characteristics in the blood flow, we have developed a system to investigate real-time trafficking using positron emission tomography. In this study, positron-labeled cells, i.e., lung-metastatic B16BL6 melanoma and two sublines of liver-metastatic RAW117 large cell lymphoma, were injected i.v., and the trafficking of these cells was noninvasively determined. All sublines tested accumulated in the lungs immediately after injection, presumably because the lungs were the first organ passed through after i.v. injection. The elimination of RAW117 cells from the lungs, however, was fast compared with that of B16BL6 cells. The latter showed a release rate from the lungs of less than 1%/min, whereas that of RAW117 cells was greater than 2%/min. Reflecting the elimination from lungs, RAW117 cells accumulated in the liver in a time-dependent manner. Biodistribution of metastatic cells was also analyzed by whole-body autoradiography after injection of 5-[125I]iodo-2'-deoxyuridine-labeled cells, using a bioimaging analyzer system. The method is invasive; however, it enables a precise determination of the biodistribution of metastatic cells. Bioimaging analyzer system analysis also showed the organ-specific accumulation of these metastatic cells. Furthermore, colonized distribution of B16BL6 cells in the lungs and that of RAW117 cells in the liver were observed. The present data suggest that the trafficking of metastatic tumor cells greatly influences the organ specificity of cancer metastasis.


Repair strength of etched vs silica-coated metal-ceramic and all-ceramic restorations.
The purpose of this in vitro study was to examine shear bond strengths of composite resin to metal-exposed porcelain-fused-to-metal (PFM) and all-ceramic restorations after silica coating or etching with 5% hydrofluoric acid (HF). Specimens were fabricated for each of the following groups: two all-ceramic materials [a feldspathic porcelain (Vita Mark II) and a leucite-reinforced glass-ceramic (IPS Empress)], and one noble metal-ceramic (Orplid Keramik I alloy; Vita VMK 68 N felspathic veneer ceramic). These groups were repaired with resin composites after different pretreatment methods. In one metal-ceramic subgroup the surface exhibited a 50% metal and 50% ceramic exposure. In the silica-coating groups, the specimen surfaces were air abraded with silica acid-modified Al2O3 (CoJet Sand) and treated corresponding to the porcelain repair with resin composite. For control groups, the surfaces were etched with 5% HF for 60 seconds and treated in the same way as the silica-coated groups. After 24 hours of storage (distilled water, 37 degrees C) and an additional 24 hours of thermocycling (1150 x 5 degrees C/55 degrees C) the specimens were debonded using a shear bond strength test (n = 15). In all groups the silica coat repair achieved equal or significantly higher bond strengths than did the etching technique (p < 0.05, Mann-Whitney U test). In the metal-exposed group, the mean bond strength increased from 7.3 MPa to 16.3 MPa following the silica-coat repair. Results indicated that silica coating represents a suitable treatment for the intraoral repair of the materials tested in the present study.


Crystal structure of the yeast MATalpha2/MCM1/DNA ternary complex.
The structure of a complex containing the homeodomain repressor protein MATalpha2 and the MADS-box transcription factor MCM1 bound to DNA has been determined by X-ray crystallography at 2.25 A resolution. It reveals the protein-protein interactions responsible for cooperative binding of MATalpha2 and MCM1 to DNA. The otherwise flexible amino-terminal extension of the MATalpha2 homeodomain forms a beta-hairpin that grips the MCM1 surface through parallel beta-strand hydrogen bonds and close-packed, predominantly hydrophobic, side chains. DNA bending induced by MCM1 brings the two proteins closer together, facilitating their interaction. An unusual feature of the complex is that an eight-amino-acid sequence adopts an alpha-helical conformation in one of two copies of the MATalpha2 monomer and a beta-strand conformation in the other. This 'chameleon' sequence of MATalpha2 may be important for recognizing natural operator sites.


Neuroimaging Correlates of Resilience to Traumatic Events-A Comprehensive Review.
Improved understanding of the neurobiological correlates of resilience would be an important step toward recognizing individuals at risk of developing post-traumatic stress disorder (PTSD) or other trauma-related diseases, enabling both preventative measures and individually tailored therapeutic approaches. Studies on vulnerability factors allow drawing conclusions on resilience. Structural changes of cortical and subcortical structures, as well as alterations in functional connectivity and functional activity, have been demonstrated to occur in individuals with PTSD symptoms. Relevant areas of interest are hippocampus, amygdala, insula, anterior cingulate cortex, and prefrontal cortex, as well as related brain networks, such as the default-mode, salience, and central executive network. This review summarizes the existing literature and integrates findings from cross-sectional study designs with two-group designs (trauma exposed individuals with and without PTSD), three-group designs (with an additional group of unexposed, healthy controls), twin-studies and longitudinal studies. In terms of structural findings, decreased hippocampal volume in PTSD individuals might be either a vulnerability factor or a result of trauma exposure, or both. Reduced anterior cingulate cortex and prefrontal cortex volumes seem to be predisposing factors for increased vulnerability. Regarding functional connectivity, increased amygdala connectivity has been demonstrated selectively in PTSD individuals, as well as increased default-mode-network and salience network connectivity. In terms of functional activity, increased amygdala and anterior cingulate cortex activities, and decreased prefrontal cortex activity as a response to external stimuli have been associated with higher vulnerability. Increased prefrontal cortex activity seemed to be a protective factor. Selecting adequate study designs, optimizing the diagnostic criteria, as well as differentiating between types of trauma and accounting for other factors, such as gender-specific differences, would be well-served in future research. Conclusions on potential preventative measures, as well as clinical applications, can be drawn from the present literature, but more studies are needed.


Bacteriophytochrome from Magnetospirillum magneticum affects phototactic behavior in response to light.
Phytochromes are a class of photoreceptors found in plants and in some fungi, cyanobacteria, and photoautotrophic and heterotrophic bacteria. Although phytochromes have been structurally characterized in some bacteria, their biological and ecological roles in magnetotactic bacteria remain unexplored. Here, we describe the biochemical characterization of recombinant bacteriophytochrome (BphP) from magnetotactic bacteria Magnetospirillum magneticum AMB-1 (MmBphP). The recombinant MmBphP displays all the characteristic features, including the property of binding to biliverdin (BV), of a genuine phytochrome. Site-directed mutagenesis identified that cysteine-14 is important for chromophore covalent binding and photoreversibility. Arginine-240 and histidine-246 play key roles in binding to BV. The N-terminal photosensory core domain of MmBphP lacking the C-terminus found in other phytochromes is sufficient to exhibit the characteristic red/far-red-light-induced fast photoreversibility of phytochromes. Moreover, our results showed MmBphP is involved in the phototactic response, suggesting its conservative role as a stress protectant. This finding provided us a better understanding of the physiological function of this group of photoreceptors and photoresponse of magnetotactic bacteria.


The prognostic significance of K-ras, p53, and APC mutations in colorectal carcinoma.
Accumulation of molecular alterations, including mutations in Kirsten-ras (K-ras), p53, and adenomatous polyposis coli (APC), contribute to colorectal carcinogenesis. Our group has previously characterised a panel of sporadic colorectal adenocarcinomas for mutations in these three genes and has shown that p53 and K-ras mutations rarely occur in the same colorectal tumour. This suggests that mutations in these genes are on separate pathways to colorectal cancer development and may influence patient prognosis independently. To correlate the presence or absence of mutations in K-ras, p53, and APC with survival in a cohort of colorectal cancer patients. A series of 107 inpatients treated surgically for colorectal cancer in Tayside, Scotland between November 1997 and December 1999. Colorectal tumours were characterised for mutations in K-ras, p53, and APC. Kaplan-Meier survival curves were constructed using overall survival and disease specific survival as the primary end points. Patient survival was analysed using the log rank test and Cox proportional hazards model. Patients with K-ras mutations had significantly poorer overall survival than patients without K-ras mutations (p = 0.0098). Multivariate analysis correcting for Dukes' stage, age, and sex confirmed this (hazard ratio 2.9 (95% confidence interval 1.4-6.2); p = 0.0040). K-ras mutations were also significantly associated with poorer disease specific survival. The presence of APC and p53 mutations did not affect survival in this cohort of patients (p = 0.9034 and p = 0.8290, respectively). Our data indicate that the presence of K-ras mutations predicts poor patient prognosis in colorectal cancer, independently of tumour stage.


Effect of mass shootings on gun sales-A 20-year perspective.
Granular data on gun sales has been historically difficult to obtain. In 2016, California (CA) made monthly data from 1996 to 2015 publically available. Control charts are a method to analyze how a process changes over time in response to nonroutine events. We utilized this technique to study the impact of US mass shootings on CA gun sales. Monthly gun sales were provided by the CA Department of Justice and monthly fatalities from the CDC Wonder Death Certificate Registry. Mass shooting events were obtained from after-action reports, news media, and court proceedings. Time-ordered data were analyzed with control charts with 95% confidence intervals (upper control limit, lower control limit) using QiMacros. Individual gun sales of 9,917,811 occurred in CA with a median monthly rate of 41,324 (range, 20,057-132,903). A median of 263 people lost their lives monthly from firearms (124 homicides, 128 suicides), totaling 53,975 fatalities from 1999 to 2015. Fifteen of 21 current deadliest mass shootings occurred during this study period with 40% from 2012 to 2015. Also, 36 school shootings occurred during the study (mean, 5 deaths; range, 0-33; 6 injuries; range, 0-23) with 31% in 2012 to 2015 at rate of 3 events/year versus 1.4 events/year in the 17 prior years (p < 0.05). Sales were generally consistent from 1996 to 2011 (except post-Columbine, Col). Starting in 2011, sales exceeded the 95% predicted upper control limit every single month. Before October 2011, there was no statistically significant sustained effect of mass shootings on sales (except Col); however, since a statistically significant proportional spike in sales occurred in the months immediately following every single deadliest mass shooting event. Every year since 2012, CA has strengthened gun laws in response to mass shootings yet sales have risen immediately preceding enactment of these laws each January. Gun sales are more frequent since 2012, with an additional increase following both mass shootings and legislative changes enacted in response to these shootings. Epidemiology, level III.


Exploring the Effects of Cyanidin-3-O-Glucoside on Type 2 Diabetes Mellitus: Insights into Gut Microbiome Modulation and Potential Antidiabetic Benefits.
Berries and their functional components have been put forward as an alternative to pharmacological treatments of type 2 diabetes mellitus (T2DM), and more attention has been paid to the gut microbiome in the pathophysiology of T2DM. Thus, we tried to examine the metabolic impact of red bayberry-derived cyanidin-3-O-glucoside (C3G) and investigate whether the antidiabetic effects of C3G were associated with the gut microbiome. As a result, C3G administration was found to reduce blood glucose levels of diabetic db/db mice, accompanied by increased levels of glucagon-like peptide (GLP-1) and insulin. Moreover, 16S rRNA analysis showed that the dominant microbiota modulated by C3G were pivotal in the glucose metabolism. Furthermore, the modulation of C3G on metabolic activities of gut bacteria leads to an increase in intestinal levels of key metabolites, particularly short-chain fatty acids. This contribution helps in promoting the secretion of GLP-1, which in turn increases insulin release with the purpose of reducing blood glucose levels. Overall, these findings may offer new thoughts concerning C3G against metabolic disorders in T2DM.


Childhood reproductive hormone levels after pediatric hematopoietic stem cell transplantation in relation to adult testicular function.
Longitudinal assessment of testicular function after pediatric hematopoietic stem cell transplantation (HSCT) is needed to guide clinical follow-up. We investigated dynamics in male reproductive hormones after pediatric HSCT, focusing on pubertal timing and associations with testosterone deficiency and azoospermia in adulthood. This retrospective, longitudinal study included 39 survivors median 19 years after pediatric HSCT. Serum concentrations of LH, testosterone, FSH, and inhibin B from the time of HSCT, during puberty, and into adulthood were analyzed. Pubertal timing (rise in LH and testosterone) was compared to a reference cohort of 112 healthy boys. Associations between reproductive hormone levels during puberty and adult testicular function (including semen quality) were investigated. Pubertal induction with testosterone was needed in 6/26 patients who were prepubertal at HSCT. In the remaining patients, pubertal timing was comparable to the reference cohort. However, 9/33 patients (without pubertal induction) developed testosterone deficiency in early adulthood, which was associated with higher LH levels from age 14 to 16 years. Azoospermia in adulthood was found in 18/26 patients without testosterone substitution. Higher FSH and lower inhibin B levels from mid-pubertal age were associated with azoospermia in adulthood, in patients being prepubertal at HSCT. Our results indicate a substantial risk of deterioration in testicular function after pediatric HSCT, despite normal pubertal timing. Although reproductive hormone levels from mid-puberty indicated adult testicular function, prolonged follow-up into adulthood is needed in these patients, including clinical examination, reproductive hormone analysis, and semen sample for patients interested in their fertility potential.


Screening heteroatom distributions in zeotype materials using an effective Hamiltonian approach: the case of aluminogermanate PKU-9.
We introduce a method to allow the screening of large configurational spaces of heteroatom distributions in zeotype materials. Based on interatomic potential calculations of configurations containing up to two heteroatoms per cell, we parameterize an atomistic effective Hamiltonian to describe the energy of multiple substitutions, with consideration of both short- and long-range interactions. Then, the effective Hamiltonian is used to explore the full configurational space at other compositions, allowing the identification of the most stable structures for further analysis. We illustrate our approach with the aluminogermanate PKU-9, where we show that increasing the aluminium concentration changes the likely siting of Al, in agreement with experiment.


[Prevention of side effects and complications after operation for partial ileal bypass].
Side effects and complications of the application of partial ileal bypass used for dislipidemia were analyzed in 162 patients with atherosclerosis. It was shown, that the partial ileal bypass operation could lead to the development of series of undesirable side effects such as diarrhea, hypovitaminosis B12, off-state intestine enteritis. The application of modification of partial ileal bypass such as formation of ileo-ileoanastomosis 5-6 cm long near ileocecal valve with the maintenance of its functions disposed the diarrhea and minimized the risk of the development of hypovitaminosis B12 after operation. It is possible to prevent the development of enteritis of off-state loop of the small intestine by using microanastomosis between off-state and functioning iliac intestine. The partial ileal bypass operation didn't influence on body weight, wouldn't increase the risk of stone formation in the gallbladder and kidneys. The risk of the development of hypovitaminosis B12 is minimal after operation.


Macrophage migration inhibitory factor is expressed by equine conceptuses and endometrium.
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine expressed by a wide range of tissues, which has been implicated to be involved in reproduction. Relative abundance of MIF mRNA in conceptus and endometrial tissue was assessed using real-time RT-PCR. Western blot analysis and immunohistochemistry were used to detect MIF protein expression. MIF transcript abundance was lowest in conceptuses obtained 16 days after ovulation, while the remaining stages of conceptus development that were analysed showed relatively constant expression levels. Migration inhibitory factor expression localized to trophectoderm cells, while capsular material was void of MIF immunoreactivity. Throughout the oestrous cycle, no clear statistically significant cycle-dependent expression pattern could be observed. During early pregnancy, the highest mRNA transcript levels were detected 16 days after ovulation. Pregnancy status did not affect MIF mRNA expression. Using immunohistochemistry, MIF protein expression was primarily localized in luminal and glandular epithelial cells, while stromal cells displayed weaker immunoreactivity. Taken together, we suggest that MIF is part of the molecular repertoire that contributes to normal endometrial function. The detailed functional significance of MIF expression in equine endometrium and pre-implantation stages of conceptus development remains to be determined.


Profile and factors determining outcome in a cohort of cystic fibrosis patients seen at the Aga Khan University Hospital, Karachi, Pakistan.
Cystic fibrosis is the most common potentially lethal autosomal recessive, genetic disease associated with pulmonary and pancreatic insufficiency. It is caused by variations in the CFTR (cystic fibrosis transmembrane regulator) gene. The most common mutation in the CFTR gene designated DeltaF508, is found in only 33 per cent of CF patients in Pakistan. The variability in presentation and clinical severity of disease may be a function of genotypic-phenotypic factors. Our aim was to attempt to define the disease in this region and to lay the ground work for future mutational analysis. This study was a retrospective chart review was conducted to identify cystic fibrosis patients seen at the Aga Khan University Hospital over a 10-year period. Our study identified 56 patients diagnosed by a pilocarpine iontophoresis sweat test. A chart review was then done to look at the various clinical profiles. 58.3 per cent of our patients presented in the first 6 months of life supporting the hypothesis that CF may be a severe disease in Asians with an earlier age of presentation. Most of the patients (80.6 per cent) presented with pulmonary problems while 83.9 per cent had failure to thrive. The most frequently isolated pathogen was Pseudomonas aeruginosa in 87.5 per cent of the patients tested. 70 per cent of the patients died in the first year of life. The clinical parameters studied suggest a severe form of CF in Pakistani patients and provides a foundation for future studies to define genotype/phenotype correlations of the specific mutations involved in Pakistani CF patients.


Transforming growth factor β1 regulates the expression of CCN2 in human keratinocytes via Smad-ERK signalling.
Connective tissue growth factor (CCN2/CTGF) and transforming growth factor β1 (TGF-β1) are important regulators of skin wound healing, but controversy remains regarding their expression in epithelial cell lineages. Here, we investigate the expression of CCN2 in keratinocytes during reepithelialisation and its regulation by TGF-β1. CCN2 was detected in the epidermis of healing full-thickness porcine wounds. Human keratinocytes were incubated with or without 10 ng/ml TGF-β1, and signalling pathways were blocked with 10-μM SIS3 or 20-μM PD98059. Semi-quantitative real-time PCR was used to study CCN2 mRNA expression, and western blot was used to measure CCN2, phosphorylated-ERK1/2, ERK1/2, phosphorylated-Smad3 and Smad2/3 proteins. CCN2 was transiently expressed in neoepidermis at the leading edge of the wound in vivo. In vitro, CCN2 expression was induced by TGF-β1 at 2 hours (7·5 ± 1·9-fold mRNA increase and 3·0 ± 0·6-fold protein increase) and 12 hours (5·4 ± 1·9-fold mRNA increase and 3·3 ± 0·6-fold protein increase). Compared with inhibiting the SMAD pathway, inhibiting the mitogen-activated protein kinase (MAPK) pathway was more effective in reducing TGF-β1-induced CCN2 mRNA and protein expression. Inhibition of the MAPK pathway had minimal impact on the activity of the SMAD pathway. CCN2 is expressed in keratinocytes in response to tissue injury or TGF-β1. In addition, TGF-β1 induces CCN2 expression in keratinocytes through the ras/MEK/ERK pathway. A complete understanding of CCN2 expression in keratinocytes is critical to developing novel therapies for wound healing and cutaneous malignancy.


How effective are trained dogs at alerting their owners to changes in blood glycaemic levels?: Variations in performance of glycaemia alert dogs.
Domestic dogs are trained to a wide variety of roles including an increasing number of medical assistance tasks. Glycaemia alert dogs are reported to greatly improve the quality of life of owners living with Type 1 diabetes. Research into their value is currently sparse, on small numbers of dogs and provides conflicting results. In this study we assess the reliability of a large number of trained glycaemic alert dogs at responding to hypo- and hyper-glycaemic (referred to as out-of-range, OOR) episodes, and explore factors associated with variations in their performance. Routine owner records were used to assess the sensitivity and specificity of each of 27 dogs, trained by a single UK charity during almost 4000 out-of-range episodes. Sensitivity and positive predictive values are compared to demographic factors and instructors' ratings of the dog, owner and partnership. Dogs varied in their performance, with median sensitivity to out-of-range episodes at 70% (25th percentile = 50, 75th percentile = 95). To hypoglycaemic episodes the median sensitivity was 83% (66-94%) while to hyperglyaemic episodes it was 67% (17-91%). The median positive predictive value (PPV) was 81% (68-94%), i.e. on average 81% of alerts occurred when glucose levels were out of target range. For four dogs, PPV was 100%. Individual characteristics of the dog, the partnership and the household were significantly associated with performance (e.g., whether the dog was previously a pet, when it was trained, whether its partner was an adult or child). The large sample shows that the individual performance of dogs is variable, but overall their sensitivity and specificity to OOR episodes are better than previous studies suggest. Results show that optimal performance of glycaemic alert dogs depends not only on good initial and ongoing training, but also careful selection of dogs for the conditions in which they will be working.


PtdIns(4,5)P2 and PtdIns(3,4,5)P3 dynamics during focal adhesions assembly and disassembly in a cancer cell line.
Focal adhesions (FAs) are large assemblies of proteins that mediate intracellular signals between the cytoskeleton and the extracellular matrix (ECM). The turnover of FA proteins plays a critical regulatory role in cancer cell migration. Plasma membrane lipids locally generated or broken down by different inositide kinases and phosphatase enzymes to activate and recruit proteins to specific regions in the plasma membrane. Presently, little attention has been given to the use of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and Phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) fluorescent biosensors in order to determine the spatiotemporal organisation of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 within and around or during assembly and disassembly of FAs. In this study, specific biosensors were used to detect PtdIns(4,5)P2, PtdIns(3,4,5)P3, and FAs proteins conjugated to RFP/GFP in order to monitor changes of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 levels within FAs. We demonstrated that the localisation of PtdIns(4,5)P2 and PtdIns(3,4,5)P3 were moderately correlated with that of FA proteins. Furthermore, we demonstrate that local levels of PtdIns(4,5)P2 increased within FA assembly and declined within FA disassembly. However, PtdIns(3,4,5)P3 levels remained constant within FAs assembly and disassembly. In conclusion, this study shows that PtdIns(4,5)P2 and PtdIns(3,4,5)P3 localised in FAs may be regulated differently during FA assembly and disassembly.


Monophyletic group of unclassified γ-Proteobacteria dominates in mixed culture biofilm of high-performing oxygen reducing biocathode.
Several mixed microbial communities have been reported to show robust bioelectrocatalysis of oxygen reduction over time at applicable operation conditions. However, clarification of electron transfer mechanism(s) and identification of essential micro-organisms have not been realised. Therefore, the objective of this study was to shape oxygen reducing biocathodes with different microbial communities by means of surface modification using the electrochemical reduction of two different diazonium salts in order to discuss the relation of microbial composition and performance. The resulting oxygen reducing mixed culture biocathodes had complex bacterial biofilms variable in size and shape as observed by confocal and electron microscopy. Sequence analysis of ribosomal 16S rDNA revealed a putative correlation between the abundance of certain microbiota and biocathode performance. The best performing biocathode developed on the unmodified graphite electrode and reached a high current density for oxygen reducing biocathodes at neutral pH (0.9 A/m(2)). This correlated with the highest domination (60.7%) of a monophyletic group of unclassified γ-Proteobacteria. These results corroborate earlier reports by other groups, however, higher current densities and higher presence of these unclassified bacteria were observed in this work. Therefore, members of this group are likely key-players for highly performing oxygen reducing biocathodes.


High Dietary Acid Load Predicts ESRD among Adults with CKD.
Small clinical trials have shown that a reduction in dietary acid load (DAL) improves kidney injury and slows kidney function decline; however, the relationship between DAL and risk of ESRD in a population-based cohort with CKD remains unexamined. We examined the association between DAL, quantified by net acid excretion (NAEes), and progression to ESRD in a nationally representative sample of adults in the United States. Among 1486 adults with CKD age≥20 years enrolled in the National Health and Nutrition Examination Survey III, DAL was determined by 24-h dietary recall questionnaire. The development of ESRD was ascertained over a median 14.2 years of follow-up through linkage with the Medicare ESRD Registry. We used the Fine-Gray competing risks method to estimate the association of high, medium, and low DAL with ESRD after adjusting for demographics, nutritional factors, clinical factors, and kidney function/damage markers and accounting for intervening mortality events. In total, 311 (20.9%) participants developed ESRD. Higher levels of DAL were associated with increased risk of ESRD; relative hazards (95% confidence interval) were 3.04 (1.58 to 5.86) for the highest tertile and 1.81 (0.89 to 3.68) for the middle tertile compared with the lowest tertile in the fully adjusted model. The risk of ESRD associated with DAL tertiles increased as eGFR decreased (P trend=0.001). Among participants with albuminuria, high DAL was strongly associated with ESRD risk (P trend=0.03). In conclusion, high DAL in persons with CKD is independently associated with increased risk of ESRD in a nationally representative population.


Two-dimensional Mo1.33C MXene with divacancy ordering prepared from parent 3D laminate with in-plane chemical ordering.
The exploration of two-dimensional solids is an active area of materials discovery. Research in this area has given us structures spanning graphene to dichalcogenides, and more recently 2D transition metal carbides (MXenes). One of the challenges now is to master ordering within the atomic sheets. Herein, we present a top-down, high-yield, facile route for the controlled introduction of ordered divacancies in MXenes. By designing a parent 3D atomic laminate, (Mo2/3Sc1/3)2AlC, with in-plane chemical ordering, and by selectively etching the Al and Sc atoms, we show evidence for 2D Mo1.33C sheets with ordered metal divacancies and high electrical conductivities. At ∼1,100 F cm-3, this 2D material exhibits a 65% higher volumetric capacitance than its counterpart, Mo2C, with no vacancies, and one of the highest volumetric capacitance values ever reported, to the best of our knowledge. This structural design on the atomic scale may alter and expand the concept of property-tailoring of 2D materials.


Polaron dynamics in anisotropic Holstein-Peierls systems.
Polaron dynamics in anisotropic organic molecular semiconductors is theoretically investigated and simulated in the framework of a semi-classical Holstein-Peierls model. Our computational protocol is presented and applied to studies of a two-dimensional molecular crystal. The intermolecular (Peierls) parameters for a particular crystal direction are systematically changed in order to study the effect of anisotropy in the system. The usefulness of this methodology is highlighted by studying the polaron dynamics on a picosecond timescale, which provides a microscopic insight into the influence of the interplay between different intramolecular parameters on the charge transport mechanism. Our results show that the polaron mobility is substantially reduced in going from an anisotropic to an isotropic relationship between the Peierls parameters for different directions in the crystal. Interestingly, the molecular charge distribution presents three different signatures corresponding to a one-dimensional polaron, a two-dimensional polaron, and an intermediate state for which the polaron localization depends on the degree of anisotropy. Importantly, the two-dimensional polaron, which is present in the essentially isotropic system, is immobile whereas the other two types of polarons are mobile. This, in order for polaron transport to occur in a two-dimensional molecular based system, this system has to be anisotropic.


Oxidative biotransformation of stemofoline alkaloids.
Biotransformations of stemofoline (1a), (2'S)-hydroxystemofoline (2a), (11Z)-1',2'-didehydrostemofoline (3a) and stemocurtisine (4) were studied through fermentation with Cunninghamella elegans TISTR 3370. Three new stemofoline derivatives; 6 R-hydroxystemofoline (1b), (2'S, 6 R)-dihydroxystemofoline (2b) and (11Z,6R)-1',2'-didehydro-6-hydroxystemofoline (3b), together with the known compound 1',2'-didehydrostemofoline-N-oxide (3c), were produced by C-hydroxylation and N-oxidation reactions. Stemocurtisine was not biotransformed under these conditions. The transformed product 1b was four times more potent (IC50 = 11.01 ± 1.49 µM) than its precursor 1a (IC50 = 45.1 ± 5.46 µM) as an inhibitor against acetylcholinesterase.


[A case of obsessive symptoms in Huntington's disease].
Recently, some authors have postulated the existence of the so-called <<obsessive spectrum>>. This would include disorders that have the common point of the presence of repetitive thoughts and actions, which may either have a <<compulsive>> or <<impulsive>> nature. Certain neurological disorders with repetitive movements have also been grouped within this spectrum, including some forms of epilepsy, Parkinson's disease, Sydenham's Chorea or Huntington's disease. There is evidence that physiopathological connections may exist between some of these conditions. A case of a patient with Huntington's Chorea with obsessive signs and symptoms is presented. The patient is a 50 year old male, diagnosed of Huntington's Chorea who is being treated with 25 mg/day of clozapine and 10 mg/day of clorazepate. The patient refused to eat certain foods for <<fear of choking>>. He began to display other obsessive behaviors such as refusing to touch objects that might have been touched by others, and developed ritual checking methods. Treatment based on the administration of 40 mg/day of paroxetine was begun. With this treatment the compulsive symptoms have disappeared, as has the fear of choking. However, the choreic movements typical of his condition persist and the signs and symptoms associated with a process of dementia are becoming increasingly evident. It is concluded that the case described may well be a good example of obsessive spectrum, and that the underlying physio-pathology should be studied.