Is there any correlation between the elevated plasma levels and gene variations of factor VIII in Turkish thrombosis patients?
We investigated factor VIII (FVIII) gene mutations in 20 thrombosis patients with high level of FVIII and 20 control healthy participants. Blood samples were used for the determination of FVIII levels using static timing analyze (STA) kits. Informed consent forms were collected from all participants. Factor VIII level was 237 ± 46 IU/dL in patients group; however, it was 122 ± 38 IU/dL in healthy control participants. Isolated genomic DNAs were screened using 37 pairs of primers covering promoter region and 26 exons of FVIII gene. Single-strand conformation analysis (SSCA) technique was performed for polymorphism/mutation analyses. We observed polymorph patterns in exon 6, exon 13, exon 14F, exon 19, and exon 25 regions. However, we found no evidence of an association between observed single nucleotide polymorphisms and high thrombosis levels. In conclusion, observed exons polymorphisms do not seem to be associated with a venous thromboembolism.


A constitutive model for smooth muscle including active tone and passive viscoelastic behaviour.
A new constitutive model for the biomechanical behaviour of smooth muscle tissue is proposed. The active muscle contraction is accomplished by the relative sliding between actin and myosin filaments, comprising contractile units in the smooth muscle cells. The model includes a chemical part, governing the cross-bridge (myosin head) cycling, that is responsible for the filament sliding. The number of activated cross-bridges govern the contractile force generated and also the contraction speed. A strain-energy function is used to describe the mechanical behaviour of the smooth muscle tissue. Besides the active contractile apparatus, the mechanical model also incorporates a passive viscoelastic part. The constitutive model was calibrated with respect to experiments on smooth muscle tissue from swine carotid artery and guinea pig taenia coli, in terms of isometric and isotonic tensile test results. The model was fully able to reproduce the experimental results.


Time to Clinically Relevant Fracture Risk Scores in Postmenopausal Women.
Clinical practice guidelines recommend use of fracture risk scores for screening and pharmacologic treatment decisions. The timing of occurrence of treatment-level (according to 2014 National Osteoporosis Foundation guidelines) or screening-level (according to 2011 US Preventive Services Task Force guidelines) fracture risk scores has not been estimated in postmenopausal women. We conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores in postmenopausal women aged 50 years and older, prior to receipt of pharmacologic treatment and prior to first hip or clinical vertebral fracture. In 54,280 postmenopausal women aged 50 to 64 years without a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of rare incidence of treatment-level scores. In 6096 women who had FRAX scores calculated with bone mineral density, the estimated unadjusted time to treatment-level FRAX ranged from 7.6 years (95% confidence interval [CI], 6.6-8.7) for those aged 65 to 69, to 5.1 years (95% CI, 3.5-7.5) for those aged 75 to 79 at baseline. Of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years. Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.


Influences of statins on glucose tolerance in patients with type 2 diabetes mellitus.
Atorvastatin is frequently administered for the treatment of hypercholesterolemia associated with type 2 diabetes mellitus. However, a marked deterioration of glycemic control has been reported in some patients treated with atorvastatin. No study has been done to determine whether atorvastatin adversely affects glycemic control. In this study, we retrospectively compared an atorvastatin-treated group (Group A, n = 76) with a pravastatin-treated group (Group P, n = 78) to examine the effects of the 2 statins on glycemic control from the onset of administration to 3 months thereafter. No change occurred in the antidiabetic drug dose in 62 patients of Group A and 68 patients of Group P. In those patients, arbitrary blood glucose levels increased from 147 +/- 50 (mean +/- SD) mg/dL to 177 +/- 70 mg/dL in Group A and from 140 +/- 38 mg/dL to 141 +/- 32 mg/dL in Group P. HbA(1c) increased from 6.8 +/- 0.9% to 7.2 +/- 1.1% in Group A and from 6.9 +/- 0.9% to 6.9 +/- 1.0% in Group P. The increase was significant only in Group A, and the extent of the increase was also significantly greater in Group A. These results suggest a predisposition to a deterioration of glycemic control in type 2 diabetic patients treated with atorvastatin.


Experiences of living with dementia: qualitative content analysis of semi-structured interviews.
To describe people's experiences of living with dementia in Iran. A knowledge gap exists regarding the experiences of living with dementia in nonWestern contexts. This gap may be especially apparent within the Iranian context, where dementia research is relatively new. Deeper understanding about context-related experiences of dementia is a prerequisite for nurses' ability to provide adequate and meaningful care. Qualitative, cross-sectional design. Qualitative content analysis of semi-structured interviews with people living with dementia in urban Iran (six women and nine men; 60-87 years old). The participants experienced their condition as a state of forgetfulness that was accompanied by losses and dependency on others. They wanted to feel good about themselves and feel important, but they continually struggled with matters such as a loss of accountability, feelings of futility and the frustration of others. Economic dependency and a lack of economic resources were sources of feelings of futility. Experiences of living with dementia in Iran included a substantial struggle to stay connected to the social world and to deal with dramatic life changes, aspects of living with dementia that seem to be universal. However, the feelings of financial burden and the experience of being nagged for their shortfalls by family members have seldom been described in other studies and seem to represent a cultural aspect of their experience. The results of the study call for further nursing efforts in supporting people living with dementia in their struggle with their altered lives and in retaining their connections to everyday life. Furthermore, their family members might benefit from specific nursing interventions including information about dementia and advice on how to help the family members with dementia to interact with others while exercising their individual strengths.


A new minimally invasive transsartorial approach for periacetabular osteotomy.
A new minimally invasive transsartorial approach for the Bernese periacetabular osteotomy was developed. We investigated whether this technique was safe and successful with regard to minimizing tissue trauma and, more importantly, whether it was possible to obtain optimal reorientation of the acetabulum. Our experience with this approach was retrospectively assessed by means of database inquiry and the evaluation of radiographs. We assessed ninety-four procedures performed between April 2003 and August 2005 to determine perioperative and early postoperative outcome measures, the achieved acetabular reorientation, and hip joint survival. The mean duration of surgery was 73.1 minutes, the median perioperative blood loss was 250 mL, and the mean reduction in the hemoglobin level was 33 g/L. Blood transfusion was required following 3% of the procedures. No injuries to the great vessels or nerves, arterial thromboses, unintended extension of the osteotomy, or deep infections occurred. The postoperative acetabular reorientation was assessed by measuring the center-edge and acetabular index angles, the medians of which were 34 degrees and 3 degrees , respectively. With total hip arthroplasty as the end point, the hip joint survival rate was estimated to be 98% at 4.3 years. Osteotomy with use of this minimally invasive transsartorial approach appears to be a safe, relatively short surgical procedure associated with a relatively small amount of blood loss and minimal transfusion requirements. Optimal acetabular reorientation can be achieved with this technique.


mRNA and microRNA expression profiles in circulating tumor cells and primary tumors of metastatic breast cancer patients.
Molecular characterization of circulating tumor cells (CTC) holds great promise. Unfortunately, routinely isolated CTC fractions currently still contain contaminating leukocytes, which makes CTC-specific molecular characterization extremely challenging. In this study, we determined mRNA and microRNA (miRNA) expression of potentially CTC-specific genes that are considered to be clinically relevant in breast cancer. CTCs were isolated with the epithelial cell adhesion molecule-based CellSearch Profile Kit. Selected genes were measured by real-time reverse transcriptase PCR in CTCs of 50 metastatic breast cancer patients collected before starting first-line systemic therapy in blood from 53 healthy blood donors (HBD) and in primary tumors of 8 of the patients. The molecular profiles were associated with CTC counts and clinical parameters and compared with the profiles generated from the corresponding primary tumors. We identified 55 mRNAs and 10 miRNAs more abundantly expressed in samples from 32 patients with at least 5 CTCs in 7.5 mL of blood compared with samples from 9 patients without detectable CTCs and HBDs. Clustering analysis resulted in 4 different patient clusters characterized by 5 distinct gene clusters. Twice the number of patients from cluster 2 to 4 had developed both visceral and nonvisceral metastases. Comparing transcript levels in CTCs with those measured in corresponding primary tumors showed clinically relevant discrepancies in estrogen receptor and HER2 levels. Our study shows that molecular profiling of low numbers of CTCs in a high background of leukocytes is feasible and shows promise for further studies on the clinical relevance of molecular characterization of CTCs.


Microfluidic sorting of arbitrary cells with dynamic optical tweezers.
Optical gradient forces generated by fast steerable optical tweezers are highly effective for sorting small populations of cells in a lab-on-a-chip environment. The presented system can sort a broad range of different biological specimens by an automated optimisation of the tweezer path and velocity profile. The optimal grab positions for subsequent trap and cell displacements are estimated from the intensity of the bright field image, which is derived theoretically and proven experimentally. We exhibit rapid displacements of 2 μm small mitochondria, yeast cells, rod-shaped bacteria and 30 μm large protoplasts. Reliable sorting of yeast cells in a microfluidic chamber by both morphological criteria and by fluorescence emission is demonstrated.


Gathering Validity Evidence on an Internal Medicine Clerkship Multistep Exam to Assess Medical Student Analytic Ability.
Construct: The definition of clinical reasoning may vary among health profession educators. However, for the purpose of this paper, clinical reasoning is defined as the cognitive processes that are involved in the steps of information gathering, problem representation, generating a differential diagnosis, providing a diagnostic justification to arrive at a leading diagnosis, and formulating diagnostic and management plans. Background: Expert performance in clinical reasoning is essential for success as a physician, and has been difficult for clerkship directors to observe and quantify in a way that fosters the instruction and assessment of clinical reasoning. The purpose of this study was to gather validity evidence for the Multistep exam (MSX) format used by our medicine clerkship to assess analytical clinical reasoning abilities; we did this by examining the relationship between scores on the MSX and other external measures of clinical reasoning abilities. This analysis used dual process theory as the main theoretical framework of clinical reasoning, as well as aspects of Kane's validity framework to guide the selection of validity evidence for the investigation. We hypothesized that there would be an association between the MSX (a three-step clinical reasoning tool developed locally), and the USMLE Step 2 CS, as they share similar concepts in assessing the clinical reasoning of students. We examined the relationship between overall scores on the MSX and the Step 2 CS Integrated Clinical Encounter (ICE) score, in which the student articulates their reasoning for simulated patient cases, while controlling for examinee's internal medicine clerkship performance measures such as the NBME subject exam score and the Medicine clerkship OSCE score. Approach: A total 477 of 487 (97.9%) medical students, representing the graduating classes of 2015, 2016, 2017, who took the MSX at the end of each medicine clerkship (2012-2016), and Step 2 CS (2013-2017) were included in this study. Correlation analysis and multiple linear regression analysis were used to examine the impact of the primary explanatory variables of interest (MSX) onto the outcome variable (ICE score) when controlling for baseline variables (Medicine OSCE and NBME Medicine subject exam). Findings: The overall MSX score had a significant, positive correlation with the Step 2 CS ICE score (r = .26, P < .01). The overall MSX score was a significant predictor of Step 2 CS ICE score (ß = .19, P < .001), explaining an additional 4% of the variance of ICE beyond the NBME Medicine subject score and the Medicine OSCE score (Adjusted R2 = 13%). Conclusion: The stepwise format of the MSX provides a tool to observe clinical reasoning performance, which can be used in an assessment system to provide feedback to students on their analytical clinical reasoning. Future studies should focus on gaining additional validity evidence across different learners and multiple medical schools.


Overall Effectiveness of Rivaroxaban in Patients with Pulmonary Embolism.
Due to limited evidence on the impact of rivaroxaban in clinical practice, we compared the effectiveness of rivaroxaban versus standard of care (SOC) among patients in the Veterans Health Administration. Adult patients with continuous enrollment in a health plan with medical and pharmacy benefits for ≥12 months before and ≥3 months after an inpatient diagnosis of pulmonary embolism (PE) between October 1, 2011, and June 30, 2015, and a prescription claim for an anticoagulant during the index hospitalization, were included. SOC drugs were low-molecular-weight heparin, unfractionated heparin, and warfarin. Propensity score matching was used in comparing PE-related outcomes (recurrent venous thromboembolism, major bleeding, and death), hospital-acquired complications (HACs), health care resource utilization, and costs among patients receiving SOC versus rivaroxaban. We defined net clinical benefit as 1 minus the combined rate of PE-related outcomes and HACs. Among 6746 patients with PE, 208 received rivaroxaban, 4641 received SOC and 1897 received other anticoagulants. Most (95%) were male; 22% were black. After 1:3 propensity score matching, there were 203 rivaroxaban and 609 SOC patients. During the 90-day follow-up, rivaroxaban users had similar rates of PE-related outcomes, but fewer had experienced at least 1 HAC (10.3% vs 15.9%; P = 0.0506), resulting in better net clinical benefit (82.8% vs 71.1%; P = 0.001). Rivaroxaban users had fewer outpatient visits per patient (17.0 vs 19.9; P = 0.0005), a similar rehospitalization rate (0.2 vs 0.3; P = 0.084), lesser inpatient costs (US $3501 vs $6189; P < 0.0001), lesser inpatient costs and lesser total costs ($10,545 vs $14,192; P = 0.0002). When the sample was limited to patients with low-risk PE, we found similar patterns. Patients with PE prescribed rivaroxaban had similar PE-related outcomes, but fewer HACs and lesser total costs, than did patients on SOC.


[Collapsing Glomerulopathy Secondary to Anabolic Steroids for Bodybuilding: A Case Series].
The abuse of anabolic androgenic steroids (AAS) for competitive (and non-competitive) purposes for bodybuilding practice is increasingly common. The consequences of these substances on the various organs are only partially known. Cases of FSGS following the use of AAS have been reported in the literature, even with evolution to ESKD. We describe three cases of bodybuilding athletes who presented alterations in renal function indices after taking AAS for a long time. Three renal biopsies were performed with histological diagnosis of FSGS collapsing variant. We examine the lesions observed on histological examination. Two athletes had rapid progression of renal disease requiring replacement therapy. The third one continues conservative treatment for chronic renal failure. We discuss the risks related to the intake of doping substances and how bodybuilders are exposed to different causes of kidney damage: anabolic steroids, supplements, and a high-protein diet.


Factors impairing daytime performance in patients with sleep apnea/hypopnea syndrome.
Patients with sleep apnea/hypopnea syndrome commonly demonstrate impaired daytime performance. In a prospective study, 29 patients with sleep apnea/hypopnea syndrome were assessed polysomnographically to determine the relationship of cognitive performance and daytime sleepiness with sleep disruption, hypoxemia, and mood. Deterioration of cognitive performance correlated significantly with increasing severity of nocturnal breathing irregularity, magnitude of nocturnal hypoxemia, and extent of sleep disruption. Multiple regression analysis identified frequency of apneas plus hypopneas and of arousal and the extent of nocturnal hypoxemia as the variables most strongly associated with cognitive deficits. Anxiety and depression also contributed to this impairment. Objective daytime sleepiness was not significantly associated with nocturnal variables. This study showed that the frequency of breathing irregularities and the extent of both sleep disruption and nocturnal hypoxemia are important in determining daytime function in patients with sleep apnea/hypopnea syndrome. All of these factors should be considered when deciding which patients require treatment.


Telomere dynamics and cellular senescence: an emerging field in environmental and occupational toxicology.
There has been a steady output of epidemiological studies linking environmental and occupational exposures to altered telomere length, showing mainly positive associations with persistent organic pollutants, inverse association with cadmium and inconsistent results with arsenic and lead. A bell-shaped dose-response relationship has been observed for ionizing radiation with telomere shortening at a low dose. Long-term air pollution is associated with telomere shortening, whereas the short-term exposure studies have shown mixed results. There are surprisingly few studies on telomere dynamics in animals. Studies on telomere dynamics and senescence in target tissues of animal strains used in toxicology are warranted. Cell culture studies on ionizing radiation have shown mixed results on telomere length, whereas both telomerase activity and cellular senescence are increased. Studies on persistent organic pollutants indicate telomere shortening, decreased telomerase activity and increased cellular senescence. Cell culture studies on heavy metals and air pollution particles are inconsistent. There is no coherent relationship between exposures, oxidative stress, telomere length, telomerase activity and cellular senescence in experimental studies on environmental or occupational exposures. This may be due to differences in exposure levels (including dose rate), exposure time and models (i.e. cell types and animal strains). Guidelines are needed for best practices on assays for telomere dynamics and cellular senescence in toxicology. However, it deserves notice that experimental studies in cells and animals have revealed important information on the effects of environmental and occupational agents on the maintenance of telomeres and cellular senescence.


Quantification of glutamate and glutamine using constant-time point-resolved spectroscopy at 3 T.
Separate quantification of glutamate (Glu) and glutamine (Gln) using conventional MRS on clinical scanners is challenging. In previous work, constant-time point-resolved spectroscopy (CT-PRESS) was optimized at 3 T to detect Glu, but did not resolve Gln. To quantify Glu and Gln, a time-domain basis set was constructed taking into account metabolite T(2) relaxation times and dephasing from B(0) inhomogeneity. Metabolite concentrations were estimated by fitting the basis one-dimensional CT-PRESS diagonal magnitude spectra to the measured spectrum. This method was first validated using seven custom-built phantoms containing variable metabolite concentrations, and then applied to in vivo data acquired in rats exposed to vaporized ethanol and controls. Separate metabolite quantification revealed increased Gln after 16 weeks and increased Glu after 24 weeks of vaporized ethanol exposure in ethanol-treated compared with control rats. Without separate quantification, the signal from the combined resonances of Glu and Gln (Glx) showed an increase at both 16 and 24 weeks in ethanol-exposed rats, precluding the determination of the independent and differential contribution of each metabolite at each time.


Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats.
Protective effects of saturated hydrogen (H(2)) saline on cardiac ischaemia-reperfusion (I/R) injury have been demonstrated previously. This study was designed to show that hydrogen-rich saline is protective in preventing lung I/R injury in rats. Adult male Sprague-Dawley rats underwent 45 min occlusion of the right lung roots and 120 min reperfusion. Rats were divided randomly into three groups: sham-operated control group, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment (0.6 mmol/L, 0.5 ml/kg/d). Three days of intraperitoneal injection of hydrogen-rich saline before the reperfusion combined with immediate administration of hydrogen-rich saline after the reperfusion were performed. Following reperfusion, the lung tissue and the pulmonary artery was immediately obtained and the W/D ratio, pulmonary artery contraction and relaxation ability, H-E staining, TUNEL staining, caspase-3, MDA, 8-OHdG content and measurement of such biomarkers as WBC, CRP were measured or carried out. Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL. It is concluded that hydrogen-rich saline is a novel, simple, safe and effective method to attenuate pulmonary I/R injury.


Analysis of Cesarean section delivery at Nova Bila Hospital according to the Robson classification.
An increase in Cesarean section birth rate is evident worldwide, especially in developed and developing countries. Since this trend is rapidly gaining epidemic status with unpredictable consequences regarding the reproductive and overall women's health, there is a need for systematic collection and analysis of Cesarean section occurrence data. At this moment, there is no standardized, internationally accepted classification that would be easy to understand and simple to apply. In 2001, Robson Cesarean section classification in ten groups, which might satisfy good classification criteria, was published. In this paper, we have retrospectively collected and sorted the data on Cesarean section births from the "Dr. Fra Mato Nikolić" Croatian Hospital in Nova Bila, according to Robson classification, for the period from January 1st, 1998 to December 31st, 2007. During this period, 6603 women have given birth. Of these, 1010 opted for Cesarean sec- tion (15.30%). The largest group of women giving birth belongs to group 3 (multiparous, single pregnancy, head down, 37 weeks gestation age or more, spontaneous labor), where 49.74% of all the analyzed births belong. The largest group for those with Cesarean sections is group 5 (previous Cesarean section) with 26.93% of all the Cesarean sections. Our results are similar to the results of studies done elsewhere in the world. Robson classification identifies the risk groups with high Cesarean section percentage and is appropriate for long-term tracking and international comparison of the recognized increase of the Cesarean section trend.


Investigation of unilateral sensory or motor symptoms: frequency of neurological pathology depends on side of symptoms.
The records of 82 patients who had undergone inpatient neurological investigation for unilateral motor symptoms, sensory symptoms, or both, without definite neurological signs, were reviewed. Diagnosis of a physical disorder was more frequent if symptoms were on the right side rather than on the left (odds ratio (OR) = 7.7, 95% confidence interval (95% CI) 2.6-23), and in males than in females (OR = 3.0, 95% CI 1.1-8.3).


Preventive effect of theanine intake on stress-induced impairments of hippocamapal long-term potentiation and recognition memory.
Theanine, γ-glutamylethylamide, is one of the major amino acid components in green tea. On the basis of the preventive effect of theanine intake after birth on mild stress-induced attenuation of hippocamapal CA1 long-term potentiation (LTP), the present study evaluated the effect of theanine intake after weaning on stress-induced impairments of LTP and recognition memory. Young rats were fed water containing 0.3% theanine for 3 weeks after weaning and subjected to water immersion stress for 30min, which was more severe than tail suspension stress for 30s used previously. Serum corticosterone levels were lower in theanine-administered rats than in the control rats even after exposure to stress. CA1 LTP induced by a 100-Hz tetanus for 1s was inhibited in the presence of 2-amino-5-phosphonovalerate (APV), an N-methyl-d-aspartate (NMDA) receptor antagonist, in hippocampal slices from the control rats and was attenuated by water immersion stress. In contrast, CA1 LTP was not significantly inhibited in the presence of APV in hippocampal slices from theanine-administered rats and was not attenuated by the stress. Furthermore, object recognition memory was impaired in the control rats, but not in theanine-administered rats. The present study indicates the preventive effect of theanine intake after weaning on stress-induced impairments of hippocampal LTP and recognition memory. It is likely that the modification of corticosterone secretion after theanine intake is involved in the preventive effect.


Kinetics of RNA refolding in dynamic equilibrium by 1H-detected 15N exchange NMR spectroscopy.
By implementing new NMR methods that were designed to map very slow exchange processes we have investigated and characterized the refolding kinetics of a thermodynamically stable 34mer RNA sequence in dynamic equilibrium. The RNA sequence was designed to undergo a topologically favored conformational exchange between different hairpin folds, serving as a model to estimate the minimal time required for more complex RNA folding processes. Chemically prepared RNA sequences with sequence-selective (15)N labels provided the required signal separation and allowed a straightforward signal assignment of the imino protons by HNN correlation experiments. The 2D version of the new (1)H-detected (15)N exchange spectroscopy (EXSY) pulse sequence provided cross-peaks for resonances belonging to different folds that interchange on the time scale of longitudinal relaxation of (15)N nuclei bound to imino protons. The 34mer RNA sequence exhibits two folds which exchange on the observable time scale (tau(obs) approximately T(1){(15)Nu} < 5 s) and a third fold which is static on this time scale. A 1D version of the (15)N exchange experiment allowed the measurement of the exchange rates between the two exchanging folds as a function of temperature and the determination of the corresponding activation energies E(a) and frequency factors A. We found that the refolding rates are strongly affected by an entropically favorable preorientation of the replacing strand. The activation energies are comparable to values obtained for the slow refolding of RNA sequences of similar thermodynamic stability but less favorable topology.


Validation of a Smartphone App for the Assessment of Sedentary and Active Behaviors.
Although current technological advancements have allowed for objective measurements of sedentary behavior via accelerometers, these devices do not provide the contextual information needed to identify targets for behavioral interventions and generate public health guidelines to reduce sedentary behavior. Thus, self-reports still remain an important method of measurement for physical activity and sedentary behaviors. This study evaluated the reliability, validity, and sensitivity to change of a smartphone app in assessing sitting, light-intensity physical activity (LPA), and moderate-vigorous physical activity (MVPA). Adults (N=28; 49.0 years old, standard deviation [SD] 8.9; 85% men; 73% Caucasian; body mass index=35.0, SD 8.3 kg/m2) reported their sitting, LPA, and MVPA over an 11-week behavioral intervention. During three separate 7-day periods, participants wore the activPAL3c accelerometer/inclinometer as a criterion measure. Intraclass correlation (ICC; 95% CI) and bias estimates (mean difference [δ] and root of mean square error [RMSE]) were used to compare app-based reported behaviors to measured sitting time (lying/seated position), LPA (standing or stepping at <100 steps/minute), and MVPA (stepping at >100 steps/minute). Test-retest results suggested moderate agreement with the criterion for sedentary time, LPA, and MVPA (ICC=0.65 [0.43-0.82], 0.67 [0.44-0.83] and 0.69 [0.48-0.84], respectively). The agreement between the two measures was poor (ICC=0.05-0.40). The app underestimated sedentary time (δ=-45.9 [-67.6, -24.2] minutes/day, RMSE=201.6) and overestimated LPA and MVPA (δ=18.8 [-1.30 to 38.9] minutes/day, RMSE=183; and δ=29.3 [25.3 to 33.2] minutes/day, RMSE=71.6, respectively). The app underestimated change in time spent during LPA and MVPA but overestimated change in sedentary time. Both measures showed similar directions in changed scores on sedentary time and LPA. Despite its inaccuracy, the app may be useful as a self-monitoring tool in the context of a behavioral intervention. Future research may help to clarify reasons for under- or over-reporting of behaviors.


Exposure to internet pornography among children and adolescents: a national survey.
Estimates suggest that up to 90% or more youth between 12 and 18 years have access to the Internet. Concern has been raised that this increased accessibility may lead to a rise in pornography seeking among children and adolescents, with potentially serious ramifications for child and adolescent sexual development. Using data from the Youth Internet Safety Survey, a nationally representative, cross-sectional telephone survey of 1501 children and adolescents (ages 10-17 years), characteristics associated with self-reported pornography seeking behavior, both on the Internet and using traditional methods (e.g., magazines), are identified. Seekers of pornography, both online and offline, are significantly more likely to be male, with only 5% of self-identified seekers being female. The vast majority (87%) of youth who report looking for sexual images online are 14 years of age or older, when it is developmentally appropriate to be sexually curious. Children under the age of 14 who have intentionally looked at pornography are more likely to report traditional exposures, such as magazines or movies. Concerns about a large group of young children exposing themselves to pornography on the Internet may be overstated. Those who report intentional exposure to pornography, irrespective of source, are significantly more likely to cross-sectionally report delinquent behavior and substance use in the previous year. Further, online seekers versus offline seekers are more likely to report clinical features associated with depression and lower levels of emotional bonding with their caregiver. Results of the current investigation raise important questions for further inquiry. Findings from these cross-sectional data provide justification for longitudinal studies aimed at parsing out temporal sequencing of psychosocial experiences.


The immunomodulatory role of syncytiotrophoblast microvesicles.
Immune adaptation is a critical component of successful pregnancy. Of primary importance is the modification of cytokine production upon immune activation. With the discovery that normal pregnancy itself is a pro-inflammatory state, it was recognised that the classical Th1/Th2 cytokine paradigm, with a shift towards 'type 2' cytokine production (important for antibody production), and away from 'type 1' immunity (associated with cell mediated immunity and graft rejection), is too simplistic. It is now generally agreed that both arms of cytokine immunity are activated, but with a bias towards 'type 2' immunity. Many factors are released from the placenta that can influence the maternal cytokine balance. Here we focus on syncytiotrophoblast microvesicles (STBM) which are shed from the placenta into the maternal circulation. We show that STBM can bind to monocytes and B cells and induce cytokine release (TNFα, MIP-1α, IL-1α, IL-1β, IL-6, IL-8). Other cytokines are down-modulated, such as IP-10 which is associated with 'type 1' immunity. Therefore STBM may aid the 'type 2' skewed nature of normal pregnancy. We also observed that PBMC from third trimester normal pregnant women produce more TNFα and IL-6 in response to STBM than PBMC from non-pregnant women, confirming that maternal immune cells are primed by pregnancy, possibly through their interaction with STBM.


Receptor uptake arrays for vitamin B12, siderophores, and glycans shape bacterial communities.
Molecular variants of vitamin B12, siderophores, and glycans occur. To take up variant forms, bacteria may express an array of receptors. The gut microbe Bacteroides thetaiotaomicron has three different receptors to take up variants of vitamin B12 and 88 receptors to take up various glycans. The design of receptor arrays reflects key processes that shape cellular evolution. Competition may focus each species on a subset of the available nutrient diversity. Some gut bacteria can take up only a narrow range of carbohydrates, whereas species such as B. thetaiotaomicron can digest many different complex glycans. Comparison of different nutrients, habitats, and genomes provides opportunity to test hypotheses about the breadth of receptor arrays. Another important process concerns fluctuations in nutrient availability. Such fluctuations enhance the value of cellular sensors, which gain information about environmental availability and adjust receptor deployment. Bacteria often adjust receptor expression in response to fluctuations of particular carbohydrate food sources. Some species may adjust expression of uptake receptors for specific siderophores. How do cells use sensor information to control the response to fluctuations? This question about regulatory wiring relates to problems that arise in control theory and artificial intelligence. Control theory clarifies how to analyze environmental fluctuations in relation to the design of sensors and response systems. Recent advances in deep learning studies of artificial intelligence focus on the architecture of regulatory wiring and the ways in which complex control networks represent and classify environmental states. I emphasize the similar design problems that arise in cellular evolution, control theory, and artificial intelligence. I connect those broad conceptual aspects to many testable hypotheses for bacterial uptake of vitamin B12, siderophores, and glycans.


Percutaneous cystolithotomy in the pediatric augmented bladder.
Bladder stones are a common problem following augmentation cystoplasty. With the addition of Mitrofanoff channels for intermittent catheterization and more aggressive bladder neck tightening procedures, the incidence of stones has increased and endoscopic access to the bladder has become more complicated. We present our results of percutaneous endoscopic cystolithotomy in children with bladder augmentation. We performed percutaneous extraction of bladder calculi in 13 children with bladder augmentation. All patients performed catheterization either via a Mitrofanoff channel, artificial urinary sphincter or plicated ileal limb of an ileocecal reservoir. The prior suprapubic tube site was dilated with an Amplatz set for access, and stones were removed intact or fragmented by laser or electrohydraulic lithotripsy. Percutaneous extraction was successful in 12 of the 13 patients (92%). The remaining patient had a small posterior bladder perforation and open cystolithotomy was performed. All patients were discharged home in 24 to 36 hours, and there have been no stone recurrences with a mean followup of 24 months. Percutaneous stone removal using the previous suprapubic tract is a simple, effective and minimally invasive option for removing stones in an augmented bladder. This technique avoids potential injury to the continence mechanism of the reconstructed bladder neck or Mitrofanoff channel. Percutaneous stone removal has become our procedure of choice for managing calculi in the augmented bladder.


Brooding fathers, not siblings, take up nutrients from embryos.
It is well known that many animals with placenta-like structures provide their embryos with nutrients and oxygen. However, we demonstrate here that nutrients can pass the other way, from embryos to the parent. The study was done on a pipefish, Syngnathus typhle, in which males brood fertilized eggs in a brood pouch for several weeks. Earlier research has found a reduction of embryo numbers during the brooding period, but the fate of the nutrients from these 'reduced' embryos has been unknown. In this study, we considered whether (i) the brooding male absorbs the nutrients, (ii) siblings absorb them, or (iii) a combination of both. Males were mated to two sets of females, one of which had radioactively labelled eggs (using (14)C-labelled amino acids), such that approximately half the eggs in the brood pouch were labelled. This allowed us to trace nutrient uptake from these embryos. We detected that (14)C-labelled amino acids were transferred to the male brood pouch, liver and muscle tissue. However, we did not detect any significant (14)C-labelled amino-acid absorption by the non-labelled half-siblings in the brood pouch. Thus, we show, to our knowledge, for the first time, that males absorb nutrients derived from embryos through their paternal brood pouch.


Image segmentation and analysis via multiscale gradient watershed hierarchies.
Multiscale image analysis has been used successfully in a number of applications to classify image features according to their relative scales. As a consequence, much has been learned about the scale-space behavior of intensity extrema, edges, intensity ridges, and grey-level blobs. We investigate the multiscale behavior of gradient watershed regions. These regions are defined in terms of the gradient properties of the gradient magnitude of the original image. Boundaries of gradient watershed regions correspond to the edges of objects in an image. Multiscale analysis of intensity minima in the gradient magnitude image provides a mechanism for imposing a scale-based hierarchy on the watersheds associated with these minima. This hierarchy can be used to label watershed boundaries according to their scale. This provides valuable insight into the multiscale properties of edges in an image without following these curves through scale-space. In addition, the gradient watershed region hierarchy can be used for automatic or interactive image segmentation. By selecting subtrees of the region hierarchy, visually sensible objects in an image can be easily constructed.


The effect of simulated microgravity on bacteria from the Mir space station.
The effects of simulated microgravity on two bacterial isolates, Sphingobacterium thalpophilium and Ralstonia pickettii (formerly Burkholderia pickettii), originally recovered from water systems aboard the Mir space station were examined. These bacteria were inoculated into water, high and low concentrations of nutrient broth and subjected to simulated microgravity conditions. S. thalpophilium (which was motile and had flagella) showed no significant differences between simulated microgravity and the normal gravity control regardless of the method of enumeration and medium. In contrast, for R. pickettii (that was non-motile and lacked flagella), there were significantly higher numbers in high nutrient broth under simulated microgravity compared to normal gravity. Conversely, when R. pikkettii was inoculated into water (i.e., starvation conditions) significantly lower numbers were found under simulated microgravity compared to normal gravity. Responses to microgravity depended on the strain used (e.g., the motile strain exhibited no response to microgravity, while the non-motile strain did), the method of enumeration, and the nutrient concentration of the medium. Under oligotrophic conditions, non-motile cells may remain in geostationary orbit and deplete nutrients in their vicinity, while in high nutrient medium, resources surrounding the cell may be sufficient so that high growth is observed until nutrients becoming limiting.


Fatal fibrino-hemorrhagic bronchopneumonia associated with Morganella morganii in a bottlenose dolphin: a case report.
A 5 yr old, 184 kg, and 262 cm total length female bottlenose dolphin Tursiops truncatus was found dead in a display after bloody discharge from the blowhole was observed 3 h prior to death. Pathological examination revealed fibrinous bronchopneumonia with prominent areas of necrosis (sequestra) and numerous Gram-negative bacilli within alveoli and in blood vessels of the lungs and liver and between muscle fibers. The cause of death was attributed to septicemia. Often, cases of fibrinous bronchopneumonia are characterized by bacteremia in the latter stages of infection, resulting in the death of the animal. Septicemia likely accounts for the ecchymoses and petechiae noted on the spleen, pancreas, forestomach, lungs, visceral peritoneum, and small intestine. Additional lesions included hemothorax, stable red frothy fluid in the trachea, and lymphoid depletion in the spleen and lymph nodes. Pure growth of Morganella morganii was isolated from the lungs, blood, liver, and blowhole mucosa. Sequencing of 16s rRNA of the isolated bacteria showed more than 99.6% identity with M. morganii strain FDAARGOS_172. To our knowledge, this is the first report of fatal fibrinonecrotizing bronchopneumonia associated with M. morganii infection in a cetacean.


Microglia Mediate HIV-1 gp120-Induced Synaptic Degeneration in Spinal Pain Neural Circuits.
HIV-1 infection of the nervous system causes various neurological diseases, and synaptic degeneration is likely a critical step in the neuropathogenesis. Our prior studies revealed a significant decrease of synaptic protein, specifically in the spinal dorsal horn of patients with HIV-1 in whom pain developed, suggesting a potential contribution of synaptic degeneration to the pathogenesis of HIV-associated pain. However, the mechanism by which HIV-1 causes the spinal synaptic degeneration is unclear. Here, we identified a critical role of microglia in the synaptic degeneration. In primary cortical cultures (day in vitro 14) and spinal cords of 3- to 5-month-old mice (both sexes), microglial ablation inhibited gp120-induced synapse decrease. Fractalkine (FKN), a microglia activation chemokine specifically expressed in neurons, was upregulated by gp120, and knockout of the FKN receptor CX3CR1, which is predominantly expressed in microglia, protected synapses from gp120-induced toxicity. These results indicate that the neuron-to-microglia intercellular FKN/CX3CR1 signaling plays a role in gp120-induced synaptic degeneration. To elucidate the mechanism controlling this intercellular signaling, we tested the role of the Wnt/β-catenin pathway in regulating FKN expression. Inhibition of Wnt/β-catenin signaling blocked both gp120-induced FKN upregulation and synaptic degeneration, and gp120 stimulated Wnt/β-catenin-regulated FKN expression via NMDA receptors (NMDARs). Furthermore, NMDAR antagonist APV, Wnt/β-catenin signaling suppressor DKK1, or knockout of CX3CR1 alleviated gp120-induced mechanical allodynia in mice, suggesting a critical contribution of the Wnt/β-catenin/FKN/CX3R1 pathway to gp120-induced pain. These findings collectively suggest that HIV-1 gp120 induces synaptic degeneration in the spinal pain neural circuit by activating microglia via Wnt3a/β-catenin-regulated FKN expression in neurons.SIGNIFICANCE STATEMENT Synaptic degeneration develops in the spinal cord dorsal horn of HIV patients with chronic pain, but the patients without the pain disorder do not show this neuropathology, indicating a pathogenic contribution of the synaptic degeneration to the development of HIV-associated pain. However, the mechanism underlying the synaptic degeneration is unclear. We report here that HIV-1 gp120, a neurotoxic protein that is specifically associated with the manifestation of pain in HIV patients, induces synapse loss via microglia. Further studies elucidate that gp120 activates microglia by stimulating Wnt/β-catenin-regulated fractalkine in neuron. The results demonstrate a critical role of microglia in the pathogenesis of HIV-associated synaptic degeneration in the spinal pain neural circuit.


Influence of the mesenchymal cell source on oral epithelial development.
The extent of the influence of mesenchymal tissue on epithelial development is still debated, and elucidation of epithelial-mesenchymal interactions should be of relevance for controlling normal as well as pathological growth and development. The aim of the present study was to elucidate the influence of the mesenchymal cell type on oral mucosa epithelial development in vitro, using tissue-engineering principles, by including three different sources for mesenchymal cell type, viz. oral mucosa, skin and cornea, each of them presenting a distinct type of epithelium in situ. We investigated epithelial-mesenchymal interactions, considering both morphological criteria and protein expression (filaggrin, keratin 10, keratin 12, keratin 13 and laminin 5). The results of the histology, immunohistochemistry and transmission electron microscopy of the three types of tissue-engineered constructs composed of mesenchymal cells of different sources (oral, dermal and corneal fibroblasts) and of the same oral epithelial cells showed that the mesenchymal cell source had a significant influence on the thickness and ultrastructure of the epithelium, but not on the differentiation of oral epithelial cells, which might be an intrinsic property of these cells due to their genetic programming.


Synapse specificity of calcium release probed by chemical two-photon uncaging of inositol 1,4,5-trisphosphate.
Biological messengers can be "caged" by adding a single photosensitive group that can be photolyzed by a light flash to achieve spatially and temporally precise biochemical control. Here we report that photolysis of a double-caged form of the second messenger inositol 1,4,5-trisphosphate (IP3) triggers focal calcium release in Purkinje cell somata, dendrites, and spines as measured by two-photon microscopy. In calbindin knock-out Purkinje cells, peak calcium increased with flash energy with higher cooperativity for double-caged IP3 than for conventional single-caged IP3, consistent with a chemical two-photon effect. Spine photolysis of double-caged IP3 led to local calcium release. Uncaging of glycerophosphoryl-myo-inositol 4,5-bisphosphate (gPIP2), a poorly metabolizable IP3 analog, led to less well localized release. Thus, IP3 breakdown is necessary for spine-specificity. IP3- and gPIP2-evoked signals declined from peak with similar, slow time courses, indicating that release lasts hundreds of milliseconds and is terminated not by IP3 degradation but by intrinsic receptor dynamics. Based on measurements of spine-dendrite coupling, IP3-evoked calcium signals are expected to be at least 2.4-fold larger in their spine of origin than in nearby spines, allowing IP3 to act as a synapse-specific second messenger. Unexpectedly, single-caged IP3 led to less release in somata and was ineffective in dendrites and spines. Calcium release using caged gPIP2 was inhibited by the addition of single-caged IP3, suggesting that single-caged IP3 is an antagonist of calcium release. Caging at multiple sites may be an effective general approach to reducing residual receptor interaction.


Femtosecond time-delay X-ray holography.
Extremely intense and ultrafast X-ray pulses from free-electron lasers offer unique opportunities to study fundamental aspects of complex transient phenomena in materials. Ultrafast time-resolved methods usually require highly synchronized pulses to initiate a transition and then probe it after a precisely defined time delay. In the X-ray regime, these methods are challenging because they require complex optical systems and diagnostics. Here we propose and apply a simple holographic measurement scheme, inspired by Newton's 'dusty mirror' experiment, to monitor the X-ray-induced explosion of microscopic objects. The sample is placed near an X-ray mirror; after the pulse traverses the sample, triggering the reaction, it is reflected back onto the sample by the mirror to probe this reaction. The delay is encoded in the resulting diffraction pattern to an accuracy of one femtosecond, and the structural change is holographically recorded with high resolution. We apply the technique to monitor the dynamics of polystyrene spheres in intense free-electron-laser pulses, and observe an explosion occurring well after the initial pulse. Our results support the notion that X-ray flash imaging can be used to achieve high resolution, beyond radiation damage limits for biological samples. With upcoming ultrafast X-ray sources we will be able to explore the three-dimensional dynamics of materials at the timescale of atomic motion.


Determination of the dissociation constants for Ca2+ and calmodulin from the plasma membrane Ca2+ pump by a lipid probe that senses membrane domain changes.
The purpose of this work was to obtain information about conformational changes of the plasma membrane Ca(2+)-pump (PMCA) in the membrane region upon interaction with Ca(2+), calmodulin (CaM) and acidic phospholipids. To this end, we have quantified labeling of PMCA with the photoactivatable phosphatidylcholine analog [(125)I]TID-PC/16, measuring the shift of conformation E(2) to the auto-inhibited conformation E(1)I and to the activated E(1)A state, titrating the effect of Ca(2+) under different conditions. Using a similar approach, we also determined the CaM-PMCA dissociation constant. The results indicate that the PMCA possesses a high affinity site for Ca(2+) regardless of the presence or absence of activators. Modulation of pump activity is exerted through the C-terminal domain, which induces an apparent auto-inhibited conformation for Ca(2+) transport but does not modify the affinity for Ca(2+) at the transmembrane domain. The C-terminal domain is affected by CaM and CaM-like treatments driving the auto-inhibited conformation E(1)I to the activated E(1)A conformation and thus modulating the transport of Ca(2+). This is reflected in the different apparent constants for Ca(2+) in the absence of CaM (calculated by Ca(2+)-ATPase activity) that sharply contrast with the lack of variation of the affinity for the Ca(2+) site at equilibrium. This is the first time that equilibrium constants for the dissociation of Ca(2+) and CaM ligands from PMCA complexes are measured through the change of transmembrane conformations of the pump. The data further suggest that the transmembrane domain of the PMCA undergoes major rearrangements resulting in altered lipid accessibility upon Ca(2+) binding and activation.


hiPSC-Derived Schwann Cells Influence Myogenic Differentiation in Neuromuscular Cocultures.
Motoneurons, skeletal muscle fibers, and Schwann cells form synapses, termed neuromuscular junctions (NMJs). These control voluntary body movement and are affected in numerous neuromuscular diseases. Therefore, a variety of NMJ in vitro models have been explored to enable mechanistic and pharmacological studies. So far, selective integration of Schwann cells in these models has been hampered, due to technical limitations. Here we present robust protocols for derivation of Schwann cells from human induced pluripotent stem cells (hiPSC) and their coculture with hiPSC-derived motoneurons and C2C12 muscle cells. Upon differentiation with tuned BMP signaling, Schwann cells expressed marker proteins, S100b, Gap43, vimentin, and myelin protein zero. Furthermore, they displayed typical spindle-shaped morphologies with long processes, which often aligned with motoneuron axons. Inclusion of Schwann cells in coculture experiments with hiPSC-derived motoneurons and C2C12 myoblasts enhanced myotube growth and affected size and number of acetylcholine receptor plaques on myotubes. Altogether, these data argue for the availability of a consistent differentiation protocol for Schwann cells and their amenability for functional integration into neuromuscular in vitro models, fostering future studies of neuromuscular mechanisms and disease.


Gender and personal breastfeeding experience of rural GP registrars in Australia--a qualitative study of their effect on breastfeeding attitudes and knowledge.
While most doctors believe they have a major role to play in breastfeeding promotion, and consider it worthwhile taking time to assist women to continue to breastfeed, it appears that gender and personal breastfeeding experience affect their attitude and confidence concerning breastfeeding issues. As doctors practicing in rural and regional areas may be expected to provide a greater degree of assistance and support for breastfeeding women, their views on these topics are of particular interest. This article reports the results of qualitative interviews with eight GP registrars from rural and regional Australia, and their views about the influence gender and personal experience have on their ability to assist breastfeeding women. The study is part of a larger project investigating the breastfeeding skills and knowledge of GP registrars as a basis for designing a tailored educational breastfeeding resource. This project uses mixed methods and triangulation of data. Semi-structured, one-on-one interviews were conducted with eight GP registrars from southern Queensland, Australia. The participants were chosen so that there were eight unique combinations of age (<34 or > or =34), gender (male or female) and breastfeeding experience (self or spouse had breastfed/had not breastfed) to ensure diversity of responses and increase the transferability of results. Demographics were collected from each participant, as well as information about: their attitudes to breastfeeding and to counselling breastfeeding women; their perception of breastfeeding knowledge needs and their confidence assisting breastfeeding women; and prior training about breastfeeding. Transcripts of the recorded interviews were returned to the participants for verification before analysis. Emergent themes were identified both within and between interviews following content analysis. Four male and four female registrars with a mean age of 35 years (range 28-43 years) were recruited. Two participants of each gender were parents and their children had been breastfed for more than 6 months. Half the participants practised in small or other rural communities (RRMA 4 or 5), with three of the remainder practising in regional areas. Participants perceived that women thought female doctors were more knowledgeable and skilful concerning breastfeeding issues, regardless of their training or experience. They also assumed that women with breastfeeding problems would attend a female GP in preference to a male GP. These assumptions led male participants' to question the need for them to know any more than basic breastfeeding information. Being female, however, did not automatically confer special breastfeeding knowledge, with nulliparous female participants also mentioning a lack of knowledge and skills. In contrast, having personal breastfeeding experience (of self or spouse) was an important source of breastfeeding information and skill development, and increased the participants' confidence to assist breastfeeding women. Those without personal breastfeeding experience questioned the validity of the information they provided and felt that they would not be competent to assist mothers until they had had personal breastfeeding experience. This subset of rural Australian GP registrars acknowledged that both gender and personal experience with breastfeeding influenced their attitudes, perceived knowledge and confidence with breastfeeding issues. Female doctors were thought to be more knowledgeable and skilful in assisting breastfeeding women. Additionally, personal breastfeeding experience was thought to be important for gaining competence in the area. While GPs do not work with breastfeeding women in isolation, they appear to be an important resource for breastfeeding women, particularly when living in rural and remote areas. These results have implications for those training GP registrars. Both men and women should be encouraged to learn practical breastfeeding information and skills to assist breastfeeding women, rather than relying on personal or spousal breastfeeding experience. By having some expertise in the area, they can work in partnership with others in the community to provide the services mothers need.


Heterorhabditis gerrardi n. sp. (Nematoda: Heterorhabditidae): the hidden host of Photorhabdus asymbiotica (Enterobacteriaceae: gamma-Proteobacteria).
A new entomopathogenic nematode species from Australia, Heterorhabditis gerrardi n. sp. (Nematoda: Heterorhabditidae) is described. Morphological and molecular studies together with cross-hybridization tests indicated that this nematode represents a new undescribed species, closely related to members in the 'indica-group'. However, the new species can be distinguished from other species in this genus by a combination of several qualitative and quantitative morphological traits. Key diagnostic features include: body size and excretory pore position of the third-stage infective juveniles; male bursa with a reduction of bursal rays, usually affecting the terminal set of papillae, with symmetrical or asymmetrical loss of one or two pairs; vulva of hermaphrodites more anteriorly located than in other species in the indica-group (V% average: 43), with non-protruding or slightly protruding lips, and longer tail length (average: 106 mum). The new species can be further characterized by molecular traits of sequence data from the internal transcribed spacer (ITS) region of ribosomal DNA. Additionally, the bacterial symbiont of this new species, Photorhabdus asymbiotica Kingscliff strain, was phenotypically characterized and compared with other P. asymbiotica strains. The Kingscliff strain revealed many characters not present in other strains of this species. We hypothesize that the newly found traits may contribute to the maintenance of this mutualistic association of the bacterium with its nematode host.


Spatial conservation prioritization of biodiversity spanning the evolutionary continuum.
Accounting for evolutionary relationships between and within species is important for biodiversity conservation planning, but is rarely considered in practice. Here we introduce a novel framework to identify priority conservation areas accounting for phylogenetic and intraspecific diversity, integrating concepts from phylogeny, phylogeography, spatial statistics and spatial conservation prioritization. The framework allows planners to incorporate and combine different levels of evolutionary diversity and can be applied to any taxonomic group and to any region in the world. We illustrate our approach using amphibian and reptile species occurring in a biodiversity hotspot region, the Iberian Peninsula. We found that explicitly incorporating phylogenetic and intraspecific diversity in systematic conservation planning provides advantages in terms of maximizing overall biodiversity representation while enhancing its persistence and evolutionary potential. Our results emphasize the need to account for the evolutionary continuum in order to efficiently implement biodiversity conservation planning decisions.


Tumor angiogenesis as prognostic and predictive marker for chemotherapy dose-intensification efficacy in high-risk breast cancer patients within the WSG AM-01 trial.
The goal of this analysis was to characterize the survival impact of angiogenesis in the patients with high-risk breast cancer, particularly the predictive impact on benefit from dose intensification of adjuvant chemotherapy. Formalin-fixed tissue sample of 152 patients treated as part of the WSG AM-01 trial by either high-dose or conventional dose-dense chemotherapy were analyzed. Angiogenic activity was measured using microvessel count and vascular surface area (VSA) determined by the expression of vascular markers CD31 (n = 128) and CD105/endoglin (n = 130). Protein molecular breast cancer subclasses were analyzed by k-means clustering (k = 5). The univariate impact of factors on event-free (EFS) and overall survival (OS) was tested by log-rank statistics and quantified by univariate Cox analysis. Multivariate survival analysis included factors significant in univariate analysis, as well as interactions was performed for EFS. Both VSA/CD31 (P = 0.004) and VSA/CD105 (P = 0.003) were significantly higher among cases with increased Ki-67. A significant association with molecular subtypes was also found for VSA/CD105: in patients with basal-like/Her-2 subtypes, mean was 1.72 versus 1.24 in patients with other subtypes (P < 0.001). Elevated VSA/CD105 was associated with both significantly decreased EFS (P = 0.01) and OS (P = 0.02). Increased tumor size and positive Her-2 status were also prognostic for poorer EFS. The benefit of dose intensification for EFS was seen in those low-VSA/CD105 patients. The result was evident both in univariate and in multivariate survival analysis including all factors that were significant at the univariate level. Expression of angiogenesis markers may mirror or confer resistance to chemotherapy in the patients with breast cancer, particularly within the context of dose intensified chemotherapy. Highly angiogenic tumors may not derive sufficient benefit from dose intensification of chemotherapy alone. Our findings may serve as a rationale for further exploring anti-angiogenic treatment options in the patients with such highly angiogenic tumor subtypes.


NMR studies of the solution conformation of the sex peptide from Drosophila melanogaster.
The insect sex peptide (SP) elicits a variety of biological responses upon transfer to the mated female. SP contains 36 amino acids, including a tryptophan-rich N-terminal region, a central region containing five hydroxyproline (Hyp) residues, and a C-terminal region enclosed by a disulfide bridge. The solution structure of SP, studied here using NMR spectroscopy, includes a motif WPWN that adopts a type I β-turn in the N-terminal Trp-rich region. This turn region is connected to the central Hyp-rich region, which adopts extended and/or PPII-like conformations. The C-terminal disulfide-bonded loop populates helical turns or nascent helical structure. Overall, the results reveal a rather flexible peptide that lacks a compact folded structure in solution.


Use of Follicular Output Rate to Predict Intracytoplasmic Sperm Injection Outcome.
The measurement of follicular output rate (FORT) has been proposed as a good indicator for evaluating follicular response to the exogenous recombinant folliclestimulating hormone (rFSH). This places FORT as a promising qualitative marker for ovarian function. The objective of the study was to determine FORT as a predictor of oocyte competence, embryo quality and clinical pregnancy after intracytoplasmic sperm injection (ICSI). This prospective study was carried out on a group of infer- tile females (n=282) at Islamabad Clinic Serving Infertile Couples, Islamabad, Pakistan, from June 2010 till August 2013. Downregulated females were stimulated in injection gonadotropins and on ovulation induction day, pre-ovulatory follicle count (PFC) was determined using transvaginal ultrasound scan (TVUS), and FORT was determined as a ratio of PFC to antral follicle count (AFC)×100. Group I consisted of females with a negative pregnancy test, while group II had a positive pregnancy test that was confirmed with the appearance of fetal cardiac activity. Linear regression analyses of categorical variables of clinical pregnancy along with other independent variables, including FORT, were performed using SPSS version 15.0. Pregnancy occurred in 101/282 women who were tested, recording a clinical pregnancy rate of about 35.8%. FORT values were higher in group II as compared to group I females (P=0.0001). In multiple regression analysis, 97.7, 87.1, 78.2, and 83.4% variations were explained based on the number of retrieved oocytes per patients, number of metaphase II oocytes retrieved, number of fertilized oocytes, and number of cleaved embryos, respectively, indicating FORT as an independent predictor. FORT is a predictor of oocyte competence in terms of a number of retrieved, mature and fertilized oocytes. It also gives information about the number of cleaved embryos and clinical pregnancy rate.


Gene flow and population structure in the Mexican blind cavefish complex (Astyanax mexicanus).
Cave animals converge evolutionarily on a suite of troglomorphic traits, the best known of which are eyelessness and depigmentation. We studied 11 cave and 10 surface populations of Astyanax mexicanus in order to better understand the evolutionary origins of the cave forms, the basic genetic structuring of both cave and surface populations, and the degree to which present day migration among them affects their genetic divergence. To assess the genetic structure within populations and the relationships among them we genotyped individuals at 26 microsatellite loci. We found that surface populations are similar to one another, despite their relatively large geographic separation, whereas the cave populations are better differentiated. The cave populations we studied span the full range of the cave forms in three separate geographic regions and have at least five separate evolutionary origins. Cave populations had lower genetic diversity than surface populations, correlated with their smaller effective population sizes, probably the result of food and space limitations. Some of the cave populations receive migrants from the surface and exchange migrants with one another, especially when geographically close. This admixture results in significant heterozygote deficiencies at numerous loci due to Wahlund effects. Cave populations receiving migrants from the surface contain small numbers of individuals that are intermediate in both phenotype and genotype, affirming at least limited gene flow from the surface. Cave populations of this species are derived from two different surface stocks denoted "old" and "new." The old stock colonized caves at least three times independently while the new stock colonized caves at least twice independently. Thus, the similar cave phenotypes found in these caves are the result of repeated convergences. These phenotypic convergences have occurred in spite of gene flow from surface populations suggesting either strong natural or sexual selection for alleles responsible for the cave phenotype in the cave environment.


Why the elderly appear to be more severely affected by COVID-19: The potential role of immunosenescence and CMV.
The significantly higher mortality rates seen in the elderly compared with young children during the coronavirus disease 2019 (Covid-19) pandemic is likely to be driven in part by an impaired immune response in older individuals. Cytomegalovirus (CMV) seroprevalence approaches 80% in the elderly. CMV has been shown to accelerate immune ageing by affecting peripheral blood T cell phenotypes and increasing inflammatory mediated cytokines such as IL-6. The elderly with pre-existing but clinically silent CMV infection may therefore be particularly susceptible to severe Covid-19 disease and succumb to a cytokine storm which may have been promoted by CMV. Here, we evaluate the potential role of CMV in those with severe Covid-19 disease and consider how this relationship can be investigated in current research studies.


A comparison of self-reported analgesic use and detection of urinary ibuprofen and acetaminophen metabolites by means of metabonomics: the INTERMAP Study.
Information on dietary supplements, medications, and other xenobiotics in epidemiologic surveys is usually obtained from questionnaires and is subject to recall and reporting biases. The authors used metabolite data obtained from hydrogen-1 (or proton) nuclear magnetic resonance ((1)H NMR) analysis of human urine specimens from the International Study of Macro-/Micro-Nutrients and Blood Pressure (INTERMAP Study) to validate self-reported analgesic use. Metabolic profiling of two 24-hour urine specimens per individual was carried out for 4,630 participants aged 40-59 years from 17 population samples in Japan, China, the United Kingdom, and the United States (data collection, 1996-1999). (1)H NMR-detected acetaminophen and ibuprofen use was low (∼4%) among East Asian population samples and higher (>16%) in Western population samples. In a comparison of self-reported acetaminophen and ibuprofen use with (1)H NMR-detected acetaminophen and ibuprofen metabolites among 496 participants from Chicago, Illinois, and Belfast, Northern Ireland, the overall rate of concordance was 81%-84%; the rate of underreporting was 15%-17%; and the rate of underdetection was approximately 1%. Comparison of self-reported unspecified analgesic use with (1)H NMR-detected acetaminophen and ibuprofen metabolites among 2,660 Western INTERMAP participants revealed similar levels of concordance and underreporting. Screening for urinary metabolites of acetaminophen and ibuprofen improved the accuracy of exposure information. This approach has the potential to reduce recall bias and other biases in epidemiologic studies for a range of substances, including pharmaceuticals, dietary supplements, and foods.


Associations between gonadotropins, testosterone and β amyloid in men at risk of Alzheimer's disease.
Testosterone and gonadotropins have been associated with cognitive decline in men and the modulation of β amyloid (Aβ) metabolism. The relatively few studies that have investigated whether changes in one or a combination of these hormones influence Aβ levels have focused primarily on plasma Aβ(1-40) and not on the more pathogenic Aβ(1-42). Currently, no study has investigated whether these hormones are associated with an increase in brain amyloid deposition, ante mortem. Through the highly characterised Australian imaging, biomarkers and lifestyle study, we have determined the impact of these hormones on plasma Aβ levels and brain amyloid burden (Pittsburgh compound B (PiB) retention). Spearman's rank correlation and linear regression analysis was carried out across the cohort and within subclassifications. Luteinizing hormone (LH) was the only variable shown, in the total cohort, to have a significant impact on plasma Aβ(1-40) and Aβ(1-42) levels (beta=0.163, P<0.001; beta=0.446, P<0.001). This held in subjective memory complainers (SMC) (Aβ(1-40); beta=0.208, P=0.017; Aβ(1-42); beta=0.215, P=0.017) but was absent in mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups. In SMC, increased frequency of the APOE-ɛ4 allele (beta=0.536, P<0.001) and increasing serum LH levels (beta=0.421, P=0.004) had a significant impact on PiB retention. Whereas in MCI, PiB retention was associated with increased APOE-ɛ4 allele copy number (beta=0.674, P<0.001) and decreasing calculated free testosterone (beta=-0.303, P=0.043). These findings suggest a potential progressive involvement of LH and testosterone in the early preclinical stages of AD. Furthermore, these hormones should be considered while attempting to predict AD at these earliest stages of the disease.


Understanding the strategies rural cancer patients and survivors use to manage financial toxicity and the broader implications on their lives.
To explore strategies rural Australians use to cope with the financial consequences of their cancer diagnosis and how that impacts on their lives. Twenty adult cancer patients/survivors residing in regional-remote areas of Australia were purposively sampled and participated in audio-recorded, semi-structured interviews. When data saturation was reached, thematic analysis was employed to analyse the data. Participants were 20-78 years (M=60), 70% female, 35% were undergoing treatment and the remaining 65% had finished treatment within the past 5 years. Three themes provide context to rural financial toxicity-related experiences (travelling to access cancer treatment away from home is expensive, being single or lacking family support exacerbates the financial strain, and no choice other than to adopt cost-saving strategies if wanted to access treatment). Strategies commonly employed to minimise financial toxicity include: accessing travel-related support, changes to lifestyle (buying cheaper food, saving on utilities), accessing savings and retirement funds, missing holidays and social activities, reduced car use and not taking a companion to cancer-related appointments at metropolitan treatment areas. Although cost-saving strategies can effectively increase the ability of rural people to cover cancer treatment-related and other costs, most have broader negative psychological, social and practical consequences for them and their families. Increasing rural cancer patients' and survivors' awareness of various cost-saving strategies and their impact (positive and negative) may decrease their risk of experiencing financial toxicity and unexpected unintended consequences of adopting cost-saving measures.


Insufficient communication about medication use at the interface between hospital and primary care.
Lack of updated and uniform medication lists poses a problem for the continuity in patient care. The aim of this study was to estimate whether hospitals succeed in making accurate medication lists congruent with patients' actual medication use. Subsequently, the authors evaluated where errors were introduced and the possible implications of incongruent medication lists. Patients were visited within one week after discharge from surgical or medical department and interviewed about their use of prescription-only medication (POM). Stored drugs were inspected. Medication lists in hospital files and discharge letters were compared with the list obtained during the interview. The frequency of incorrect medication use and the potential consequences were estimated. A total of 83 surgical and 117 medical patients were included (n = 200), 139 patients (70%) were women. Median age was 75 years. Six patients stored no POM, 194 patients stored 1189 POM. Among the 955 currently-used POM, 749 POM (78%) were registered at some point during hospitalisation but only 444 (46%) were registered in discharge letters. 66 POM users had no medication list in their discharge letter. Local treatments (skin, eyes, airways) were registered less frequently than drugs administered orally. In total, 179 of the currently-used POM (19%) were not mentioned anywhere in hospital files, probably because of insufficient medication lists made at admission, and the prescribed regimen was unclear. At least 63 POM (7% of currently-used POM) were used in disagreement with the prescribed regimen. Approximately one fifth of used POM is unknown to the hospital and only half of used POM registered in discharge letters. Insufficient medication lists hamper clarifying whether or not patients use medication according to prescription. In order to prevent medication errors a systematic follow-up after discharge focusing on making an updated medication list might be needed.


Thermal adaptation of soil microbial respiration to elevated temperature.
In the short-term heterotrophic soil respiration is strongly and positively related to temperature. In the long-term, its response to temperature is uncertain. One reason for this is because in field experiments increases in respiration due to warming are relatively short-lived. The explanations proposed for this ephemeral response include depletion of fast-cycling, soil carbon pools and thermal adaptation of microbial respiration. Using a > 15 year soil warming experiment in a mid-latitude forest, we show that the apparent 'acclimation' of soil respiration at the ecosystem scale results from combined effects of reductions in soil carbon pools and microbial biomass, and thermal adaptation of microbial respiration. Mass-specific respiration rates were lower when seasonal temperatures were higher, suggesting that rate reductions under experimental warming likely occurred through temperature-induced changes in the microbial community. Our results imply that stimulatory effects of global temperature rise on soil respiration rates may be lower than currently predicted.


Phylogeny and systematics of Protodrilidae (Annelida) inferred with total evidence analyses.
Protodrilidae is a group of small, superficially simple-looking annelids, lacking chaetae and appendages, except for two prostomial palps. Originally considered to be one of the primitive "archiannelid" families, its affinity within Annelida is still highly debated. Protodrilids are found worldwide in the interstices of intertidal and subtidal marine sediments. Despite their simple appearance they constitute one of the most species-rich interstitial families, with 36 described species in two genera, Protodrilus and the gutless Astomus. Here we present the first phylogenetic study of Protodrilidae employing five gene fragments, 55 morphological characters and 73 terminals (including seven outgroups) analysed under direct optimization and parsimony as well as model-based methods. The large data set includes all 36 described species of Protodrilidae (17 of which are represented only by the morphological partition) as well as 30 undescribed or uncertain species (represented by both morphology and molecules). This comprehensive, inclusive and combined analysis revealed a new perspective on the phylogeny of Protodrilidae: the family is shown to contain six cosmopolitan subclades, each supported by several morphological apomorphies, and with the genus Astomus consistently nested among the other five clades rather than next to these. Consequently, the diagnosis of Protodrilus is emended, Astomus remains unchanged and the four remaining lineages are diagnosed and named Megadrilus n. gen, Meiodrilus gen. nov., Claudrilus n. gen and Lindrilus gen. nov. Character transformations showed that large size and presence of pigmentation, oviducts and eyes are plesiomorphies of the family, retained in Protodrilus, Megadrilus gen. nov. and Lindrilus gen. nov. These features are secondarily lost in the gutless Astomus with epidermal uptake of nutrients, as well as in Meiodrilus gen. nov. and some species of Claudrilus n. gen, with smaller size correlated to life in interstices of finer sediments.


Lacanobia oleracea nucleopolyhedrovirus (LaolNPV): A new European species of alphabaculovirus with a narrow host range.
During an insect sampling program in alfalfa crops near Montpellier, France in 2011, Lacanobia oleracea larvae were collected that died due to nucleopolyhedrovirus infection (LaolNPV). This virus was subjected to molecular and biological characterization. The virus was a multiple nucleocapsid NPV that showed similar restriction profiles to Mamestra configurata NPV-A (MacoNPV-A) but with significant differences. Polypeptide analysis demonstrated similar proteins in occlusion bodies and occlusion derived virions, to those observed in NPVs from Mamestra spp. Terminal sequencing revealed that the genome organization shared similarity with that of MacoNPV-A. The most homologous virus was MacoNPV-A 90/2 isolate (95.63% identity and 96.47% similarity), followed by MacoNPV-A 90/4 strain (95.37% and 96.26%), MacoNPV-B (89.21% and 93.53%) and M. brassicae MNPV (89.42% and 93.74%). Phylogenetic analysis performed with lef-8, lef-9, polh and a concatenated set of genes showed that LaolNPV and the Mamestra spp. NPVs clustered together with HaMNPV, but with a closer genetic distance to MacoNPV-A strains. The Kimura 2-parameter (K-2-P) distances of the complete genes were greater than 0.05 between LaolNPV and the MbMNPV/MacoNPV-B/HaMNPV complex, which indicates that LaolNPV is a distinct species. K-2-P distances were in the range 0.015-0.050 for comparisons of LaolNPV with MacoNPV-A strains, such that additional biological characteristics should be evaluated to determine species status. While MacoNPV-A was pathogenic to seven lepidopteran species tested, LaolNPV was only pathogenic to Chrysodeixis chalcites. Given these findings, Lacanobia oleracea nucleopolyhedrovirus should be considered as a new species in the Alphabaculovirus genus.


The structure of the S-layer of Clostridium difficile.
The nosocomially acquired pathogen Clostridium difficile is the primary causative agent of antibiotic associated diarrhoea and causes tens of thousands of deaths globally each year. C. difficile presents a paracrystalline protein array on the surface of the cell known as an S-layer. S-layers have been demonstrated to possess a wide range of important functions, which, combined with their inherent accessibility, makes them a promising drug target. The unusually complex S-layer of C. difficile is primarily comprised of the high- and low- molecular weight S-layer proteins, HMW SLP and LMW SLP, formed from the cleavage of the S-layer precursor protein, SlpA, but may also contain up to 28 SlpA paralogues. A model of how the S-layer functions as a whole is required if it is to be exploited in fighting the bacterium. Here, we provide a summary of what is known about the S-layer of C. difficile and each of the paralogues and, considering some of the domains present, suggest potential roles for them.


Political leaders and the media. Can we measure political leadership images in newspapers using computer-assisted content analysis?
Despite the large amount of research into both media coverage of politics as well as political leadership, surprisingly little research has been devoted to the ways political leaders are discussed in the media. This paper studies whether computer-aided content analysis can be applied in examining political leadership images in Dutch newspaper articles. It, firstly, provides a conceptualization of political leader character traits that integrates different perspectives in the literature. Moreover, this paper measures twelve political leadership images in media coverage, based on a large-scale computer-assisted content analysis of Dutch media coverage (including almost 150.000 newspaper articles), and systematically tests the quality of the employed measurement instrument by assessing the relationship between the images, the variance in the measurement, the over-time development of images for two party leaders and by comparing the computer results with manual coding. We conclude that the computerized content analysis provides a valid measurement for the leadership images in Dutch newspapers. Moreover, we find that the dimensions political craftsmanship, vigorousness, integrity, communicative performances and consistency are regularly applied in discussing party leaders, but that portrayal of party leaders in terms of responsiveness is almost completely absent in Dutch newspapers.


Sucking pressure and its relationship to milk transfer during breastfeeding in humans.
Breast sucking pressure has been only partially characterized in humans and its quantitative relationships with milk transfer and endocrine maternal responses are unknown. A method to record sucking pressure and milk transfer during complete sucking episodes is described. A tubing connected at one end to a pressure transducer was attached to the nipple so that the baby sucked both the nipple and the catheter during breastfeeding. The transducer's signals were fed into a commercial computer system designed to digitize and analyse physiological signals. A total of 27 recordings, 13 of which were from a single breast and 14 from both breasts were evaluated. Average values for the mean and maximum sucking pressures were -50 and -197 mmHg, respectively; the median intersuck interval was 0.7 s; and duration of the sucking episode was 7 min. Diverse sucking pressure patterns were observed due to different mixes of sucking bursts with steady sucking and stable versus decreasing pressure and frequency throughout each sucking episode. The amount of milk transferred to the baby was estimated from the difference in body weight immediately before and after each episode. Milk transfer from the second breast was 58% lower than from the first; this was associated with a significant decrease in grams of milk transferred per suck or per minute without significant changes in sucking pressure. The data suggest that there is a change in the maternal physiological response to sucking between the first and second breast. This report shows the feasibility of measuring the sucking pressure developed by human babies during complete nursing episodes, and offers great potential to explore the relationships between the physical parameters of sucking and maternal physiological responses, such as hormonal changes, milk yield and duration of lactational amenorrhoea.


In silico inquest reveals the efficacy of Cannabis in the treatment of post-Covid-19 related neurodegeneration.
Coronavirus (SARS-CoV-2), the causative agent of the Covid-19 pandemic has proved itself as the deadliest pathogen. A major portion of the population has become susceptible to this strain. Scientists are pushing their limits to formulate a vaccine against Covid-19 with the least side effects. Although the recent discoveries of vaccines have shown some relief from the covid infection rate, however, physical fatigue, mental abnormalities, inflammation and other multiple organ damages are arising as post-Covid symptoms. The long-term effects of these symptoms are massive. Patients with such symptoms are known as long-haulers and treatment strategy against this condition is still unknown. In this study, we tried to explore a strategy to deal with the post-Covid symptoms. We targeted three human proteins namely ACE2, Interleukin-6, Transmembrane serine protease and NRP1 which are already reported to be damaged via Covid-19 proteins and upregulated in the post-Covid stage. Our target plant in this study is Cannabis (popularly known as 'Ganja' in India). The molecular docking and simulation studies revealed that Cannabidiol (CBD) and Cannabivarin (CVN) obtained from Cannabis can bind to post-Covid symptoms related central nervous system (CNS) proteins and downregulate them which can be beneficial in post-covid symptoms treatment strategy. Thus we propose Cannabis as an important therapeutic plant against post-Covid symptoms.Communicated by Ramaswamy H. Sarma.


Reproductive arrest and stress resistance in winter-acclimated Drosophila suzukii.
Overwintering insects must survive the multiple-stress environment of winter, which includes low temperatures, reduced food and water availability, and cold-active pathogens. Many insects overwinter in diapause, a developmental arrest associated with high stress tolerance. Drosophila suzukii (Diptera: Drosophilidae), spotted wing drosophila, is an invasive agricultural pest worldwide. Its ability to overwinter and therefore establish in temperate regions could have severe implications for fruit crop industries. We demonstrate here that laboratory populations of Canadian D. suzukii larvae reared under short-day, low temperature, conditions develop into dark 'winter morph' adults similar to those reported globally from field captures, and observed by us in southern Ontario, Canada. These winter-acclimated adults have delayed reproductive maturity, enhanced cold tolerance, and can remain active at low temperatures, although they do not have the increased desiccation tolerance or survival of fungal pathogen challenges that might be expected from a more heavily melanised cuticle. Winter-acclimated female D. suzukii have underdeveloped ovaries and altered transcript levels of several genes associated with reproduction and stress. While superficially indicative of reproductive diapause, the delayed reproductive maturity of winter-acclimated D. suzukii appears to be temperature-dependent, not regulated by photoperiod, and is thus unlikely to be 'true' diapause. The traits of this 'winter morph', however, likely facilitate overwintering in southern Canada, and have probably contributed to the global success of this fly as an invasive species.


Toward resonator anharmonic sensors for precision crystal oscillators: a Gaussian model.
This paper addresses the statistical properties of eigenfrequency modes (anharmonics, for instance) of BAW crystal resonators in oscillators excited by noise or intended modulation and considered to be sensors of environmental impact. The modulated noisy model of a closed loop oscillator is studied for its amplitude-frequency and phase-frequency modulation characteristics caused by anharmonic influence. Pursuing the aim, we consider in detail amplitude, phase, and the time derivatives of an anharmonic sensor signal and present corresponding probability distributions for the different signal-to-noise ratios (SNR). Both statistical effects caused by noise and intended modulation are considered. Experimental results are also given.


Health risk assessment of volatile organic compounds exposure near Daegu dyeing industrial complex in South Korea.
Studying human health in areas with industrial contamination is a serious and complex issue. In recent years, attention has increasingly focused on the health implications of large industrial complexes. A variety of potential toxic chemicals have been produced during manufacturing processes and activities in industrial complexes in South Korea. A large number of dyeing industries gathered together in Daegu dyeing industrial complex. The residents near the industrial complex could be often exposed to volatile organic compounds. This study aimed to evaluate VOCs levels in the ambient air of DDIC, to assess the impact on human health risks, and to find more convincing evidences to prove these VOCs emitted from DDIC. According to deterministic risk assessment, inhalation was the most important route. Residential indoor, outdoor and personal exposure air VOCs were measured by passive samplers in exposed area and controlled area in different seasons. Satisfaction with ambient environments and self-reported diseases were also obtained by questionnaire survey. The VOCs concentrations in exposed area and controlled area was compared by t-test. The relationships among every VOC were tested by correlation. The values of hazard quotient (HQ) and life cancer risk were estimated. The concentrations of measured VOCs were presented, moreover, the variety of concentrations according the distances from the residential settings to the industrial complex site in exposed area. The residential indoor, outdoor, and personal exposure concentrations of toluene, DMF and chloroform in exposed area were significantly higher than the corresponding concentrations in controlled area both in summer and autumn. Toluene, DMF, chloroform and MEK had significantly positive correlations with each other in indoor and outdoor, and even in personal exposure. The HQ for DMF exceeded 1, and the life cancer risk of chloroform was greater than 10- 4 in exposed area. The prevalence of respiratory diseases, anaphylactic diseases and cardiovascular diseases in exposed area were significantly higher than in controlled area. This study showed that adverse cancer and non-cancer health effects may occur by VOCs emitted from DDIC, and some risk managements are needed. Moreover, this study provides a convenient preliminarily method for pollutants source characteristics.


Massive Pulmonary Embolism in a Patient Using Warfarin at Therapeutic Dose.
Warfarin sodium is commonly used for the prevention and treatment of thromboembolism. The efficacy of warfarin therapy depends on maintaining the International Normalised Ratio (INR) within the target range for the indication. A 56-year-old male presented to the emergency department with dyspnea and chest pain, together with pain and swelling in both legs. The patient had been taking warfarin at the therapeutic dose since having undergone an aortic valve replacement four years ago. His vital signs were an arterial pressure of 60/30 heart rate of 138 beats per minute, respiratory rate of 30 per minute and oxygen saturation of 60%. Computed tomography of the chest revealed thrombosis of the right pulmonary artery and its segmental branches. On investigating the aetiology of the venous thromboembolism, the level of Antithrombin III (AT III) activity was found to be at 37% (normal range, 80-120%).


Three-dimensional near-field MIMO array imaging using range migration techniques.
This paper presents a 3-D near-field imaging algorithm that is formulated for 2-D wideband multiple-input-multiple-output (MIMO) imaging array topology. The proposed MIMO range migration technique performs the image reconstruction procedure in the frequency-wavenumber domain. The algorithm is able to completely compensate the curvature of the wavefront in the near-field through a specifically defined interpolation process and provides extremely high computational efficiency by the application of the fast Fourier transform. The implementation aspects of the algorithm and the sampling criteria of a MIMO aperture are discussed. The image reconstruction performance and computational efficiency of the algorithm are demonstrated both with numerical simulations and measurements using 2-D MIMO arrays. Real-time 3-D near-field imaging can be achieved with a real-aperture array by applying the proposed MIMO range migration techniques.


ESPEN Guidelines on Parenteral Nutrition: intensive care.
Nutritional support in the intensive care setting represents a challenge but it is fortunate that its delivery and monitoring can be followed closely. Enteral feeding guidelines have shown the evidence in favor of early delivery and the efficacy of use of the gastrointestinal tract. Parenteral nutrition (PN) represents an alternative or additional approach when other routes are not succeeding (not necessarily having failed completely) or when it is not possible or would be unsafe to use other routes. The main goal of PN is to deliver a nutrient mixture closely related to requirements safely and to avoid complications. This nutritional approach has been a subject of debate over the past decades. PN carries the considerable risk of overfeeding which can be as deleterious as underfeeding. Therefore the authors will present not only the evidence available regarding the indications for PN, its implementation, the energy required, its possible complementary use with enteral nutrition, but also the relative importance of the macro- and micronutrients in the formula proposed for the critically ill patient. Data on long-term survival (expressed as 6 month survival) will also be considered a relevant outcome measure. Since there is a wide range of interpretations regarding the content of PN and great diversity in its practice, our guidance will necessarily reflect these different views. The papers available are very heterogeneous in quality and methodology (amount of calories, nutrients, proportion of nutrients, patients, etc.) and the different meta-analyses have not always taken this into account. Use of exclusive PN or complementary PN can lead to confusion, calorie targets are rarely achieved, and different nutrients continue to be used in different proportions. The present guidelines are the result of the analysis of the available literature, and acknowledging these limitations, our recommendations are intentionally largely expressed as expert opinions.