Electromagnetic wave scattering by highly elongated and geometrically composite objects of large size parameters: the generalized multipole technique.
The potency and versatility of a numerical procedure based on the generalized multipole technique (GMT) are demonstrated in the context of full-vector electromagnetic interactions for general incidence on arbitrarily shaped, geometrically composite, highly elongated, axisymmetric perfectly conducting or dielectric objects of large size parameters and arbitrary constitutive parameters. Representative computations that verify the accuracy of the technique are given for a large category of problems that have not been considered previously by the use of the GMT, to our knowledge. These problems involve spheroids of axial ratios as high as 20 and with the largest dimension of the dielectric object along the symmetry axis equal to 75 wavelengths; sphere-cone-sphere geometries; peanut-shaped scatterers; and finite-length cylinders with hemispherical, spherical, and flat end caps. Whenever possible, the extended boundary-condition method has been used in the process of examining the applicability of the suggested solution, with excellent agreement being achieved in all cases considered. It is believed that the numerical-scattering results presented here represent the largest detailed three-dimensional precise modeling ever verified as far as expansion functions that fulfill Maxwell's equations throughout the relevant domain of interest are concerned.


Comparative Network Reconstruction using mixed integer programming.
Signal-transduction networks are often aberrated in cancer cells, and new anti-cancer drugs that specifically target oncogenes involved in signaling show great clinical promise. However, the effectiveness of such targeted treatments is often hampered by innate or acquired resistance due to feedbacks, crosstalks or network adaptations in response to drug treatment. A quantitative understanding of these signaling networks and how they differ between cells with different oncogenic mutations or between sensitive and resistant cells can help in addressing this problem. Here, we present Comparative Network Reconstruction (CNR), a computational method to reconstruct signaling networks based on possibly incomplete perturbation data, and to identify which edges differ quantitatively between two or more signaling networks. Prior knowledge about network topology is not required but can straightforwardly be incorporated. We extensively tested our approach using simulated data and applied it to perturbation data from a BRAF mutant, PTPN11 KO cell line that developed resistance to BRAF inhibition. Comparing the reconstructed networks of sensitive and resistant cells suggests that the resistance mechanism involves re-establishing wild-type MAPK signaling, possibly through an alternative RAF-isoform. CNR is available as a python module at https://github.com/NKI-CCB/cnr. Additionally, code to reproduce all figures is available at https://github.com/NKI-CCB/CNR-analyses. Supplementary data are available at Bioinformatics online.


Empirical estimates of prostate cancer overdiagnosis by age and prostate-specific antigen.
Prostate cancer screening depends on a careful balance of benefits, in terms of reduced prostate cancer mortality, and harms, in terms of overdiagnosis and overtreatment. We aimed to estimate the effect on overdiagnosis of restricting prostate specific antigen (PSA) testing by age and baseline PSA. Estimates of the effects of age on overdiagnosis were based on population based incidence data from the US Surveillance, Epidemiology and End Results database. To investigate the relationship between PSA and overdiagnosis, we used two separate cohorts subject to PSA testing in clinical trials (n = 1,577 and n = 1,197) and a population-based cohort of Swedish men not subject to PSA-screening followed for 25 years (n = 1,162). If PSA testing had been restricted to younger men, the number of excess cases associated with the introduction of PSA in the US would have been reduced by 85%, 68% and 42% for age cut-offs of 60, 65 and 70, respectively. The risk that a man with screen-detected cancer at age 60 would not subsequently lead to prostate cancer morbidity or mortality decreased exponentially as PSA approached conventional biopsy thresholds. For PSAs below 1 ng/ml, the risk of a positive biopsy is 65 (95% CI 18.2, 72.9) times greater than subsequent prostate cancer mortality. Prostate cancer overdiagnosis has a strong relationship to age and PSA level. Restricting screening in men over 60 to those with PSA above median (>1 ng/ml) and screening men over 70 only in selected circumstances would importantly reduce overdiagnosis and change the ratio of benefits to harms of PSA-screening.


Predicting mortality in sick African children: the FEAST Paediatric Emergency Triage (PET) Score.
Mortality in paediatric emergency care units in Africa often occurs within the first 24 h of admission and remains high. Alongside effective triage systems, a practical clinical bedside risk score to identify those at greatest risk could contribute to reducing mortality. Data collected during the Fluid As Expansive Supportive Therapy (FEAST) trial, a multi-centre trial involving 3,170 severely ill African children, were analysed to identify clinical and laboratory prognostic factors for mortality. Multivariable Cox regression was used to build a model in this derivation dataset based on clinical parameters that could be quickly and easily assessed at the bedside. A score developed from the model coefficients was externally validated in two admissions datasets from Kilifi District Hospital, Kenya, and compared to published risk scores using Area Under the Receiver Operating Curve (AUROC) and Hosmer-Lemeshow tests. The Net Reclassification Index (NRI) was used to identify additional laboratory prognostic factors. A risk score using 8 clinical variables (temperature, heart rate, capillary refill time, conscious level, severe pallor, respiratory distress, lung crepitations, and weak pulse volume) was developed. The score ranged from 0-10 and had an AUROC of 0.82 (95 % CI, 0.77-0.87) in the FEAST trial derivation set. In the independent validation datasets, the score had an AUROC of 0.77 (95 % CI, 0.72-0.82) amongst admissions to a paediatric high dependency ward and 0.86 (95 % CI, 0.82-0.89) amongst general paediatric admissions. This discriminative ability was similar to, or better than other risk scores in the validation datasets. NRI identified lactate, blood urea nitrogen, and pH to be important prognostic laboratory variables that could add information to the clinical score. Eight clinical prognostic factors that could be rapidly assessed by healthcare staff for triage were combined to create the FEAST Paediatric Emergency Triage (PET) score and externally validated. The score discriminated those at highest risk of fatal outcome at the point of hospital admission and compared well to other published risk scores. Further laboratory tests were also identified as prognostic factors which could be added if resources were available or as indices of severity for comparison between centres in future research studies.


Breastfeeding in England: time trends 2005-2006 to 2012-2013 and inequalities by area profile.
Breastfeeding rates in England have risen steadily since the 1970s, but rates remain low and little is known about area-based trends. We report an ecological analysis of time trends in area breastfeeding rates in England using annual data on breastfeeding initiation (2005-2006 to 2012-2013) and any breastfeeding at 6-8 weeks (2008-2009 to 2012-2013) for 151 primary care trusts (PCTs). Overall, breastfeeding initiation rose from 65.5% in 2005-2006 to 72.4% in 2012-2013 (average annual absolute increase 0.9%). There was a statistically significantly higher (interaction P < 0.001) annual increase in initiation in PCTs in the most deprived (1.2%) compared with the least deprived tertile (0.7%), and in PCTs with low baseline breastfeeding initiation (2005-2006; 1.4%) compared with high baseline initiation (0.6%). Similar trends were observed when PCTs were stratified by the proportion of teenage mothers and maternal smoking, but not when stratified by ethnicity. Although breastfeeding prevalence at 6-8 weeks also increased significantly over the observed time period (41.2% in 2008-2009, 43.7% in 2012-2013; annual increase 0.7%), there was no difference in the average increase by deprivation profile, ethnicity, teenage mothers and maternal smoking. However, PCTs with low baseline prevalence in 2008-2009 saw a significantly larger annual increase (0.8%) compared with PCTs with high baseline prevalence (0.07%). In conclusion, breastfeeding initiation and prevalence have seen higher increases in areas with low initial breastfeeding, and for initiation, more disadvantaged areas. Although these results suggest that inequalities in breastfeeding have narrowed, rates have plateaued since 2010-2011. Sustained efforts are needed to address breastfeeding inequalities.


[Comparison of cerclage and cerclage pessary in the treatment of pregnant women with incompetent cervix and threatened preterm delivery].
Cervical incompetence is one of the causes of preterm delivery. Ultrasound examination of the cervix has given the evidence that cervical shortening, dilatation of internal cervical os and funneling observed long before term are the warning signs of preterm delivery. Early diagnosis and treatment may serve better outcome. Cerclage, which has been employed for more than 50 years is a traumatic procedure, furthermore requiring anaesthesia. Cerclage pessary can be a safe alternative to cerclage. This method seems to be less invasive. The aim of the study was to compare the effectiveness of the two methods employed in gravid patients between 22 and 27 completed weeks of pregnancy with clinically and ultrasonographically confirmed shortening of the cervix. We analysed 57 patients, 22 treated with McDonald cerclage procedure and 35 with pessary. The primary outcome measure was prolongation of pregnancy--mean 13.4 weeks and 12.1 weeks for cerclage and pessary respectively (p = 0.06). There were no significant differences regarding the mode of delivery, rate of prematurity, mean birthweight and Apgar score. Cerclage and cerclage pessary are equally effective methods of prolongation of pregnancy in gravid patients with incompetent cervix and threatened preterm labor. The choice of the method does not affect the mode of delivery as well as neonatal outcome.


Detecting Distress: Introducing Routine Screening in a Gynecologic Cancer Setting.
Cancer results in a wide range of challenges that contribute to patient distress. Detecting distress in patients can result in improved patient outcomes, and early intervention can avoid patients having unmet needs. The aims were to determine the prevalence of distress in patients with gynecologic cancers, identify specific problems, and explore staff perceptions of distress screening. A mixed-methods design was used. Quantitative data were collected on distress levels and problems. Qualitative interviews were conducted with healthcare professionals. Sixty-six percent of women scored 4 or greater on the Distress Thermometer, which was used as the indicator for follow-up or referral. A third reported low distress, and the same proportion was highly distressed. The top five problems identified by participants were nervousness, worry, fears, fatigue, and sleep problems.


Release and establishment of the parasitoid Diachasmimorpha kraussii against the tephritid fruit fly Bactrocera latifrons in Hawaii.
Diachasmimorpha kraussii (Fullaway) (Hymenoptera: Braconidae) was first released against Bactrocera latifrons (Hendel) (Diptera: Tephritidae) in Hawaii in March 2003. Over a three month period, eight releases, totaling 7,696 females and 3,968 males, were made in a turkeyberry, Solanum torvum Swartz (Solanales: Solanaceae) patch known to have a well established B. latifrons population. The establishment of D. kraussii was assessed through fruit collections conducted over a three-year period beyond the last release. D. kraussii was recovered 2 weeks, 31 months, and 39 months after the last parasitoid release, with collections not only from the release site, but also from a control site about 5.0 km distance from the release site. Recovery from fruit collections three years after the last parasitoid release confirmed that D. kraussii had become established in Hawaii. Parasitism rates were low, only 1.0-1.4%, compared to rates of 2.8-8.7% for the earlier established egg-larval parasitoid, Fopius arisanus (Sonan).


Identification and characterization of the autophagy-related genes Atg12 and Atg5 in hydra.
Autophagy is an evolutionarily conserved process in eukaryotic cells that is involved in the degradation of cytoplasmic contents including organelles via the lysosome. Hydra is an early metazoan which exhibits simple tissue grade organization, a primitive nervous system, and is one of the classical non-bilaterian models extensively used in evo-devo research. Here, we describe the characterization of two core autophagy genes, Atg12 and Atg5, from hydra. In silico analyses including sequence similarity, domain analysis, and phylogenetic analysis demonstrate the conservation of these genes across eukaryotes. The predicted 3D structure of hydra Atg12 showed very little variance when compared to human Atg12 and yeast Atg12, whereas the hydra Atg5 predicted 3D structure was found to be variable, when compared with its human and yeast homologs. Strikingly, whole mount in situ hybridization showed high expression of Atg12 transcripts specifically in nematoblasts, whereas Atg5 transcripts were found to be expressed strongly in budding region and growing buds. This study may provide a framework to understand the evolution of autophagy networks in higher eukaryotes.


Can resistant starch and/or aspirin prevent the development of colonic neoplasia? The Concerted Action Polyp Prevention (CAPP) 1 Study.
Loss of function of the adenomatous polyposis coli (APC) tumour suppressor gene through truncating mutations or other means is an early event in most colo-rectal cancer (CRC). The APC gene encodes a large multifunctional protein that plays key roles in several cellular processes, including the wnt signalling pathway where an intact APC protein is essential for down regulation of beta-catenin. The APC protein also plays a role in regulation of cell proliferation, differentiation, apoptosis, cell-cell adhesion, cell migration and chromosomal stability during mitosis. Acquisition of a non-functional APC gene can occur by inheritance (in the disease familial adenomatous polyposis (FAP)) or by a sporadic event in a somatic cell. Whilst there is strong epidemiological evidence that variation in diet is a major determinant of variation in CRC incidence, conventional adenoma recurrence trials in sporadic cases of the disease have been relatively unsuccessful in identifying potentially protective food components. Since the genetic basis of CRC in FAP and in sporadic CRC is similar, intervention trials in FAP gene carriers provide an attractive strategy for investigation of potential chemo-preventive agents, since smaller numbers of subjects and shorter time frames are needed. The Concerted Action Polyp Prevention (CAPP) 1 Study is using a 2 x 2 factorial design to test the efficacy of resistant starch (30 g raw potato starch-Hylon VII (1:1, w/w)/d) and aspirin (600 mg/d) in suppressing colo-rectal adenoma formation in young subjects with FAP. Biopsies of macroscopically-normal rectal mucosa are also being collected for assay of putative biomarkers of CRC risk.


Influence of HAART on HIV-related CNS disease and neuroinflammation.
Neuroinflammation has an established link with AIDS-related dementia but has not been investigated in the post-highly active anti-retroviral therapy (HAART) era. In this autopsy study we examined post-HAART cases in Edinburgh for the presence of HIV-related pathology and in well-treated cases for evidence of neuroinflammation. We focused on basal ganglia and the hippocampus, 2 key areas of the brain for cognitive functioning and compared pre- and post-HAART cases for neuroinflammatory status. We find evidence, post-HAART, that there is a high level of microglial/macrophage activation that is comparable with the levels seen, pre-HAART, in HIV encephalitis (HIVE) and AIDS cases. This result was maximal in the hippocampus where microglial/macrophage upregulation in the HAART-treated group exceeded that seen in HIVE. In the basal ganglia, HAART-treated cases showed significantly higher levels of CD68-positive microglia/macrophages than in control brains (p = 0.004), and in the hippocampus levels were significantly higher than those seen in control cases, pre-HAART AIDS, and presymptomatic brains (p = 0.01). However, lymphocyte levels in the areas examined were low in HAART-treated cases. We conclude that there is a surprising degree of ongoing neuroinflammation in HAART-treated patients, particularly in the hippocampus. This may pose a threat for the future health of individuals maintained long-term on HAART therapy.


Is the job satisfaction of primary care team members associated with patient satisfaction?
BACKGROUND Previous research has shown a correlation between physician job satisfaction and patient satisfaction with quality of care, but the connection between job satisfaction of other primary care team members and patient satisfaction is yet unclear. OBJECTIVE To evaluate whether there is an association between patient satisfaction and job satisfaction of the members of patient care teams. DESIGN The study was based on data from the European Practice Assessment and used an observational design. SETTING 676 primary care practices in Germany. PARTICIPANTS 47 168 patients, 676 general practitioners (practice principals), 305 physician colleagues (trainees and permanently employed physicians) and 3011 non-physician practice members (nurses, secretaries). MAIN OUTCOME MEASURES Patient evaluation was measured using the 23-item EUROPEP questionnaire. Job satisfaction was measured using the 10-item Warr-Cook-Wall job satisfaction scale and further items relating to practice structure. Bivariate correlations were applied in which factors of patient satisfaction and practice structure were compared with physicians and non-physicians satisfaction. RESULTS Patient satisfaction correlates positively with the general job satisfaction of the non-physician (r=0.25, p<0.01) and no significant correlation was found for the general job satisfaction of practice principals and physician colleagues. Patients' satisfaction with the practice organisation correlates positively with the general job satisfaction of the non-physicians (r=0.30, p<0.01) and their view of practice structure (r=0.29, p<0.01). CONCLUSIONS The correlation between non-physician team member satisfaction and patient satisfaction was higher than the correlation between satisfaction of physicians and patients. Patients seem to be sensitive to aspects of practice structure.


Outcomes of Acute Kidney Injury in Patients With Severe ARDS Due to Influenza A(H1N1) pdm09 Virus.
The incidence and long-term outcomes of acute kidney injury in patients with severe acute respiratory distress syndrome (ARDS) due to influenza A(H1N1) pdm09 virus (pH1N1) have not been examined. To assess long-term renal recovery in patients with acute kidney injury and severe ARDS due to pH1N1. A retrospective observational cohort study of adults with severe pH1N1-associated ARDS admitted to a tertiary referral center. Baseline characteristics, acute kidney injury stage, continuous renal replacement therapy (CRRT), intermittent hemodialysis, extracorporeal membrane oxygenation, survival, and renal recovery (defined as dialysis independence) were evaluated. Fifty-seven patients, most with stage 3 acute kidney injury, were included. The 53% mortality rate among the 38 patients requiring CRRT was significantly higher than the 0% mortality rate among the 19 patients not requiring CRRT or intermittent hemodialysis. Increased duration of CRRT was not significantly associated with decreased survival. Fifteen CRRT patients required transition to intermittent hemodialysis. Of the CRRT patients who survived, 94% experienced renal recovery. Extracorporeal membrane oxygenation was instituted in 17 patients; 15 of these patients required CRRT. Acute kidney injury is common in patients with severe ARDS caused by pH1N1 infection. CRRT is a significant risk factor for increased mortality, but most patients who survived experienced full renal recovery.


Physical and Mental Functioning in Patients with Established Rheumatoid Arthritis over an 11-year Followup Period: The Role of Specific Comorbidities.
To investigate the longterm association of a wide range of comorbidities with physical and mental functioning in patients with rheumatoid arthritis (RA). Longitudinal data over a period of 11 years were collected from 882 patients with RA. Somatic comorbidity and comorbid depression were measured at baseline, with a questionnaire including 20 chronic diseases and with the Center for Epidemiologic Depression Scale, respectively. Physical functioning was measured at 5 timepoints with a disease-specific measure [Health Assessment Questionnaire (HAQ)] and a generic measure [physical scales of the Medical Outcomes Study Short Form-36 (SF-36)]. Mental functioning was measured with the mental scales of the SF-36. To determine the association of baseline-specific comorbidities with functioning over time, we performed longitudinal analyses. At baseline, 72% percent of the patients were women, mean age ± SD was 59.3 ± 14.8 years, median RA disease duration was 5.0 years, and 68% had ≥ 1 comorbid condition. The effect of comorbid conditions was more apparent when physical functioning was measured with SF-36, a disease-generic measure, compared with the HAQ, a disease-specific measure. Circulatory conditions and depression were associated (p < 0.05) with worse physical functioning according to the HAQ. Respiratory conditions, musculoskeletal conditions, cancer, and depression were associated (p < 0.05) with worse physical functioning according to the SF-36. Respiratory conditions and depression were associated with worse mental functioning. Patients with specific comorbid conditions have an increased risk of low functioning in the long term. Targeted attention for these specific comorbid conditions by clinicians is recommended.


Estimating Photosynthetic Attributes from High-Throughput Canopy Hyperspectral Sensing in Sorghum.
Sorghum, a genetically diverse C4 cereal, is an ideal model to study natural variation in photosynthetic capacity. Specific leaf nitrogen (SLN) and leaf mass per leaf area (LMA), as well as, maximal rates of Rubisco carboxylation (V cmax), phosphoenolpyruvate (PEP) carboxylation (V pmax), and electron transport (J max), quantified using a C4 photosynthesis model, were evaluated in two field-grown training sets (n = 169 plots including 124 genotypes) in 2019 and 2020. Partial least square regression (PLSR) was used to predict V cmax (R 2 = 0.83), V pmax (R 2 = 0.93), J max (R 2 = 0.76), SLN (R 2 = 0.82), and LMA (R 2 = 0.68) from tractor-based hyperspectral sensing. Further assessments of the capability of the PLSR models for V cmax, V pmax, J max, SLN, and LMA were conducted by extrapolating these models to two trials of genome-wide association studies adjacent to the training sets in 2019 (n = 875 plots including 650 genotypes) and 2020 (n = 912 plots with 634 genotypes). The predicted traits showed medium to high heritability and genome-wide association studies using the predicted values identified four QTL for V cmax and two QTL for J max. Candidate genes within 200 kb of the V cmax QTL were involved in nitrogen storage, which is closely associated with Rubisco, while not directly associated with Rubisco activity per se. J max QTL was enriched for candidate genes involved in electron transport. These outcomes suggest the methods here are of great promise to effectively screen large germplasm collections for enhanced photosynthetic capacity.


Contrasting Patterns of Serologic and Functional Antibody Dynamics to Plasmodium falciparum Antigens in a Kenyan Birth Cohort.
IgG antibodies to Plasmodium falciparum are transferred from the maternal to fetal circulation during pregnancy, wane after birth, and are subsequently acquired in response to natural infection. We examined the dynamics of malaria antibody responses of 84 Kenyan infants from birth to 36 months of age by (i) serology, (ii) variant surface antigen (VSA) assay, (iii) growth inhibitory activity (GIA), and (iv) invasion inhibition assays (IIA) specific for merozoite surface protein 1 (MSP1) and sialic acid-dependent invasion pathway. Maternal antibodies in each of these four categories were detected in cord blood and decreased to their lowest level by approximately 6 months of age. Serologic antibodies to 3 preerythrocytic and 10 blood-stage antigens subsequently increased, reaching peak prevalence by 36 months. In contrast, antibodies measured by VSA, GIA, and IIA remained low even up to 36 months. Infants sensitized to P. falciparum in utero, defined by cord blood lymphocyte recall responses to malaria antigens, acquired antimalarial antibodies at the same rate as those who were not sensitized in utero, indicating that fetal exposure to malaria antigens did not affect subsequent infant antimalarial responses. Infants with detectable serologic antibodies at 12 months of age had an increased risk of P. falciparum infection during the subsequent 24 months. We conclude that serologic measures of antimalarial antibodies in children 36 months of age or younger represent biomarkers of malaria exposure rather than protection and that functional antibodies develop after 36 months of age in this population.


Selective publication of antidepressant trials and its influence on apparent efficacy: Updated comparisons and meta-analyses of newer versus older trials.
Valid assessment of drug efficacy and safety requires an evidence base free of reporting bias. Using trial reports in Food and Drug Administration (FDA) drug approval packages as a gold standard, we previously found that the published literature inflated the apparent efficacy of antidepressant drugs. The objective of the current study was to determine whether this has improved with recently approved drugs. Using medical and statistical reviews in FDA drug approval packages, we identified 30 Phase II/III double-blind placebo-controlled acute monotherapy trials, involving 13,747 patients, of desvenlafaxine, vilazodone, levomilnacipran, and vortioxetine; we then identified corresponding published reports. We compared the data from this newer cohort of antidepressants (approved February 2008 to September 2013) with the previously published dataset on 74 trials of 12 older antidepressants (approved December 1987 to August 2002). Using logistic regression, we examined the effects of trial outcome and trial cohort (newer versus older) on transparent reporting (whether published and FDA conclusions agreed). Among newer antidepressants, transparent publication occurred more with positive (15/15 = 100%) than negative (7/15 = 47%) trials (OR 35.1, CI95% 1.8 to 693). Controlling for trial outcome, transparent publication occurred more with newer than older trials (OR 6.6, CI95% 1.6 to 26.4). Within negative trials, transparent reporting increased from 11% to 47%. We also conducted and contrasted FDA- and journal-based meta-analyses. For newer antidepressants, FDA-based effect size (ESFDA) was 0.24 (CI95% 0.18 to 0.30), while journal-based effect size (ESJournals) was 0.29 (CI95% 0.23 to 0.36). Thus, effect size inflation, presumably due to reporting bias, was 0.05, less than for older antidepressants (0.10). Limitations of this study include a small number of trials and drugs-belonging to a single class-and a focus on efficacy (versus safety). Reporting bias persists but appears to have diminished for newer, compared to older, antidepressants. Continued efforts are needed to further improve transparency in the scientific literature.


Retinal microvascular patency in the diabetic rat.
To study whether the patency to erythrocytes in retinal microvessels of diabetic rats is reduced or blocked before the vessels lose their patency to plasma flow. We used recognized techniques to induce diabetic and galactose related microvascular retinal lesions in rats: (1) alloxan induction (2) streptozotocin induction (3) galactose-containing diet. The rats were followed up to 17 months. We used our vascular trichrome technique to observe the effects of the ongoing diabetes on the retinal microcirculation. A focal leakage of a plasma-borne fluorescent dye was noted around the junction of the deep retinal capillaries and the ascending venules to the superficial retinal circulation in the streptozotocin and alloxan diabetic rats by the 14th month, and, by the 16th month, retinal capillary non-perfusion and retinal vascular malformations were present. The affected vessels showed patency to microspheres (0.2 microm in diameter) but no perfusion of erythrocytes. No such changes were seen in the galactose-fed rats. (1) The location between the deep retinal capillary net and the ascending venules may be the site of early vascular leakage in the diabetic rat model, (2) the erythrocytes' passage in the affected retinal microcirculation was blocked before the development of complete blockage to plasma in diabetic rats. The logical assumption that during the development stage of retinal capillary occlusion there may be a transient stage of microvascular insufficiency was examined. The lathyrogen, imino-diproprionitrile (IDPN), had previously been effective for creating a fast-developing model of retinal vasculopathy. Using that model, we demonstrated a stage in which the retinal microvasculature was blocked to erythrocytes but not to plasma [1]. However, we questioned the applicability of our findings to more slowly developing microvasculopathies, such as diabetic retinopathy. We designed the current study to examine the presence of such stage in slowly developing microvasculopathy. Animal models that are known to induce "diabetic retinopathy-like" changes used [2-4]. The diabetic animals were followed for a period of 17 months. Starting at the 12th month, a few animals of each group were killed and the retains were examined with our trichrome method [1] for relative capillary patency to erythrocytes and plasma, for functionality of endothelial cells, and for disturbances in the blood-retinal barrier. The results of this study support the hypothesis that retinal microvascular insufficiency does exist as a temporary stage that precedes the development of complete capillary blockage in long-term developing rat models of diabetic retinopathy.


Management of Gigantomastia: Outcomes of Superomedial Pedicle with Vertical Scar or Wise Pattern Skin Excision.
Gigantomastia is a rare condition characterized by excessive breast growth and can be physically and psychosocially disabling for the patient. Regarding management of gigantomastia, this study evaluates the outcomes of superomedial pedicle with vertical scar or wise pattern skin excision. A total of 425 patients who underwent reduction mammoplasty in our institution were reviewed. Forty eight reduction mammoplasty patients with resection weights greater than 1 kg per breast and treated with superomedial dermoglandular pedicle technique combined with vertical or wise-pattern skin excision were included. The patients were between 19 and 66 years old, with an average of 41 years. Total weight of resection was between 1000 and 2600 g, with an average of 1384 grams for right breast and between 1000 and 3000g, with an average of 1434 grams for left breast. The secondary revisions and wound healing complications were extremely high in vertical scar group compared to wise pattern group (87,5% and 12,5%, respectively). The authors concluded that superomedial dermoglandular pedicle in the addition of a wise pattern is an appropriate, safe and reliable method when dealing with significantly larger breasts (>1000g).


Is there an "unhealthy volunteer effect" in mental health outpatient research?
The ability to generalize clinical research findings depends on whether patients who agree to participate in studies have more or less severe illness than applicable clinical populations. We analyzed data from standardized clinical interviews given to patients seeking outpatient mental health treatment to determine whether there were differences between those who were willing to consider research participation and those who were not. Univariate and multivariable logistic regression analyses were conducted using measures of demographics, symptom and illness severity, and social environment. Factors associated with increased likelihood of willingness to consider research participation in the multivariable analysis were: moderate to severe depressive symptoms (OR=1.26; 95%CI: 1.07,1.48), hazardous drinking (OR=1.44, 95%CI: 1.19,1.75), having 1-15 days of partial disability due to mental illness (OR=1.19, 95%CI: 1.00,1.42), having any mental health outpatient visits in the last 2 years (OR=1.24; 95%CI: 1.09,1.42), and having a family member with mental illness (OR=1.57, 95%CI: 1.37,1.79). These results suggest an "unhealthy volunteer effect"-that patients interested in volunteering for outpatient mental health research have more severe illness, longer treatment history, and possibly greater genetic loading for mental illness than those not included in research trials. The possibility of such an effect should be considered when conducting and interpreting clinical trials.


How animals collaborate: Underlying proximate mechanisms.
Collaboration or social interactions in which two or more individuals coordinate their behavior to produce outcomes from which both individuals benefit are common in nature. Individuals from many species hunt together, defend their territory, and form coalitions in intragroup competition. However, we still know very little about the proximate mechanisms underlying these behaviors. Recent theories of human cognitive evolution have emphasized the role collaboration may have played in the selection of socio-cognitive skills. It has been argued that the capacity to form shared goals and joint intentions with others, is what allows humans to collaborate so flexibly and efficiently. Although there is no evidence that nonhuman animals are capable of shared intentionality, there is conceivably a wide range of proximate mechanisms that support forms of, potentially flexible, collaboration in other species. We review the experimental literature with the aim of evaluating what we know about how other species achieve collaboration; with a particular focus on chimpanzees. We structure the review with a new categorization of collaborative behavior that focuses on whether individuals intentionally coordinate actions with others. We conclude that for a wider comparative perspective we need more data from other species but the findings so far suggest that chimpanzees, and possibly other great apes, are capable of understanding the causal role of a partner in collaboration. This article is categorized under: Cognitive Biology > Evolutionary Roots of Cognition Psychology > Comparative Psychology.


Pendulum-based measurements reveal impact dynamics at the scale of a trap-jaw ant.
Small organisms can produce powerful, sub-millisecond impacts by moving tiny structures at high accelerations. We developed and validated a pendulum device to measure the impact energetics of microgram-sized trap-jaw ant mandibles accelerated against targets at 105 m s-2 Trap-jaw ants (Odontomachus brunneus; 19 individuals, 212 strikes) were suspended on one pendulum and struck swappable targets that were either attached to an opposing pendulum or fixed in place. Mean post-impact kinetic energy (energy from a strike converted to pendulum motion) was higher with a stiff target (21.0-21.5 µJ) than with a compliant target (6.4-6.5 µJ). Target mobility had relatively little influence on energy transfer. Mean contact duration of strikes against stiff targets was shorter (3.9-4.5 ms) than against compliant targets (6.2-7.9 ms). Shorter contact duration was correlated with higher post-impact kinetic energy. These findings contextualize and provide an energetic explanation for the diverse, natural uses of trap-jaw ant strikes such as impaling prey, launching away threats and performing mandible-powered jumps. The strong effect of target material on energetic exchange suggests material interactions as an avenue for tuning performance of small, high acceleration impacts. Our device offers a foundation for novel research into the ecomechanics and evolution of tiny biological impacts and their application in synthetic systems.


Neurophysiological signatures of Alzheimer's disease and frontotemporal lobar degeneration: pathology versus phenotype.
The disruption of brain networks is characteristic of neurodegenerative dementias. However, it is controversial whether changes in connectivity reflect only the functional anatomy of disease, with selective vulnerability of brain networks, or the specific neurophysiological consequences of different neuropathologies within brain networks. We proposed that the oscillatory dynamics of cortical circuits reflect the tuning of local neural interactions, such that different pathologies are selective in their impact on the frequency spectrum of oscillations, whereas clinical syndromes reflect the anatomical distribution of pathology and physiological change. To test this hypothesis, we used magnetoencephalography from five patient groups, representing dissociated pathological subtypes and distributions across frontal, parietal and temporal lobes: amnestic Alzheimer's disease, posterior cortical atrophy, and three syndromes associated with frontotemporal lobar degeneration. We measured effective connectivity with graph theory-based measures of local efficiency, using partial directed coherence between sensors. As expected, each disease caused large-scale changes of neurophysiological brain networks, with reductions in local efficiency compared to controls. Critically however, the frequency range of altered connectivity was consistent across clinical syndromes that shared a likely underlying pathology, whilst the localization of changes differed between clinical syndromes. Multivariate pattern analysis of the frequency-specific topographies of local efficiency separated the disorders from each other and from controls (accuracy 62% to 100%, according to the groups' differences in likely pathology and clinical syndrome). The data indicate that magnetoencephalography has the potential to reveal specific changes in neurophysiology resulting from neurodegenerative disease. Our findings confirm that while clinical syndromes have characteristic anatomical patterns of abnormal connectivity that may be identified with other methods like structural brain imaging, the different mechanisms of neurodegeneration also cause characteristic spectral signatures of physiological coupling that are not accessible with structural imaging nor confounded by the neurovascular signalling of functional MRI. We suggest that these spectral characteristics of altered connectivity are the result of differential disruption of neuronal microstructure and synaptic physiology by Alzheimer's disease versus frontotemporal lobar degeneration.


Soil microbial community response to land use change in an agricultural landscape of western Kenya.
Tropical agroecosystems are subject to degradation processes such as losses in soil carbon, nutrient depletion, and reduced water holding capacity that occur rapidly resulting in a reduction in soil fertility that can be difficult to reverse. In this research, a polyphasic methodology has been used to investigate changes in microbial community structure and function in a series of tropical soils in western Kenya. These soils have different land usage with both wooded and agricultural soils at Kakamega and Ochinga, whereas at Ochinga, Leuro, Teso, and Ugunja a replicated field experiment compared traditional continuous maize cropping against an improved N-fixing fallow system. For all sites, principal component analysis of 16S rRNA gene denaturing gradient gel electrophoresis (DGGE) profiles revealed that soil type was the key determinant of total bacterial community structure, with secondary variation found between wooded and agricultural soils. Similarly, phospholipid fatty acid (PLFA) analysis also separated wooded from agricultural soils, primarily on the basis of higher abundance of monounsaturated fatty acids, anteiso- and iso-branched fatty acids, and methyl-branched fatty acids in the wooded soils. At Kakamega and Ochinga wooded soils had between five 5 and 10-fold higher levels of soil carbon and microbial biomass carbon than agricultural soils from the same location, whereas total enzyme activities were also lower in the agricultural sites. Soils with woody vegetation had a lower percentage of phosphatase activity and higher cellulase and chitinase activities than the agricultural soils. BIOLOG analysis showed woodland soils to have the greatest substrate diversity. Throughout the study the two functional indicators (enzyme activity and BIOLOG), however, showed lower specificity with respect to soil type and land usage than did the compositional indicators (DGGE and PLFA). In the field experiment comparing two types of maize cropping, both the maize yields and total microbial biomass were found to increase with the fallow system. Moreover, 16S rRNA gene and PLFA analyses revealed shifts in the total microbial community in response to the different management regimes, indicating that deliberate management of soils can have considerable impact on microbial community structure and function in tropical soils.


The visibility of color breakup and a means to reduce it.
Color breakup is an artifact seen on displays that present colors sequentially. When the eye tracks a moving object on such a display, different colors land on different places on the retina, and this gives rise to visible color fringes at the object's leading and trailing edges. Interestingly, color breakup is also observed when the eye is stationary and an object moves by. Using a novel psychophysical procedure, we measured breakup both when viewers tracked and did not track a moving object. Breakup was somewhat more visible in the tracking than in the non-tracking condition. The video frames contained three subframes, one each for red, green, and blue. We spatially offset the green and blue stimuli in the second and third subframes, respectively, to find the values that minimized breakup. In the tracking and non-tracking conditions, spatial offsets of Δx/3 in the second subframe (where Δx is the displacement of the object in one frame) and 2Δx/3 in the third eliminated breakup. Thus, this method offers a way to minimize or even eliminate breakup whether the viewer is tracking or not. We suggest ways to implement the method with real video content. We also developed a color-breakup model based on spatiotemporal filtering in color-opponent pathways in early vision. We found close agreement between the model's predictions and the experimental results. The model can be used to predict breakup for a wide variety of conditions.


De Novo Development of a Quantitative Adverse Outcome Pathway (qAOP) Network for Ultraviolet B (UVB) Radiation Using Targeted Laboratory Tests and Automated Data Mining.
Ultraviolet B (UVB) radiation is a natural nonchemical stressor posing potential hazards to organisms such as planktonic crustaceans. The present study was conducted to revisit the lethal effects of UVB on crustaceans, generate new experimental evidence to fill in knowledge gaps, and develop novel quantitative adverse outcome pathways (qAOPs) for UVB. A combination of laboratory and computational approaches was deployed to achieve the goals. For targeted laboratory tests, Daphnia magna was used as a prototype and exposed to a gradient of artificial UVB. Targeted bioassays were used to quantify the effects of UVB at multiple levels of biological organization. A toxicity pathway network was assembled based on the new experimental evidence and previously published data extracted using a novel computational tool, the NIVA Risk Assessment Database (NIVA RAdb). A network of AOPs was developed, and weight of evidence was assessed based on a combination of the current and existing data. In addition, quantitative key event relationships in the AOPs were developed by fitting the D. magna data to predefined models. A complete workflow for assembly and evaluation of qAOPs has been presented, which may serve as a good example for future de novo qAOP development for chemical and nonchemical stressors.


Light inhibition of leaf respiration in field-grown Eucalyptus saligna in whole-tree chambers under elevated atmospheric CO2 and summer drought.
We investigated whether the degree of light inhibition of leaf respiration (R) differs among large Eucalyptus saligna grown in whole-tree chambers and exposed to present and future atmospheric [CO(2) ] and summer drought. Associated with month-to-month changes in temperature were concomitant changes in R in the light (R(light) ) and darkness (R(dark) ), with both processes being more temperature dependent in well-watered trees than under drought. Overall rates of R(light) and R(dark) were not significantly affected by [CO(2) ]. By contrast, overall rates of R(dark) (averaged across both [CO(2) ]) were ca. 25% lower under drought than in well-watered trees. During summer, the degree of light inhibition of leaf R was greater in droughted (ca. 80% inhibition) than well-watered trees (ca. 50% inhibition). Notwithstanding these treatment differences, an overall positive relationship was observed between R(light) and R(dark) when data from all months/treatments were combined (R(2) = 0.8). Variations in R(light) were also positively correlated with rates of Rubisco activity and nitrogen concentration. Light inhibition resulted in a marked decrease in the proportion of light-saturated photosynthesis respired (i.e. reduced R/A(sat) ). Collectively, these results highlight the need to account for light inhibition when assessing impacts of global change drivers on the carbon economy of tree canopies.


Comparison of ammonia emissions related to nitrogen use efficiency of livestock production in Europe.
The increasing global demand for food and the environmental effects of reactive nitrogen losses in the food production chain, increase the need for efficient use of nitrogen (N). Of N harvested in agricultural plant products, 80% is used to feed livestock. Because the largest atmospheric loss of reactive nitrogen from livestock production systems is ammonia (NH3), the focus of this paper is on N lost as NH3 during the production of animal protein. The focus of this paper is to understand the key factors explaining differences in Nitrogen Use Efficiency (NUE) of animal production among various European countries. Therefore we developed a conceptual framework to describe the NUE defined as the amount of animal-protein N per N in feed and NH3-N losses in the production of milk, beef, pork, chicken meat and eggs in The Netherlands, Switzerland, United Kingdom, Germany, Austria and Denmark. The framework describes how manure management and animal-related parameters (feed, metabolism) relate to NH3 emissions and NUE. The results showed that the animal product with the lowest NUE had the largest NH3 emissions and vice versa, which agrees with the reciprocal relationship between NUE and NH3 within the conceptual framework. Across animal products for the countries considered, about 20% of the N in feed is lost as NH3. The significant smallest proportion (12%) of NH3-N per unit of Nfeed is from chicken production. The proportions for other products are 17%, 19%, 20% and 22% for milk, pork, eggs and beef respectively. These differences were not significantly different due to the differences among countries. For all countries, NUE was lowest for beef and highest for chicken. The production of 1 kg N in beef required about 5 kg N in feed, of which 1 kg N was lost as NH3-N. For the production of 1 kg N in chicken meat, 2 kg N in feed was required and 0.2 kg was lost as NH3. The production of 1 kg N in milk required 4 kg N in feed with 0.6 kg NH3-N loss, the same as pork and eggs, but those needed 3 and 3.5 kg N in feed per kg N in product respectively. Except for beef, the differences among these European countries were mainly caused by differences in manure management practices and their emission factors, rather than by animal-related factors including feed and digestibility influencing the excreted amount of ammoniacal N (TAN). For beef, both aspects caused important differences. Based on the results, we encourage the expression of N losses as per N in feed or per N in product, in addition to per animal place, when comparing production efficiency and NUE. We consider that disaggregating emission factors into a diet/animal effect and a manure management effect would improve the basis for comparing national NH3 emission inventories.


Disjunctive Normal Parametric Level Set With Application to Image Segmentation.
Level set methods are widely used for image segmentation because of their convenient shape representation for numerical computations and capability to handle topological changes. However, in spite of the numerous works in the literature, the use of level set methods in image segmentation still has several drawbacks. These shortcomings include formation of irregularities of the signed distance function, sensitivity to initialization, lack of locality, and expensive computational cost, which increases dramatically as the number of objects to be simultaneously segmented grows. In this paper, we propose a novel parametric level set method called disjunctive normal level set (DNLS), and apply it to both two-phase (single object) and multiphase (multiobject) image segmentations. DNLS is a differentiable model formed by the union of polytopes, which themselves are created by intersections of half-spaces. We formulate the segmentation algorithm in a Bayesian framework and use a variational approach to minimize the energy with respect to the parameters of the model. The proposed DNLS can be considered as an open framework that allows the use of different appearance models and shape priors. Compared with the conventional level sets available in the literature, the proposed DNLS has the following major advantages: it requires significantly less computational time and memory, it naturally keeps the level set function regular during the evolution, it is more suitable for multiphase and local region-based image segmentations, and it is less sensitive to noise and initialization. The experimental results show the potential of the proposed method.


Clinical nurse specialist: walking the wire.
Considered by many to be the panacea for all nursing's problems, the clinical nurse specialist (CNS) has only recently gained widespread recognition as a legitimate role in Australia. The CNS is the equivalent in other states and territories of the clinical nurse consultant, the charge nurse or the nurse unit manager. Implementation of the role has been complicated by inadequately delineated role functions, unrealistic expectations and limited recognition of clinical expertise. Using both quantitative and qualitative exploratory techniques it was found that three critical themes impinged in a negative way on the effectiveness of the CNS. These were role ambiguity, role overload and the 'paradox of power'. Maintaining clinical expertise in the practice setting is essential for high quality cost effective and autonomous nursing care and this can be provided through the effective implementation of the CNS role.


High functioning male with fragile X syndrome and fragile X-associated tremor/ataxia syndrome.
Fragile X syndrome (FXS) affects individuals with more than 200 CGG repeats (full mutation) in the fragile X mental retardation 1 (FMR1) gene. Those born with FXS experience cognitive and social impairments, developmental delays, and some features of autism spectrum disorders. Carriers of a premutation (55-200 CGG repeats) are generally not severely affected early in life; however, are at high risk of developing the late onset neurodegenerative disorder, Fragile X-associated Tremor/Ataxia Syndrome (FXTAS), or Fragile X-associated Primary Ovarian Insufficiency (FXPOI), and may have other medical conditions such as developmental delay, autism spectrum disorders, hypertension, anxiety, and immune-mediated disorders. Here we present a case of a 58-year-old man with a borderline IQ, average memory skills, and executive function deficits. He met criteria for multiple psychiatric diagnoses and presented with tremor and ataxia, meeting criteria for FXTAS. Molecular testing unveiled a completely unmethylated FMR1 full mutation in peripheral blood mononucleated cells with elevated FMR1 mRNA and premutation alleles of different sizes in two other tissues (primary fibroblasts and sperm), indicating the presence of allele instability based on both inter- and intra-tissue mosaicism. The observation of FXTAS in this case of a full mutation mosaic man suggests that the pathogenic mechanism underlying this disorder is not observed exclusively in premutation carriers as it was originally thought. The concomitant presence of features of FXS and late onset neurological deterioration with probable FXTAS likely result from a combined molecular pathology of elevated FMR1 mRNA levels, a molecular hallmark of FXTAS and low FMRP expression that leads to FXS.


Quantitative Proteomics of Enriched Esophageal and Gut Tissues from the Human Blood Fluke Schistosoma mansoni Pinpoints Secreted Proteins for Vaccine Development.
Schistosomes are blood-dwelling helminth parasites that cause schistosomiasis, a debilitating disease resulting in inflammation and, in extreme cases, multiple organ damage. Major challenges to control the transmission persist, and the discovery of protective antigens remains of critical importance for vaccine development. Rhesus macaques can self-cure following schistosome infection, generating antibodies that target proteins from the tegument, gut, and esophagus, the last of which is the least investigated. We developed a dissection technique that permitted increased sensitivity in a comparative proteomics profiling of schistosome esophagus and gut. Proteome analysis of the male schistosome esophagus identified 13 proteins encoded by microexon genes (MEGs), 11 of which were uniquely located in the esophageal glands. Based on this and transcriptome information, a QconCAT was designed for the absolute quantification of selected targets. MEGs 12, 4.2, and 4.1 and venom allergen-like protein 7 were the most abundant, spanning over 245 million to 6 million copies per cell, while aspartyl protease, palmitoyl thioesterase, and galactosyl transferase were present at <1 million copies. Antigenic variation by alternative splicing of MEG proteins was confirmed together with a specialized machinery for protein glycosylation/secretion in the esophagus. Moreover, some gastrodermal secretions were highly enriched in the gut, while others were more uniformly distributed throughout the parasite, potentially indicating lysosomal activity. Collectively, our findings provide a more rational, better-oriented selection of schistosome vaccine candidates in the context of a proven model of protective immunity.


Efficacy and Safety of MEDI2070, an Antibody Against Interleukin 23, in Patients With Moderate to Severe Crohn's Disease: A Phase 2a Study.
MEDI2070 is a human monoclonal antibody that selectively inhibits interleukin 23 (IL23), a cytokine implicated in the pathogenesis of Crohn's disease (CD). We analyzed its safety and efficacy in treatment of CD in a phase 2a study. We conducted a double-blind, placebo-controlled study of 119 adults with moderate to severe CD failed by treatment with tumor necrosis factor antagonists. Patients were randomly assigned (1:1) to groups given MEDI2070 (700 mg) or placebo intravenously at weeks 0 and 4. Patients received open-label MEDI2070 (210 mg) subcutaneously every 4 weeks from weeks 12 to 112. The CD Activity Index was used to measure disease activity. The primary outcome, clinical response (either a 100-point decrease in CD Activity Index score from baseline or clinical remission, defined as CD Activity Index score <150) at week 8 occurred in 49.2% of patients receiving MEDI2070 (n = 59) compared with 26.7% receiving placebo (n = 60; absolute difference, 22.5%; 95% confidence interval, 5.6%-39.5%; P = .010). Clinical response at week 24 occurred in 53.8% of patients who continued to receive open-label MEDI2070 and in 57.7% of patients who had received placebo during the double-blind period and open-label MEDI2070 thereafter. The most common adverse events were headache and nasopharyngitis. Higher baseline serum concentrations of IL22, a cytokine whose expression is induced by IL23, were associated with greater likelihood of response to MEDI2070 compared with placebo. In a phase 2a trial of patients with moderate to severe Crohn's disease who had failed treatment with tumor necrosis factor antagonists, 8 and 24 weeks of treatment with MEDI2070 were associated with clinical improvement. ClinicalTrials.gov ID: NCT01714726.


[Vaccine-related adverse reactions in immunocompromised patients and in special situations of a hospital Vaccine Unit].
The aim of the study was to describe the type of vaccines administered in the Vaccine Unit at a reference hospital. Calculate the overall and specific reporting rate of adverse reactions. Retrospective observational study for the period between November 2014 and November 2017, on patients who developed an adverse drug reaction (ADR) after the administration of a vaccine and who were notified to the Spanish Pharmacovigilance System. The variables analyzed were age, sex, risk group, vaccine class, co-administration and type of ADR. A univariate and bivariate analysis was performed. The global and vaccine specific rate of ADR notification was calculated. A total of 18,123 vaccines were administered, of which 20.7% corresponded to hepatitis B virus vaccine. Fifty-three RAM suspects were reported. In 64.2% of cases only one vaccine was administered. Inactivated vaccines accounted for 88.7% of notifications. The highest number of notifications was generated by the 23 serotypes pneumococcal polysaccharide vaccine. The overall reporting rate was 0.42%. The hexavalent vaccine had the highest reporting rate (2.81%). 49.1% of the ADR were systemic. The overall reporting rate was low but higher than that of other authors. Proper reporting of possible adverse post-vaccine reactions is essential to contribute to vaccine safety and to increase public confidence in vaccines.


Toll-like receptor responses in IRAK-4-deficient neutrophils.
Human neutrophils were found to express all known Toll-like receptors (TLRs) except TLR3 and TLR7. IRAK-4-deficient neutrophils were tested for their responsiveness to various TLR ligands. Essentially all TLR responses in neutrophils, including the induction of reactive oxygen species generation, adhesion, chemotaxis and IL-8 secretion, were found to be dependent on IRAK-4. Surprisingly, the reactivity towards certain established TLR ligands, imiquimod and ODN-CpG, was unaffected by IRAK-4 deficiency, demonstrating their activity is independent of TLR. TLR-4-dependent signaling in neutrophils was totally dependent on IRAK-4 without any major TRIF-mediated contribution. We did not observe any defects in killing capacity of IRAK-4-deficient neutrophils for Staphylococcus aureus, Escherichia coli and Candida albicans, suggesting that microbial killing is primarily TLR independent.


Use of antipsychotic drugs and mood stabilizers in women of childbearing age with schizophrenia and bipolar disorder: epidemiological survey.
Aims. To determine the prevalence of women of childbearing age with schizophrenia and bipolar disorder exposed to antipsychotic (AP) drugs and mood stabilizers (MS) in Lombardy, a European region of 10 million inhabitants and 1 752 285 women of childbearing age. Methods. The data concerning psychiatric care, drug treatments and pregnancy outcomes were retrieved from local administrative databases during a 12-month census period. Results. During a 12-month census period, 2893 women of childbearing age with schizophrenia (74.8% of all women of childbearing age with schizophrenia) and 918 with bipolar disorder (80.1% of all women of childbearing age with bipolar disorder) were exposed to AP drugs or MS, yielding a prevalence of exposure for women with schizophrenia of 1.65 (95% confidence interval (CI) 1.59-1.71) per 1000 female inhabitants, and for women with bipolar disorder of 0.52 (95% CI 0.49-0.55) per 1000 female inhabitants. Persistent exposure to potentially teratogenic medications accounted for one in every 1000 women of childbearing age. Of the 57 pregnancies in women with schizophrenia, normal delivery was recorded in 23 (40%) cases; of the 26 pregnancies in women with bipolar disorder, normal delivery was recorded in 10 (38%) cases. Conclusions. In women of childbearing age with severe mental disorders, exposure to psychotropic drugs is substantial, which suggests that the issue of reproductive health is epidemiologically relevant and a major public health concern.


Investigation of potential inhibitor properties of ethanolic propolis extracts against ACE-II receptors for COVID-19 treatment by molecular docking study.
The angiotensin-converting enzyme (ACE)-related carboxypeptidase, ACE-II, is a type I integral membrane protein of 805 amino acids that contains 1 HEXXH-E zinc binding consensus sequence. ACE-II has been implicated in the regulation of heart function and also as a functional receptor for the coronavirus that causes the severe acute respiratory syndrome (SARS). In this study, the potential of some flavonoids presents in propolis to bind to ACE-II receptors was calculated with in silico. Binding constants of ten flavonoids, caffeic acid, caffeic acid phenethyl ester, chrysin, galangin, myricetin, rutin, hesperetin, pinocembrin, luteolin and quercetin were measured using the AutoDock 4.2 molecular docking program. And also, these binding constants were compared to reference ligand of MLN-4760. The results are shown that rutin has the best inhibition potentials among the studied molecules with high binding energy - 8.04 kcal/mol, and it is followed by myricetin, quercetin, caffeic acid phenethyl ester and hesperetin. However, the reference molecule has binding energy of - 7.24 kcal/mol. In conclusion, the high potential of flavonoids in ethanolic propolis extracts to bind to ACE-II receptors indicates that this natural bee product has high potential for COVID-19 treatment, but this needs to be supported by experimental studies.


Errors and discrepancies in the administration of intravenous infusions: a mixed methods multihospital observational study.
Intravenous medication administration has traditionally been regarded as error prone, with high potential for harm. A recent US multisite study revealed few potentially harmful errors despite a high overall error rate. However, there is limited evidence about infusion practices in England and how they relate to prevalence and types of error. To determine the prevalence, types and severity of errors and discrepancies in infusion administration in English hospitals, and to explore sources of variation, including the contribution of smart pumps. We conducted an observational point prevalence study of intravenous infusions in 16 National Health Service hospital trusts. Observers compared each infusion against the medication order and local policy. Deviations were classified as errors or discrepancies based on their potential for patient harm. Contextual issues and reasons for deviations were explored qualitatively during observer debriefs. Data were collected from 1326 patients and 2008 infusions. Errors were observed in 231 infusions (11.5%, 95% CI 10.2% to 13.0%). Discrepancies were observed in 1065 infusions (53.0%, 95% CI 50.8% to 55.2%). Twenty-three errors (1.1% of all infusions) were considered potentially harmful; none were judged likely to prolong hospital stay or result in long-term harm. Types and prevalence of errors and discrepancies varied widely among trusts, as did local policies. Deviations from medication orders and local policies were sometimes made for efficiency or patient need. Smart pumps, as currently implemented, had little effect, with similar error rates observed in infusions delivered with and without a smart pump (10.3% vs 10.8%, p=0.8). Errors and discrepancies are relatively common in everyday infusion administrations but most have low potential for patient harm. Better understanding of performance variability to strategically manage risk may be a more helpful tactic than striving to eliminate all deviations.


Management of pelvic fracture-associated urethral injuries: A survey of Canadian urologists.
The management of pelvic fracture-associated urethral injuries (PFUI) is not standardized and optimal management is controversial. We surveyed Canadian urologists about their experiences and opinions regarding optimal management of PFUI. Canadian urologists were surveyed via an anonymous, bilingual, web-based, 12-item questionnaire. A total of 735 Canadian urologists were invited to participate via email distributed by the Canadian Urological Association. Of the 146 urologists who participated (19.9% response rate), the majority practice at a trauma centre (53.2%), but manage only 1-5 PFUI/year (71.5%). Most participants (82.6%) favour primary realignment compared to suprapubic (SP) tube with delayed repair (15.3%) and immediate reconstruction (2.1%). Compared to SP diversion and delayed repair, the majority of participants believe primary realignment is associated with equivocal incontinence (61.2%) and erectile dysfunction rates (75.8%), but has lower stricture rates (73.0%). Among respondents who perform primary realignment, 45.4% concurrently place a SP tube, while 54.6% do not. While 91% believe SP tubes do not increase the risk of pelvic hardware infections, 31.6% report that orthopedic surgeons alter their management of pelvic fractures in the presence of a SP tube. Most Canadian urologist respondents - even those practicing at trauma centres - manage very few PFUIs/year. There is reasonable consensus among respondents that primary realignment is favourable to delayed or immediate reconstruction, but discordance on whether or not to place concurrent SP tubes. The urological and orthopedic consequences of SP tubes in the management of traumatic urological injuries warrant further investigation.


A 6-Mb high-resolution physical and transcription map encompassing the hereditary prostate cancer 1 (HPC1) region.
Several hereditary disease loci have been genetically mapped to the chromosome 1q24-q31 interval, including the hereditary prostate cancer 1 (HPC1) locus. Here, we report the construction of a 20-Mb yeast artificial chromosome contig and a high-resolution 6-Mb sequence-ready bacterial artificial chromosome (BAC)/P1-derived artificial chromosome (PAC) contig of 1q25 by sequence and computational analysis, STS content mapping, and chromosome walking. One hundred thirty-six new STSs, including 10 novel simple sequence repeat polymorphisms that are being used for genetic refinement of multiple disease loci, have been generated from this contig and are shown to map to the 1q25 interval. The integrity of the 6-Mb BAC/PAC contig has been confirmed by restriction fingerprinting, and this contig is being used as a template for human chromosome 1 genome sequencing. A transcription mapping effort has resulted in the precise localization of 18 known genes and 31 ESTs by database searching, exon trapping, direct cDNA hybridization, and sample sequencing of BACs from the 1q25 contig. An additional 11 known genes and ESTs have been placed within the larger 1q24-q31 interval. These transcription units represent candidate genes for multiple hereditary diseases, including HPC1.


Umbilical catheters as vectors for generalized bacterial infection in premature infants regardless of antibiotic use.
Introduction. Umbilical catheterization offers unique vascular access that is only possible in the neonatal setting due to unobstructed umbilical vessels from foetal circulation. With the cut of the umbilical cord, two arteries and a vein are dissected, allowing quick and painless catheterization of the neonate. Unfortunately, keeping the umbilical access sterile is challenging due to its mobility and necrosis of the umbilical stump, which makes it a perfect model for vessel catheter colonization analysis.Aim. The aim of this study was to evaluate bacterial colonization of the umbilical catheter, with a focus on the difference between various sections of the catheter, the duration of catheterization, patient status and gestational age.Methodology. We performed bacterial cultures for 44 umbilical catheters, analysing the superficial and deep parts of the catheter separately, and revealed colonization in one-third of cases.Results. One hundred per cent of the colonization occurred in preterm infants, with a shift towards extreme prematurity. The catheters were mainly colonized by coagulase-negative staphylococci. The majority of catheters presented with superficial colonization dominance, and there were no cases of deep colonization. The bacterial strains and their resistance were consistent between the catheter's proximal and distal parts, as well as positive blood cultures. The patients with the most intense bacterial catheter colonization presented with sepsis around removal time or a couple of days later, especially if they were extremely premature and exhibited very low birth weight. Catheterization time did not play a major role.Conclusion. Umbilical catheters are vectors for skin microflora transmission to the bloodstream via biofilm formation, regardless of antibiotic use and the duration of catheterization, especially in preterm neonates.


Deletion of a phenylalanine in the N-terminal region of human cytochrome P-450(17 alpha) results in partial combined 17 alpha-hydroxylase/17,20-lyase deficiency.
Steroid 17 alpha-hydroxylase and 17,20-lyase activities reside within the same polypeptide chain (cytochrome P-450(17 alpha)), and consequently human 17 alpha-hydroxylase deficiencies are characterized by defects in either or both of these activities. Human mutants having these deficiencies represent an excellent source of material for investigation of P-450(17 alpha) structure-function relationships. The CYP17 gene from an individual having partial combined 17 alpha-hydroxylase/17,20-lyase deficiency has been characterized structurally and the homozygous mutation found to be the deletion of the phenylalanine codon (TTC) at either amino acid position 53 or 54 in exon 1. Reconstruction of this mutation into a human P-450(17 alpha) cDNA followed by expression in COS 1 cells led to production of the same amount of immunodetectable P-450(17 alpha) protein as found with expression of the normal human P-450(17 alpha) cDNA. However, 17 alpha-hydroxylase activity of this mutant protein measured in intact cells was less than 37% of that observed upon expression of the wild-type enzyme, whereas 17,20-lyase activity of the mutant was less than 8% of that observed with the normal enzyme. When estimated in intact cells, the Km for 17 alpha-hydroxylation of progesterone was increased by a factor of 2 in the mutant enzyme, whereas the Vmax was reduced by a factor of 3. In order to estimate the kinetic parameters for the 17,20-lyase reaction, microsomes were isolated from transfected COS 1 cells to enrich for this activity. Surprisingly, the specific activity of the mutant 17 alpha-hydroxylase in microsomes was 3-fold less than that observed in intact cells, indicating that the structure of mutant P-450(17 alpha) was dramatically altered upon disruption of COS 1 cells. Apparently the deletion of a single phenylalanine in the N-terminal region of P-450(17 alpha) alters its folding in such a way that both enzymatic activities are dramatically decreased, leading to the partial combined deficiency observed in this individual.


A randomized trial comparing part-time patching with observation for children 3 to 10 years of age with intermittent exotropia.
To determine the effectiveness of prescribed part-time patching for treatment of intermittent exotropia (IXT) in children. Multicenter, randomized clinical trial. Three hundred fifty-eight children 3 to <11 years of age with previously untreated (except for refractive correction) IXT and near stereoacuity of 400 seconds of arc or better were enrolled. Intermittent exotropia met the following criteria: (1) IXT at distance OR constant exotropia at distance and either IXT or exophoria at near; (2) exodeviation (tropia or phoria) of at least 15 prism diopters (PD) at distance or near by prism and alternate cover test (PACT); and (3) exodeviation of at least 10 PD at distance by PACT. Participants were assigned randomly either to observation (no treatment for 6 months) or to patching for 3 hours daily for 5 months, with a 1-month washout period of no patching before the 6-month primary outcome examination. The primary outcome was deterioration at either the 3-month or the 6-month follow-up visit, defined as: (1) constant exotropia measuring at least 10 PD at distance and near by simultaneous prism and cover test, and/or (2) near stereoacuity decreased by at least 2 octaves from baseline, both assessed by a masked examiner and confirmed by a retest. Participants who were prescribed any nonrandomized treatment without first meeting either deterioration criteria also were counted as having deteriorated. Of the 324 participants (91%) completing the 6-month primary outcome examination, deterioration occurred in 10 of the 165 participants (6.1%) in the observation group (3 of these 10 started treatment without meeting deterioration criteria) and in 1 of the 159 participants (0.6%) in the part-time patching group (difference, 5.4%; lower limit of 1-sided exact 95% confidence interval, 2.0%; P = 0.004, 1-sided hypothesis test). Deterioration of previously untreated childhood IXT over a 6-month period is uncommon with or without patching treatment. Although there is a slightly lower deterioration rate with patching, both management approaches are reasonable for treating children 3 to 10 years of age with IXT.


In vivo evaluation of thiolated chitosan tablets for oral insulin delivery.
Chitosan-6-mercaptonicotinic acid (chitosan-6-MNA) is a thiolated chitosan with strong mucoadhesive properties and a pH-independent reactivity. This study aimed to evaluate the in vivo potential for the oral delivery of insulin. The comparison of the nonconjugated chitosan and chitosan-6-MNA was performed on several studies such as mucoadhesion, release, and in vivo studies. Thiolated chitosan formulations were both about 80-fold more mucoadhesive compared with unmodified ones. The thiolated chitosan tablets showed a sustained release for 5 h for the polymer of 20 kDa and 8 h for the polymer of 400 kDa. Human insulin was quantified in rats' plasma by means of ELISA specific for human insulin with no cross-reactivity with the endogenous insulin. In vivo results showed thiolation having a tremendous impact on the absorption of insulin. The absolute bioavailabilities were 0.73% for chitosan-6-MNA of 20 kDa and 0.62% for chitosan-6-MNA 400 kDa. The areas under the concentration-time curves (AUC) of chitosan-6-MNA formulations compared with unmodified chitosan were 4.8-fold improved for the polymer of 20 kDa and 21.02-fold improved for the polymer of 400 kDa. The improvement in the AUC with regard to the most promising aliphatic thiomer was up to 6.8-fold. Therefore, chitosan-6-MNA represents a promising excipient for the oral delivery of insulin.


Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.
Streptococcus pneumoniae [Sp] infection is associated with local and systemic disease. Our current understanding of the differential contributions of genetic strain variation, serotype, and host response to disease phenotype is incomplete. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437); eleven of the thirteen strains have been genomically sequenced. For each strain 100 colony forming units were injected bilaterally into the tympanic bullae of 6 young adult chinchillas under general anesthesia. All animals were examined daily for local and systemic disease by a blinded observer. Pneumatic otoscopy was used to evaluate local disease, and behavioral assessments served as the measure of systemic disease. Virulence scoring was performed using a 4-point scale to assess four clinical parameters [severity and rapidity of local disease onset; and severity and rapidity of systemic disease onset] during a 10-day evaluation period. Highly significant variation was observed among the strains in their ability to cause disease and moribundity. As expected, there was a significant correlation between the rapidity of systemic disease onset and severity of systemic disease; however, there was little correlation between the severity of otoscopic changes and severity of systemic disease. Importantly, it was observed that different strains of the same serotype produced as broad an array of disease phenotypes as did strains of different serotypes. We attribute these phenotypic differences among the strains to the high degree of genomic plasticity that we have previously documented.


A fluorescence-based microbial sensor for the selective detection of gold.
This study presents a fluorescence-based microbial sensor for the detection of metal ions as a novel analytical tool for environmental applications. Our results demonstrate the effectiveness of whole-cell sensors in the selective detection of gold ions. Two heavy-metal-tolerant proteobacteria, Cupriavidus metallidurans and Ralstonia eutropha, were examined and showed great specificity. This work highlights the potential of employing engineered microbial strains as robust analytical tools.


Proximal Tibia Reconstruction After Bone Tumor Resection: Are Survivorship and Outcomes of Endoprosthetic Replacement and Osteoarticular Allograft Similar?
The proximal tibia is one of the most challenging anatomic sites for extremity reconstructions after bone tumor resection. Because bone tumors are rare and large case series of reconstructions of the proximal tibia are lacking, we undertook this study to compare two major reconstructive approaches at two large sarcoma centers. The purpose of this study was to compare groups of patients treated with endoprosthetic replacement or osteoarticular allograft reconstruction for proximal tibia bone tumors in terms of (1) limb salvage reconstruction failures and risk of amputation of the limb; (2) causes of failure; and (3) functional results. Between 1990 and 2012, two oncologic centers treated 385 patients with proximal tibial resections and reconstruction. During that time, the general indications for those types of reconstruction were proximal tibia malignant tumors or bone destruction with articular surface damage or collapse. Patients who matched the inclusion criteria (age between 15 and 60 years old, diagnosis of a primary bone tumor of the proximal tibia treated with limb salvage surgery and reconstructed with endoprosthetic replacement or osteoarticular allograft) were included for analysis (n = 149). In those groups (endoprosthetic or allograft), of the patients not known to have reached an endpoint (death, reconstructive failure, or limb loss) before 2 years, 85% (88 of 104) and 100% (45 of 45) were available for followup at a minimum of 2 years. A total of 88 patients were included in the endoprosthetic group and 45 patients in the osteoarticular allograft group. Followup was at a mean of 9.5 (SD 6.72) years (range, 2-24 years) for patients with endoprosthetic reconstructions, and 7.4 (SD 5.94) years for patients treated with allografts (range, 2-21 years). The following variables were compared: limb salvage reconstruction failure rates, risk of limb amputation, type of failures according to the Henderson et al. classification, and functional results assessed by the Musculoskeletal Tumor Society system. With the numbers available, after competitive risk analysis, the probability of failure for endoprosthetic replacement of the proximal tibia was 18% (95% confidence interval [CI], 10.75-27.46) at 5 years and 44% (95% CI, 31.67-55.62) at 10 years and for osteoarticular allograft reconstruction was 27% (95% CI, 14.73-40.16) at 5 years and 32% (95% CI, 18.65-46.18) at 10 years. There were no differences in terms of risk of failures at 5 years (p = 0.26) or 10 years (p = 0.20) between the two groups. Fifty-one of 88 patients (58%) with proximal tibia endoprostheses developed a reconstruction failure with mechanical causes being the most prevalent (32 of 51 patients [63%]). A total of 19 of 45 osteoarticular allograft reconstructions failed (42%) and nine of 19 (47%) of them were caused by early infection. Ten-year risk of amputation after failure for endoprosthetic reconstruction was 10% (95% CI, 5.13-18.12) and 11% (95% CI, 4.01-22.28) for osteoarticular allograft with no difference between the groups (p = 0.91). With the numbers available, there were no differences between the groups in terms of the mean Musculoskeletal Tumor Society score (26.58, SD 2.99, range, 19-30 versus 27.52, SD 1.91, range, 22-30; p = 0.13; 95% CI, -2,3 to 0.32). Mean extension lag was more severe in the endoprosthetic group than the osteoarticular allograft group: 13.56° (SD 18.73; range, 0°-80°) versus 2.41° (SD 5.76; range, 0°-30°; p < 0.001; 95% CI, 5.8-16.4). Reconstruction of the proximal tibia with either endoprosthetic replacement or osteoarticular allograft appears to offer similar reconstruction failures rates. The primary cause of failure for allograft was infection and for endoprosthesis was mechanical complications. We believe that the treating surgeon should have both options available for treatment of patients with malignant or aggressive tumors of the proximal tibia. (S)he might consider an allograft in a younger patient to achieve better extensor mechanism function, whereas in an older patient or one with a poorer prognosis where return to function and ambulation quickly is desired, an endoprosthesis may be advantageous. Level III, therapeutic study.


Hydrochlorothiazide-induced noncardiogenic pulmonary edema: an underrecognized yet serious adverse drug reaction.
Noncardiogenic pulmonary edema is a rare but potentially life-threatening complication of hydrochlorothiazide therapy. We describe three patients who developed this serious adverse reaction. A 64-year-old woman developed dypsnea and hypotension within 60 minutes of taking a single dose of hydrochlorothiazide 25 mg. She was admitted to the critical care unit with acute respiratory failure and subsequent multiple-organ dysfunction. The second patient was a 56-year-old woman who experienced sudden onset of shortness of breath that developed 10 minutes after taking a single dose of hydrochlorothiazide 25 mg. The third was a 59-year-old woman who developed sudden onset of shortness of breath, nausea, vomiting, and diarrhea after her first dose of hydrochlorothiazide-triamterene. All three women had a history of a similar, albeit minor, reaction to a thiazide diuretic. Review of the literature identified 36 additional cases of noncardiogenic pulmonary edema after thiazide use. The patients developed symptoms 10-150 minutes after ingestion of hydrochlorothiazide or another thiazide. Symptoms can occur on first exposure to the drug or in patients taking the drug intermittently. Of interest, 90% of documented cases occurred in women. With the increasing use of thiazide diuretics in the treatment of hypertension, clinicians need to be aware of the possible association of these drugs with the development of noncardiogenic pulmonary edema.


The effect of diabetes on the risk of endometrial Cancer: an updated a systematic review and meta-analysis.
Previous studies conducted on the association between diabetes and the risk of endometrial cancer have reported controversial results that have raised a variety of questions about the association between diabetes and the incidence of this cancer. Thus, the aim of this systematic review and meta-analysis was to more precisely estimate the effect of diabetes on the risk of endometrial cancer incidence. All original articles were searched in international databases, including Medline (PubMed), Web of sciences, Scopus, EMBASE, and CINHAL. Search was done from January 1990 to January 2018 without language limitations. Also, logarithm and standard error logarithm relative risk (RR) were used for meta-analysis. A total of 22 cohort and case-control studies were included in this meta-analysis, of which 14 showed statistically significant associations between diabetes and risk of endometrial cancer. Diabetes was associated with increased risk of endometrial cancer (RR = 1.72, 95% CI 1.48-2.01). The summary of RR for all 9 cohort studies was 1.56 (95% CI 1.21-2.01), and it was 1.85 (95% CI 1.53-2.23) for 13 case control studies. The summary of RR in hospital-based studies was higher than other studies. Thirteen of the primary studies-controlled BMI as a confounding variable, and the combined risk of their results was 1.62 (95% CI 1.34-1.97). Diabetes seems to increases the risk of endometrial cancer in women, and this finding can be useful in developing endometrial cancer prevention plans for women having diabetes.


Quantification of DNA repair capacity in whole blood of patients with head and neck cancer and healthy donors by comet assay.
Comet assay has been used to estimate cancer risk by quantification of DNA damage and repair in response to mutagen challenge. Our goal was to adopt best practices for the alkaline comet assay to measure DNA repair capacity of white blood cells in whole blood of patients with squamous cell carcinoma of the head and neck (HNSCC). The results show that initial damage by 10 Gy of gamma radiation expressed as percent DNA in comet tail was higher in stimulated lymphocytes (61.1+/-11.8) compared to whole blood (43.0+/-12.1) but subsequent repair was similar with comet tail of approximately 20% at 15 min and 13% at 45 min after exposure. Exposure of whole blood embedded in agarose from 5 to 10 Gy gamma radiation was followed by an approximately 70% repair of the DNA damage within 45 min with a faster repair phase in the first 15 min. Variability of the measurement was lower within repeated measurements of the same person compared to measurement of different healthy individuals. The repair during first 15 min was slower (p=0.01) in ex-/non-smokers (41.0+/-2.1%) compared to smokers (50.3+/-2.7%). This phase of repair was also slower (p=0.02) in HNSCC patients (36.8+/-2.1%) compared to controls matched on age and smoking (46.4+/-3.0%). The results of this pilot study suggest that quantification of repair in whole blood following a gamma radiation challenge is feasible. Additional method optimization would be helpful to improve the assay for a large population screening.


Energetic problems faced by micro-organisms growing or surviving on parsimonious energy sources and at acidic pH: I. Acidithiobacillus ferrooxidans as a paradigm.
The mitochondrial paradigm for a chemiosmotic energy transduction mechanism requires frequently misunderstood modifications for application to microbes growing and surviving at acidic pH values and/or with relatively weak reductants as energy sources. Here the bioenergetics of the iron oxidiser Acidithiobacillus ferrooxidans are reviewed and analysed so as to develop the general bioenergetic principles for understanding organisms that grow under these conditions. Extension of the principles outlined herein to organisms that survive (as opposed to grow) under these conditions is to be presented in a subsequent article.


Protein Kinetics and Metabolic Effects Related to Disease States in the Intensive Care Unit.
Evaluating protein kinetics in the critically ill population remains a very difficult task. Heterogeneity in the intensive care unit (ICU) population and wide spectrum of disease processes creates complexity in assessing protein kinetics. Traditionally, protein has been delivered in the context of total energy. Focus on energy delivery has recently come into question, as the importance of supplemental protein in patient outcomes has been shown in several recent trials. The ICU patient is prone to catabolism, immobilization, and impaired immunity, which is a perfect storm for massive loss of lean body tissue with a unidirectional flow of amino acids from muscle to immune tissue for immunoglobulin production, as well as liver for gluconeogenesis and acute phase protein synthesis. The understanding of protein metabolism in the ICU has been recently expanded with the discovery of how the mammalian target of rapamycin complex 1 is regulated. The concept of "anabolic resistance" and identifying the quantity of protein required to overcome this resistance is gaining support among critical care nutrition circles. It appears that a minimum of at least 1.2 g/kg/d with levels up to 2.0 g/kg/d of protein or amino acids appears safe for delivery in the ICU setting and may yield a better clinical outcome.


USA study of sex toy use by HIV-positive men who have sex with other men: implications for sexual health.
HIV/AIDS disproportionately impacts men who have sex with men (MSM) in the USA. Most existing literature on MSM with HIV focuses on transmission risk, but does not acknowledge health-promoting sexual behaviours men may undertake. This study examined sex toy use within this population to describe the extent to which using toys is incorporated into their sexual repertoires as a risk reduction practice. Data regarding sociodemographics, sexual/health-related behaviours and sex toy use were collected from 2275 MSM using an online survey. Most participants reported being sexually active (88.5%), and the majority (70.2%) of participants reported sex toy use within the previous year. Sex toy users were more likely to be white, in sexual relationships with others, and reported higher levels of sexual satisfaction. Given that sex toy use is common among this population, room for discussion exists about sex toys as tools to enhance pleasure and reduce HIV/sexually transmitted infection (STI) transmission.


ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions.
The International League Against Epilepsy (ILAE) Task Force on Nosology and Definitions proposes a classification and definition of epilepsy syndromes in the neonate and infant with seizure onset up to 2 years of age. The incidence of epilepsy is high in this age group and epilepsy is frequently associated with significant comorbidities and mortality. The licensing of syndrome specific antiseizure medications following randomized controlled trials and the development of precision, gene-related therapies are two of the drivers defining the electroclinical phenotypes of syndromes with onset in infancy. The principal aim of this proposal, consistent with the 2017 ILAE Classification of the Epilepsies, is to support epilepsy diagnosis and emphasize the importance of classifying epilepsy in an individual both by syndrome and etiology. For each syndrome, we report epidemiology, clinical course, seizure types, electroencephalography (EEG), neuroimaging, genetics, and differential diagnosis. Syndromes are separated into self-limited syndromes, where there is likely to be spontaneous remission and developmental and epileptic encephalopathies, diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. The emerging class of etiology-specific epilepsy syndromes, where there is a specific etiology for the epilepsy that is associated with a clearly defined, relatively uniform, and distinct clinical phenotype in most affected individuals as well as consistent EEG, neuroimaging, and/or genetic correlates, is presented. The number of etiology-defined syndromes will continue to increase, and these newly described syndromes will in time be incorporated into this classification. The tables summarize mandatory features, cautionary alerts, and exclusionary features for the common syndromes. Guidance is given on the criteria for syndrome diagnosis in resource-limited regions where laboratory confirmation, including EEG, MRI, and genetic testing, might not be available.


Occupational Therapy Practitioners' Perceptions About Older Adults With Developmental Disabilities in Traditional Health Care Settings.
Health care providers' knowledge of and comfort working with adults with developmental disabilities (DD) affect the quality of care this growing population receives. Previous research on this topic has not included occupational therapy practitioners. To determine occupational therapy practitioners' views about working with older adults with DD in traditional health care settings. Quantitative survey over 4 mo. A random sample of 310 practitioners from the American Occupational Therapy Association's Gerontology and Physical Disabilities Special Interest Sections working in traditional health care settings. A researcher-developed survey to assess occupational therapy practitioners' comfort, knowledge, challenge, and supports and barriers in regard to working with older adults with DD. In the 310 included surveys (31% response rate), most occupational therapy practitioners reported feeling comfortable (76.1%-80.0%) and knowledgeable (66.5%-68.4%) working with older adults with DD. Approximately 93% reported that work with older adults with DD was at least somewhat challenging. Key perceived barriers included clients' cognitive needs, lack of caregiver collaboration, and challenging behavior. Most occupational therapy practitioners in traditional health care settings found working with older adults with DD challenging, and many did not feel sufficiently knowledgeable to meet the needs of this population. Similar to other health professionals, occupational therapy practitioners may benefit from additional resources to provide services to this population. Older adults with DD receive occupational therapy services in hospitals, rehabilitation centers, nursing homes, and other medical settings. Because clients such as these are not common in these settings, occupational therapy practitioners who work there would like more tools to help provide good care.


Differentiated thyroid cancer: "complete" rational approach.
Controversy continues regarding the optimal management of patients with differentiated thyroid cancer because no prospective randomized studies evaluating the merits of (1) extent of thyroidectomy, (2) postoperative radioactive iodine ablation, or (3) thyroid-stimulating hormone (TSH) suppressive therapy exist. Patients with low risk differentiated thyroid cancer enjoy a relatively good prognosis with a mortality rate of about 2% to 5% and a recurrence rate of about 20%. Despite the excellent prognosis in patients considered to be at low risk, total or near-total thyroidectomy in patients with differentiated thyroid cancer has the advantages that: (1) postoperative radioactive iodine can be used to detect and treat residual normal thyroid tissue and local or distant metastases; (2) follow-up serum thyroglobulin levels are a more sensitive marker of persistent or recurrent disease when all thyroid tissue has been removed; and (3) total or near-total thyroidectomy with postoperative (131)I ablation and TSH suppressive therapy is associated with better survival and lower recurrence rates. Patients with occult papillary thyroid cancer and minimally invasive follicular thyroid cancer can be treated by thyroid lobectomy because they have a near-normal life expectancy. Virtually all other patients with differentiated thyroid cancer appear to benefit from more extensive initial treatment.