The influence of personality and perceived stress on the development of breast cancer: 20-year follow-up of 29,098 Japanese women.
Breast cancer is the most common cancer in women. However, it remains unproven whether psychological factors have an influence on breast cancer incidence. In our earlier study, subjects possessing two personality traits, decisiveness and "ikigai" (a Japanese word meaning something that makes one's life worth living), showed a significantly lower risk of developing breast cancer, although no psychological factors have been convincingly demonstrated to have an influence on breast cancer development in other studies. Therefore, we conducted this follow-up analysis to confirm the association between breast cancer incidence and psychological traits, using the final dataset of a large-scale prospective cohort study in Japan. We identified 209 cases of incident breast cancer out of a maximum 21-year follow-up of 29,098 Japanese women. Cox proportional hazard regression analysis, adjusted for the same potential confounders used in our previous study, did not reveal any significant relationships between breast cancer incidence and four psychological traits: having "ikigai", decisiveness, ease of anger arousal, and perceived stress. Our finding is consistent with previous studies, and suggests that the psychological traits are unlikely to be an important risk factor for breast cancer.


Innovative two-step negative selection of granulocyte colony-stimulating factor-mobilized circulating progenitor cells: adequacy for autologous and allogeneic transplantation.
A major obstacle in purifying either autologous or allogeneic hematopoietic stem cells from granulocyte colony-stimulating factor (G-CSF) mobilized circulating progenitor cells (CPC) is represented by the huge cellularity present in each apheretic product. To obtain a significant debulking of unwanted cells from the leukapheresis, we developed a modified protocol of immune rosetting whereby human ABO-Rh- compatible red blood cells (RBCs) are treated with chromium chloride and then coated with murine monoclonal antibodies (MoAbs) against leukocyte antigens. When experiments were performed with leukaphereses obtained from normal donors or from T-cell acute lymphoblastic leukemia (T-ALL) patients, RBCs were coated with murine MoAbs against human mature myeloid cells (CD11b) and T cells (CD6); whereas, in the case of patients with B-precursor ALL, B-cell non-Hodgkin's lymphoma (B-NHL), or multiple myeloma (MM), RBCs were coated with anti-CD11b only. After incubation with CPC, rosetting cells (myeloid precursor cells, granulocytes, monocytes, and T cells) were removed by Ficoll-Hypaque density gradient centrifugation with a blood cell processor apparatus, COBE (Lakewood, CO) 2991. After this step, a significant reduction of the initial cellularity was consistently obtained (range, 72% to 97%), whereas the median absolute recovery of the CD34+ cells was above 85% (range, 64 to 100), with a 10-fold relative enrichment ranging from 3% to 41%. In a second step, CPC can be further purged of contaminating T or B cells by incubation with lymphoid-specific magnetic microbeads (anti-CD2 and -CD7 to remove T cells; anti-CD19 to remove B cells) and elution through a type-D depletion column (composed of ferromagnetic fiber) inserted within a SuperMACS separator device (Miltenyi Biotech, Bergisch-Gladbach, Germany). By this approach, a highly effective (three to four logs) T-cell depletion was achieved in all experiments performed with normal donors or T-ALL patients (median loss of CD3+ cells: 99.8% [range 99.2 to 100]) and an equally efficient B-cell depletion was obtained from B-precursor ALL, B-NHL, or MM patients. At the end of the procedure the T- or B-cell depleted fraction retained a high proportion of the initial hematopoietic CD34+ stem cells, with a median recovery above 70% (range 48% to 100%) and an unmodified clonogenic potential. In five patients (two follicular NHL and three ALL) the purified fraction of stem cells was found disease free at the molecular level as assessed by polymerase chain reaction (PCR) analysis of the t(14;18) chromosome translocation or clono-specific DNA sequences of IgH or T-cell receptor gamma and delta chain genes. Purified autologous and allogeneic CPCs were transplanted in three and six patients, respectively, who showed a prompt and sustained hematologic engraftment. In conclusion, this method represents a simple and reproducible two-step procedure to obtain a highly efficient purging of T or B cells from G-CSF expanded and mobilized CPCs. This approach might lead to the eradication of the neoplastic clone in the autologous stem cell inoculum as well as for T-cell depletion during allogeneic transplantation.


The impact of reconstruction and scanner characterisation on the diagnostic capability of a normal database for [123I]FP-CIT SPECT imaging.
The use of a normal database for [123I]FP-CIT SPECT imaging has been found to be helpful for cases which are difficult to interpret by visual assessment alone, and to improve reproducibility in scan interpretation. The aim of this study was to assess whether the use of different tomographic reconstructions affects the performance of a normal [123I]FP-CIT SPECT database and also whether systems benefit from a system characterisation before a database is used. Seventy-seven [123I]FP-CIT SPECT studies from two sites and with 3-year clinical follow-up were assessed quantitatively for scan normality using the ENC-DAT normal database obtained in well-documented healthy subjects. Patient and normal data were reconstructed with iterative reconstruction with correction for attenuation, scatter and septal penetration (ACSC), the same reconstruction without corrections (IRNC), and filtered back-projection (FBP) with data quantified using small volume-of-interest (VOI) (BRASS) and large VOI (Southampton) analysis methods. Test performance was assessed with and without system characterisation, using receiver operating characteristics (ROC) analysis for age-independent data and using sensitivity/specificity analysis with age-matched normal values. The clinical diagnosis at follow-up was used as the standard of truth. There were no significant differences in the age-independent quantitative assessment of scan normality across reconstructions, system characterisation and quantitative methods (ROC AUC 0.866-0.924). With BRASS quantification, there were no significant differences between the values of sensitivity (67.4-83.7%) or specificity (79.4-91.2%) across all reconstruction and calibration strategies. However, the Southampton method showed significant differences in sensitivity between ACSC (90.7%) vs IRNC (76.7%) and FBP (67.4%) reconstructions with calibration. Sensitivity using ACSC reconstruction with this method was also significantly better with calibration than without calibration (65.1%). Specificity using the Southampton method was unchanged across reconstruction and calibration choices (82.4-88.2%). The ability of a normal [123I]FP-CIT SPECT database to assess clinical scan normality is equivalent across all reconstruction, system characterisation, and quantification strategies using BRASS quantification. However, when using the Southampton quantification method, performance is sensitive to the reconstruction and calibration strategy used.


Double diels-alder reactions of linear conjugated tetraenes.
[reaction: see text] Linear conjugated tetraenes are shown to participate effectively as bis-dienes in sequences involving either two intermolecular Diels-Alder reactions or an intramolecular followed by an intermolecular Diels-Alder reaction. Thus, simple tetraenol 1 is transformed into tetracyclic products 5, 6, and 9 in high yielding and highly stereoselective sequences with maleic anhydride involving the formation of three rings, four C-C bonds and one C-O bond, and eight stereocenters. In the latter case, the one-pot reaction protocol is very simple, and furnishes a single diastereoisomeric product in essentially quantitative yield. Linear conjugated tetraenes exhibit complete terminal site selectivity in reactions with dienophiles and computational investigations reveal that two discrete pi-conjugative interactions are the origin of this unexpected reactivity. B3LYP/6-31G(d) transition structures also allow an explanation of unexpectedly high pi-diastereofacial selectivities witnessed during these transformations, through the identification of preferred C1-C diene conformations and nonbonded interactions. These new experimental and computational findings encourage the use of linear conjugated polyenes in domino sequences.


Why are not all chilies hot? A trade-off limits pungency.
Evolutionary biologists increasingly recognize that evolution can be constrained by trade-offs, yet our understanding of how and when such constraints are manifested and whether they restrict adaptive divergence in populations remains limited. Here, we show that spatial heterogeneity in moisture maintains a polymorphism for pungency (heat) among natural populations of wild chilies (Capsicum chacoense) because traits influencing water-use efficiency are functionally integrated with traits controlling pungency (the production of capsaicinoids). Pungent and non-pungent chilies occur along a cline in moisture that spans their native range in Bolivia, and the proportion of pungent plants in populations increases with greater moisture availability. In high moisture environments, pungency is beneficial because capsaicinoids protect the fruit from pathogenic fungi, and is not costly because pungent and non-pungent chilies grown in well-watered conditions produce equal numbers of seeds. In low moisture environments, pungency is less beneficial as the risk of fungal infection is lower, and carries a significant cost because, under drought stress, seed production in pungent chilies is reduced by 50 per cent relative to non-pungent plants grown in identical conditions. This large difference in seed production under water-stressed (WS) conditions explains the existence of populations dominated by non-pungent plants, and appears to result from a genetic correlation between pungency and stomatal density: non-pungent plants, segregating from intra-population crosses, exhibit significantly lower stomatal density (p = 0.003), thereby reducing gas exchange under WS conditions. These results demonstrate the importance of trait integration in constraining adaptive divergence among populations.


Two Notorious Nodes: a Critical Examination of Relaxed Molecular Clock Age Estimates of the Bilaterian Animals and Placental Mammals.
The popularity of relaxed clock Bayesian inference of clade origin timings has generated several recent publications with focal results considerably older than the fossils of the clades in question. Here we critically examine two such clades: the animals (with focus on the bilaterians); and the mammals (with focus on the placentals). Each example displays a set of characteristic pathologies which, although much commented on, are rarely corrected for. We conclude that in neither case does the molecular clock analysis provide any evidence for an origin of the clade deeper than what is suggested by the fossil record. In addition, both these clades have other features (including, in the case of the placental mammals, proximity to a large mass extinction) that allow us to generate precise expectations of the timings of their origins. Thus, in these instances the fossil record can provide a powerful test of molecular clock methodology, and why it goes astray; and we have every reason to think these problems are general.


Human Albumin Use in Adults in U.S. Academic Medical Centers.
To determine rates and predictors of albumin administration, and estimated costs in hospitalized adults in the United States. Cohort study of adult patients from the University HealthSystem Consortium database from 2009 to 2013. One hundred twenty academic medical centers and 299 affiliated hospitals. A total of 12,366,264 hospitalization records. Analysis of rates and predictors of albumin administration, and estimated costs. Overall the proportion of admissions during which albumin was administered increased from 6.2% in 2009 to 7.5% in 2013; absolute difference 1.3% (95% CI, 1.30-1.40%; p < 0.0001). The increase was greater in surgical patients from 11.7% in 2009 to 15.1% in 2013; absolute difference 3.4% (95% CI, 3.26-3.46%; p < 0.0001). Albumin use varied geographically being lowest with no increase in hospitals in the North Eastern United States (4.9% in 2009 and 5.3% in 2013) and was more common in bigger (> 750 beds; 5.2% in 2009 and 7.3% in 2013) compared to smaller hospitals (< 250 beds; 4.4% in 2009 to 6.2% in 2013). Factors independently associated with albumin use were appropriate indication for albumin use (odds ratio, 65.220; 95% CI, 62.459-68.103); surgical admission (odds ratio, 7.942; 95% CI, 7.889-7.995); and high severity of illness (odds ratio, 8.933; 95% CI, 8.825-9.042). Total estimated albumin cost significantly increased from $325 million in 2009 to $468 million in 2013; (absolute increase of $233 million), p value less than 0.0001. The proportion of hospitalized adults in the United States receiving albumin has increased, with marked, and currently unexplained, geographic variability and variability by hospital size.


[Analysis of the frequency of experimentation with and consumption of drugs in high-school students].
The aim of this study was to survey the frequency of experimentation and consumption of drugs in high-school students in Cordoba, Argentina, relating it to socio-demographic variables. An observational-analytical method was employed, on the basis of the records of the Secretary for the Planning of Drug-Addiction Prevention and Fighting of Drug-Trafficking. Statistical. Bivariate analysis, odds ratio and confidence interval were applied in the processing of each variable. Alcohol consumption was found to be more frequent among males. Of the subjects 12.2% had tried some type of illicit substance. Tranquilizers were the most commonly used psycho-medicine. Drug consumption increased with age, years of schooling and availability of money. Our detection of an epidemiological situation is deemed useful for prevention strategies for drug addiction among teenagers.


Helicobacter pylori infection and the risk of acute coronary syndrome: a nationwide retrospective cohort study.
Helicobacter pylori infection (HPI) imposes substantial social costs and is of major etiological importance in peptic ulcer disease, gastric cancer, and accelerated cardiovascular diseases. This study determined the risk of acute coronary syndrome (ACS) associated with HPI in a nationwide retrospective cohort study. By using the Taiwan National Health Insurance Research Database (NHIRD), we identified patients diagnosed with HPI from 1998 to 2010. In addition, we randomly selected non-HPI controls frequency-matched by age, sex, and index year from the general population free of HPI. The risk of ACS was analyzed using Cox proportional hazards regression models in which sex, age, and comorbidities were included as variables. We identified 17,075 participants for the HPI group and selected 68,300 participants for the comparison group. The incidence rates were increased in the patients in the HPI group compared with those in the comparison group. Overall, the HPI patients exhibited a 1.93-fold high crude hazard ratio for ACS, and a 1.48-fold adjusted hazard ratio after age, sex, and comorbidities were adjusted. However, the overall adjusted hazard ratio of ACS increased with increasing age with a 3.11 to 8.24 adjusted hazard ratio among the various age groups. Several comorbidities, such as diabetes, hyperlipidemia, and COPD exhibited synergistic effects for ACS risk. We determined a significant association between ACS and comorbidities and provide evidence to encourage clinicians to observe ACS-related comorbidities.


The Current State of Beta-Cell-Mass PET Imaging for Diabetes Research and Therapies.
Diabetes is a chronic metabolic disease affecting over 400 million people worldwide and one of the leading causes of death, especially in developing nations. The disease is characterized by chronic hyperglycemia, caused by defects in the insulin secretion or action pathway. Current diagnostic methods measure metabolic byproducts of the disease such as glucose level, glycated hemoglobin (HbA1c), insulin or C-peptide levels, which are indicators of the beta-cell function. However, they inaccurately reflect the disease progression and provide poor longitudinal information. Beta-cell mass has been suggested as an alternative approach to study disease progression in correlation to beta-cell function, as it behaves differently in the diabetes physiopathology. Study of the beta-cell mass, however, requires highly invasive and potentially harmful procedures such as pancreatic biopsies, making diagnosis and monitoring of the disease tedious. Nuclear medical imaging techniques using radiation emitting tracers have been suggested as strong non-invasive tools for beta-cell mass. A highly sensitive and high-resolution technique, such as positron emission tomography, provides an ideal solution for the visualization of beta-cell mass, which is particularly essential for better characterization of a disease such as diabetes, and for estimating treatment effects towards regeneration of the beta-cell mass. Development of novel, validated biomarkers that are aimed at beta-cell mass imaging are thus highly necessary and would contribute to invaluable breakthroughs in the field of diabetes research and therapies. This review aims to describe the various biomarkers and radioactive probes currently available for positron emission tomography imaging of beta-cell mass, as well as highlight the need for precise quantification and visualization of the beta-cell mass for designing new therapy strategies and monitoring changes in the beta-cell mass during the progression of diabetes.


Osteoporosis in men with idiopathic hypogonadotropic hypogonadism.
To assess the effect of testosterone deficiency on skeletal integrity in men, we determined bone density in 23 hypogonadal men with isolated gonadotropin-releasing hormone deficiency and compared those values with ones from controls. Cortical bone density, as assessed by single-photon absorptiometry of the nondominant radius, ranged from 0.57 to 0.86 g/cm2 (mean +/- SE, 0.71 +/- 0.02) in patients with fused epiphyses and from 0.57 to 0.67 g/cm2 (mean, 0.61 +/- 0.01) in patients with open epiphyses, both of which were significantly (p less than 0.001) lower than normal. Spinal trabecular bone density, as assessed by computed tomography, was similarly decreased (p less than 0.0001) and ranged from 42 to 177 mg K2HPO4/cm3 (mean, 112 +/- 7). Cortical bone density was at least 2 SD below normal in 16 of 23 men, and 8 men had spinal bone densities below the fracture threshold of 80 to 100 mg K2HPO4/cm3. Osteopenia was equally severe in men with immature and mature bone ages, suggesting that abnormal bone development plays an important role in the osteopenia of men with idiopathic hypogonadotropic hypogonadism.


European survey of diagnosis and management of the polycystic ovary syndrome: results of the ESE PCOS Special Interest Group's Questionnaire.
There is evidence for differences between endocrinologists and other specialists in their approach to diagnosis and management of the polycystic ovary syndrome (PCOS). A mailed survey consisting of a simple questionnaire aiming to understand current practice for diagnosis and management of the PCOS by specialists across Europe. The questionnaire consisted of 23 questions grouped to achieve information on i) the general characteristics of the respondents, ii) patients with PCOS seen by endocrinologists, iii) the main diagnostic criteria, iv) biochemical parameters used in the differential diagnosis of hyperandrogenism, v) long-term concerns, and, finally vi) treatment choices. A total of 357 questionnaires representing 13.3% of the members of European Society of Endocrinology (ESE) were available for final analysis; 93% of the respondents were endocrinologists In relation to the diagnostic criteria, respondents were most likely to select menstrual irregularity as the most frequent criteria used for the diagnosis of PCOS although very high rates were achieved for the use of hirsutism and biochemical hyperandrogenism. It therefore appears that the NIH criteria were followed by the majority of respondents. The most frequent biochemical parameters in the differential diagnosis of hyperandrogenism were total testosterone or free androgen index. Obesity and type 2 diabetes were regarded as the principal long-term concerns for PCOS. The most common treatments for patients with PCOS were metformin (33%), lifestyle modification (25%), and oral contraceptives (22%). More direct treatments of infertility include clomiphene citrate alone or in combination with metformin, prescribed by 9 and 23%, respectively, whereas only 6% used other methods for induction of ovulation. The survey produced by ESE is a good start for evaluating the perspective in the diagnosis and treatment of PCOS by endocrinologists in Europe.


Changes in kinetics of carnitine palmitoyltransferase in liver and skeletal muscle of dogs (Canis familiaris) throughout growth and development.
This study was conducted to investigate developmental changes in the kinetics of carnitine palmitoyltransferase (CPT) within hepatic and skeletal muscle tissues of the canine species. Carnitine concentrations, CPT activity and the apparent K(m) for carnitine were measured in tissue homogenates from dogs in six age categories: newborn; 24-h-old; 3-, 6- and 9-wk-old; and adult. Hepatic CPT activity was low at birth, increased by 100% during the suckling period (P < 0.05) and then declined after weaning to adult levels. In contrast, CPT activity in muscle continued to increase with age, reaching adult levels after 9 wk. Congruent with CPT activity, nearly identical concentration profiles of liver and muscle acylcarnitines were observed. The apparent K(m) of hepatic CPT for carnitine also paralleled the increase in CPT activity during the suckling period; however, free and total liver carnitine concentrations declined by 50% during this time (P < 0.05). Beginning at 3 wk of age, the hepatic concentration of free carnitine was at or below the apparent K(m) of CPT for carnitine. A similar relationship existed in muscle of young dogs, but in adults, the free carnitine concentration was markedly increased and exceeded the apparent K(m) by 5-fold. Collectively, we infer that fatty acid oxidation capacity increases rapidly after birth in the canine, after ontogenic increases in CPT activity. Furthermore, based on the relatively low tissue carnitine concentrations when compared with the apparent carnitine K(m) of CPT, we suggest that carnitine may have an important role in the regulation of fatty acid oxidation and that increased dietary carnitine may improve fatty acid oxidative capacity in developing dogs.


A single-blind study of 'as-needed' ecopipam for gambling disorder.
Gambling disorder is a disabling illness experienced by 1% to 3% of adults. Pharmacologic management of gambling disorder has produced mixed results, with some but not all studies showing medication to be more effective than placebo. Ecopipam may offer promise for treating gambling disorder because of its antagonism of dopamine-1 receptors. Twenty-eight individuals with gambling disorder were enrolled and received ≥1 dose of oral ecopipam in an 8-week trial (1 week placebo lead-in, 6 weeks of medication (50 to 100 mg/d as needed), and 1 week follow-up. Participants were enrolled between September 2010 and June 2011 at 3 sites in the United States. Change from baseline to study endpoint on the Yale-Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) was the primary outcome measure. Treatment was associated with statistically significant reductions in the PG-YBOCS total score (baseline score of 25.6 reduced to 14.0 at study endpoint; P>.001) and PG-YBOCS subscales (Thought-Urge and Behavior, P>.001). These findings suggest that pharmacologic targeting of the dopamine-1 receptor may be beneficial in gambling behavior. Placebo-controlled, double-blind studies are warranted to confirm these preliminary findings.


Comparative analysis of deep learning methods for lesion detection on full screening mammography.
Breast cancer is the most prevalent type of cancer in women. Although mammography is used as the main imaging modality for the diagnosis, robust lesion detection in mammography images is a challenging task, due to the poor contrast of the lesion boundaries and the widely diverse sizes and shapes of the lesions. Deep Learning techniques have been explored to facilitate automatic diagnosis and have produced outstanding outcomes when used for different medical challenges. This study provides a benchmark for breast lesion detection in mammography images. Five state-of-art methods were evaluated on 1592 mammograms from a publicly available dataset (CBIS-DDSM) and compared considering the following seven metrics: i) mean Average Precision (mAP); ii) intersection over union; iii) precision; iv) recall; v) True Positive Rate (TPR); and vi) false positive per image. The CenterNet, YOLOv5, Faster-R-CNN, EfficientDet, and RetinaNet architectures were trained with a combination of the L1 localization loss and L2 localization loss. Despite all evaluated networks having mAP ratings greater than 60%, two managed to stand out among the evaluated networks. In general, the results demonstrate the efficiency of the model CenterNet with Hourglass-104 as its backbone and the model YOLOv5, achieving mAP scores of 70.71% and 69.36%, and TPR scores of 96.10% and 92.19%, respectively, outperforming the state-of-the-art models.Clinical Relevance - This study demonstrates the effectiveness of deep learning algorithms for breast lesion detection in mammography, potentially improving the accuracy and efficiency of breast cancer diagnosis.


Complications of internally fixed femoral neck fractures.
Femoral neck fractures in young patients are the emergent injuries that require precise reduction and stable fixation. Despite all advances, nonunion and avascular necrosis (AVN) of the femoral head are the major complications necessitating salvage procedures. In this retrospective series, we evaluated the complications of internally fixed femoral neck fractures. This study consisted of 32 cases that had displaced femoral neck fractures. Although some of them admitted to hospital more than 8 hours after initial trauma, all underwent internal fixation as early as possible. All the fractures were reduced and fixed by closed reduction under fluoroscopy control. However, 5 cases needed open reduction. AVN was determined by using Ficat and Arlet criteria. Clinical evaluation was performed based on the scoring system described by Harris. Mean follow-up period was 49+/-29 months (range 24-126). AVN of the femoral head was observed in 13 cases (40%). However, only 5 of them had unsatisfactory clinical results requiring salvage surgery as total hip replacement. Nonunion of fracture was seen in 5 cases. In the statistical analysis, a negative correlation was observed between the degree of AVN and clinical findings. We found no correlation between the duration of the preoperative period and late complications. AVN is the most common complication of displaced femoral neck fractures. However, less than half of these cases require salvage procedures. Total hip replacement is the preferred treatment option for these cases.


Combined endoscopy-assisted cranionasal approach for resection of infantile myofibromatosis of the ethmoid and anterior skull base. Case report.
The advent and widespread development of endonasal endoscopic techniques have recently expanded the frontiers of skull base surgery. The reduced invasiveness, wider and adjustable visualization of the operative field, and lack of postoperative cosmetic defects are well-known advantages of the endonasal endoscopic approaches compared with traditional surgical exposures both in adults and in children. The need to avoid disruption of facial growth centers and permanent tooth roots represents a further special consideration in favor of these endoscopic techniques in children. The authors report on a case of solitary myofibroma involving the ethmoid, mesial orbits, and anterior skull base with intracranial intradural expansion in a 17-month-old girl. The occurrence of such proliferative disease along the skull base is exceedingly rare. The tumor was successfully excised via an endoscopy-assisted cranionasal approach in which a transcranial microsurgical exposure was combined with endonasal endoscopic access to ensure a radical resection and optimize skull base reconstruction. To the authors' knowledge, the patient in this case is the youngest reported patient in the literature who has undergone treatment with this surgical strategy. The outcome in this patient underscores the feasibility and safety of endoscopic endonasal surgery even in toddlers and early childhood.


Technical adequacy of fluoroscopic spot films of the gastrointestinal tract: comparison of residents and technologists.
We compared images obtained during gastrointestinal fluoroscopy by specially trained and experienced technologists with those obtained by radiology residents to determine if the quality of images was similar between the two groups. Three senior radiologists examined the fluoroscopic spot films of 80 patients who were divided evenly into four groups: barium enemas performed by technologists, barium enemas performed by residents, gastrointestinal series performed by technologists, and gastrointestinal series performed by residents. The senior radiologists graded adequacy of visualization of the esophagus, stomach, duodenum, and all parts of the colon. A grade of 1 was given for poor films, 2 for adequate films, and 3 for good films. They did not know who performed each study. For barium enemas, the residents' mean score was slightly higher than that of the technologists (13.5 compared with 12.9). For gastrointestinal series, residents' mean score was again slightly higher (20.5 compared with 19.7). In neither case did the difference reach statistical significance. Fluoroscopic films obtained by residents and by specially trained and experienced technologists for barium enemas or gastrointestinal series were statistically indistinguishable.


Dimethyl fumarate is efficacious in severe plaque psoriasis : Post hoc analysis from the BRIDGE trial in Austria.
Fumaric acid esters are recommended in European guidelines for induction and maintenance treatment of patients with moderate to severe plaque psoriasis. A systemic medication with pure dimethyl fumarate without monoethyl fumarate salts was recently licensed in Europe. The efficacy and safety of pure dimethyl fumarate were assessed in patients with severe (physician global assessment) plaque psoriasis in Austria in the BRIDGE trial. In this double blind, randomized, placebo-controlled trial patients received 16-week treatment with pure dimethyl fumarate in a head to head comparison with dimethyl fumarate with monoethyl fumarate salts, which is licensed in Germany. In this post hoc analysis the efficacy and safety were assessed in patients with severe psoriasis in Austria. Efficacy measures significantly improved in both active treatment arms compared to placebo in 65 patients after 16 weeks of treatment. Physician global assessment of clear/almost clear in the dimethyl fumarate group was non-inferior to the dimethyl fumarate with monoethyl fumarate salts group 2 months after end of treatment. No serious adverse reaction occurred in patients with dimethyl fumarate in contrast to the second active treatment. Efficacy outcome was paralleled by quality of life improvements. This is the first report of dimethyl fumarate in a severely affected population with plaque psoriasis. Dimethyl fumarate is effective and safe in the systemic treatment of adults with severe psoriasis (physician global assessment).


Diurnal variations of neurocardiac rhythms in acute myocardial infarction.
To determine the diurnal pattern of cardiac autonomic tone in acute myocardial infarction (AMI), this study examined the power spectrum of heart rate (HR) variability in 24 patients during a single 24-hour segment within 4 days of AMI. Patients were nonrandomly allocated to a group (n = 14) without autonomic drugs and to a group (n = 10) already receiving beta blockers at the time of AMI. With use of autoregressive modeling, the power spectrum of HR variability was computed from continuous 1-hour electrocardiographic segments recorded at equally spaced intervals; 7 to 8 A.M., 3 to 4 P.M., and 11 to 12 P.M. All patients were supine, awake and pain free during recordings. There were no differences in HR, HR variance or the low-frequency peak power (0.06 to 0.1 Hz) from one temporal sequence to another. For the patients not taking beta blockers, the high-frequency peak power (0.2 to 0.36 Hz) or vagal component increased significantly from 3 P.M. to 11 P.M. (28 +/- 11 to 45 +/- 20 beats/min2.Hz-1, p less than 0.01). There was a significant decrease in the low- to high-frequency peak power and area ratios from 3 P.M. to 11 P.M. All power spectral parameters in the patients taking beta blockers remained unchanged over 24 hours. There was significantly heightened vagal modulation of sinus node activity in those receiving beta blockers, especially at 7 A.M. and 3 P.M. The data suggest that under steady-state wakeful conditions in the early recovery phase after an AMI, vagal tone is more pronounced during the late evening hours with a possible shift to relative sympathetic dominance during early morning and midafternoon hours.(ABSTRACT TRUNCATED AT 250 WORDS)


The educational value of grand rounds.
There is little recent factual data published relating to the effectiveness of grand rounds as a forum for teaching and learning. This study, undertaken to evaluate the educational value of grand rounds at the Auckland Hospital showed that when required to answer a questionnaire based on medical information transmitted at the previous week's grand round, members of the audience who had been present scored significantly higher than those who were absent. (Possible score 16; score for those present was 12.1, those absent 3.9, p less than 0.001.) However, it was also shown that some in the audience had acquired erroneous information, and although the problem was not a large one, it is recommended that chairmen of grand rounds learn to recognise the potential for confusion when experts speak imprecisely or disagree over points of patient management.


β1-blocker in sepsis.
The use of ultrashort-acting β1-blockers recently has attracted attention in septic patients with non-compensatory tachycardia. We summarized the metabolic and hemodynamic effects and the clinical evidence of ultrashort-acting β1-blockers. A recent meta-analysis showed that ultrashort-acting β1-blockers reduced the mortality in septic patients with persistent tachycardia. However, its mechanism to improve mortality is not fully understood yet. We often use lactate as a marker of oxygen delivery, but an impaired oxygen use rather than reduced oxygen delivery has been recently proposed as a more reasonable explanation of hyperlactatemia in patients with sepsis, leading to a question of whether β1-blockers affect metabolic systems. While the stimulation of the β2-receptor accelerates glycolysis and lactate production, the role of β1-blocker in lactate production remains unclear and studies investigating the role of β1-blockers in lactate kinetics are warranted. A meta-analysis also reported that ultrashort-acting β1-blockers increased stroke volume index, while it reduced heart rate, resulting in unchanged cardiac index, mean arterial pressure, and norepinephrine requirement at 24 h, leading to an improvement of cardiovascular efficiency. On the other hand, a recent study reported that heart rate reduction using fast esmolol titration in the very early phase of septic shock caused hemodynamic instability, suggesting that ultrashort-acting β1-blockers should be started only after completing initial resuscitation. While many clinicians still do not feel comfortable controlling sinus tachycardia, one randomized controlled trial in which the majority had sinus tachycardia suggested the mortality benefit of ultrashort-acting β1-blockers. Therefore, it still deems to be reasonable to control sinus tachycardia with ultrashort-acting β1-blockers after completing initial resuscitation. Accumulating evidence is supporting the use of ultrashort-acting β1-blockers while larger randomized controlled trials to clarify the effect of ultrashort-acting β1-blockers are still warranted.


Is Autophagy a Prerequisite for Steroidogenesis in Leydig Cells?
We investigated the involvement of autophagy with steroidogenesis in testicular Leydig cells. Human chorionic gonadotropin (hCG)-stimulated T production in Leydig cells was not remarkably altered in the presence of an autophagy inhibitor 3-methyladenine (3-MA). Although pretreatment with 3-MA demonstrated a tendency to decrease hCG-induced T production, the differences were significant only at a higher time point of 24 h following hCG. Microtubule associated protein light chain 3 (LC3)-II was detectable in the control cells in all the experiments. The hCG-induced increase in steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleave (P450scc) protein levels were not significantly altered by 3-MA. Leydig cells isolated from immature rat testes 12 h following hCG treatment showed relatively increased levels of LC3-II protein compared to the control group. Furthermore, LC3-II levels shown in these cells reached almost the identical to those from normal adult testes. However, LC3-II protein levels were almost comparable or even slightly lower than the controls at 48 h following hCG. Expression of StAR and P450scc was upregulated at both 12 and 48 h after hCG. We also used MA-10 cells, the mouse Leydig cell line, in this experiment. When dibutyryl cyclic-AMP was treated with MA-10 cells, P4 levels were significantly increased in the cell culture medium. However, P4 levels tended to decrease in the presence of 3-MA, but the difference was not statistically significant. This was consistent with the results of the rat Leydig cell experiments. Together, we believe that although autophagy participates in steroidogenesis and enhances steroidogenic efficacy of Leydig cells, it may not be a decisive cellular process for steroidogenesis, specifically in the mature Leydig cells.


Voice problems in entertainers.
The medical care of entertainers is an art as well as a science; it demands both clinical experience and empathy-an appreciation of the special problems facing the performer. The expansion of our diagnostic acumen with audiovisual equipment and function studies, the addition of new medications and the development of microsurgery and laser surgery have improved the care of the professional voice user. Preventing voice problems by vocal hygiene remains the principal challenge.


Factors Influencing Acceptance of Personal Health Record Apps for Workplace Health Promotion: Cross-Sectional Questionnaire Study.
Health care technologies can help improve workers' health and productivity by supporting workplace health promotion. A personal health record app is used to manage medical data such as results from medical checkups, which facilitates decision making for medical personnel. However, an analysis of users' technology acceptance is required to provide appropriate services based on personal health record apps. The purpose of this study was to analyze the factors influencing the behavioral intention of health experts and workers to use an app in workers' health centers and to examine differences in their perception of the main variables. The study involved health experts and workers who visited 21 workers' health centers in Korea to verify a research model in which perceived risk was added to the unified theory of acceptance and use of technology, a representative theory of information technology acceptance. After receiving ethical approval from the Korea National Institute for Bioethics Policy, 1050 questionnaires were distributed over 7 weeks with cooperation of the Korea Occupational Safety and Health Agency. A multiple linear regression analysis and multigroup path analysis were performed to verify the hypotheses, and independent samples t tests were performed to analyze differences between workers' and health experts' perception of the main variables. The analysis included data from 866 respondents (687 workers and 179 health experts). Effort expectancy (beta=.08, P=.03), social influence (beta=.43, P<.001), performance expectancy (beta=.07, P=.008), and facilitating conditions (beta=.13, P<.001) exerted significant positive effects on behavioral intention, whereas perceived risk (beta=-.29, P<.001) exerted a significant negative effect on behavioral intention. Performance expectancy had a significant effect on path differences depending on gender (critical ratio=-3.38) and age (critical ratio=1.97). Workers' mean scores for the main variables were higher relative to those of health experts for all remaining variables except perceived risk, and significant differences were observed for all remaining variables except facilitating condition. Social influence exerted the strongest effect on behavioral intention to use the personal health record app. Consequently, it is necessary to coordinate health promotion activities in the workplace as well as the operational direction of community institutions such as in workers' health centers to allow workers to manage their own health via continuous use of the app. In addition, the app should be developed based on a requirement analysis of the balance between both interest groups in consideration of differences in perspective between consumers and service providers.


Asparaginase-like protein 1 is an independent prognostic marker in primary endometrial cancer, and is frequently lost in metastatic lesions.
Loss of Asparaginase-like protein 1 (ASRGL1) has been suggested as a prognostic biomarker in endometrial carcinoma. Our objective was to validate this in a prospectively collected, independent patient cohort, and evaluate ASRGL1 expression in endometrial carcinoma precursor lesion and metastases. 782 primary endometrial carcinomas, 90 precursor lesions (complex atypical hyperplasia), and 179 metastases (from 87 patients) were evaluated for ASRGL1 expression by immunohistochemistry in relation to clinical and histopathological data. ASRGL1 mRNA level was investigated in 237 primary tumors and related to survival and ASRGL1 protein expression. Low expression of ASRGL1 protein and ASRGL1 mRNA predicted poor disease specific survival (P<0.001). In multivariate survival analyses ASRGL1 had independent prognostic value both in the whole patient cohort (Hazard ratio (HR): 1.53, 95% confidence interval (CI): 1.04-2.26, P=0.031) and within the endometrioid subgroup (HR: 2.64, CI: 1.47-4.74, P=0.001). Low ASRGL1 expression was less frequent in patients with low grade endometrioid primary tumors compared to high grade endometrioid and non-endometrioid primary tumors, and ASRGL1 was lost in the majority of metastatic lesions. In a prospective setting ASRGL1 validates as a strong prognostic biomarker in endometrial carcinoma. Loss of ASRGL1 is associated with aggressive disease and poor survival, and is demonstrated for the first time to have independent prognostic value in the entire endometrial carcinoma patient population.


Humans in the Loop: Incorporating Expert and Crowd-Sourced Knowledge for Predictions Using Survey Data.
Survey data sets are often wider than they are long. This high ratio of variables to observations raises concerns about overfitting during prediction, making informed variable selection important. Recent applications in computer science have sought to incorporate human knowledge into machine-learning methods to address these problems. The authors implement such a "human-in-the-loop" approach in the Fragile Families Challenge. The authors use surveys to elicit knowledge from experts and laypeople about the importance of different variables to different outcomes. This strategy offers the option to subset the data before prediction or to incorporate human knowledge as scores in prediction models, or both together. The authors find that human intervention is not obviously helpful. Human-informed subsetting reduces predictive performance, and considered alone, approaches incorporating scores perform marginally worse than approaches that do not. However, incorporating human knowledge may still improve predictive performance, and future research should consider new ways of doing so.


Diabetes During the Fasting Month of Ramadan: Is Telemedicine as Efficient as Conventional Follow-Up? Results from a Moroccan Comparative Study.
During the COVID-19 pandemic, access to health care was affected by the lockdown period. To overcome this situation, telemedicine is an alternative to conventional follow-up for patients with diabetes during the fasting month of Ramadan. The aim of this study is to compare the effectiveness of telemedicine consultation of diabetic patients during Ramadan compared with conventional follow-up. This comparative cross-sectional study conducted in the Sheikh Khalifa Ibn Zaid Hospital of Casablanca, Morocco, included diabetic patients followed up by conventional consultation in 2019 Ramadan and by telemedicine in 2020 Ramadan. For each patient and in both Ramadans (2019 and 2020), we have conducted a pre-Ramadan assessment, screening for acute diabetic complications during Ramadan and an evaluation of weight and glycated hemoglobin of patients, after Ramadan. We compared the occurrence of acute complications and the variation of metabolic parameters of patients in Ramadan 2020 with their results in Ramadan 2019. In this study, we included 61 patients. In Ramadan 2020, compared with Ramadan 2019, there was no significant difference in terms of hypoglycemia (18.03% versus 32.78%, p = 0.09), minor hyperglycemia (13.1% versus 11.47%, p = 0.35) and major hyperglycemia or ketoacidosis (3.27% versus 6.55%, p = 0.19). Fasting was interrupted in 8.19% versus 11.47% (p = 0.012). There were no significant variations of weight (+0.62 versus -0.77; p = 0.09). In term of variation of glycated hemoglobin, there was a significant different between Ramadan 2020 and Ramadan 2019 (-0.36 versus -0.61 in 2019, p<0.05). Despite comparable results in terms of weight change and hypoglycemia, our study showed that telemedicine follow-up in patients with diabetes during Ramadan did not provide as effective glycemic control as conventional monitoring.


The use of biochemical markers of bone remodeling in multiple myeloma: a report of the International Myeloma Working Group.
Lytic bone disease is a frequent complication of multiple myeloma (MM). Lytic lesions rarely heal and X-rays are of limited value in monitoring bone destruction during anti-myeloma or anti-resorptive treatment. Biochemical markers of bone resorption (amino- and carboxy-terminal cross-linking telopeptide of type I collagen (NTX and CTX, respectively) or CTX generated by matrix metalloproteinases (ICTP)) and bone formation provide information on bone dynamics and reflect disease activity in bone. These markers have been investigated as tools for evaluating the extent of bone disease, risk of skeletal morbidity and response to anti-resorptive treatment in MM. Urinary NTX, serum CTX and serum ICTP are elevated in myeloma patients with osteolytic lesions and correlate with advanced disease stage. Furthermore, urinary NTX and serum ICTP correlate with risk for skeletal complications, disease progression and overall survival. Bone markers have also been used for the early diagnosis of bone lesions. This International Myeloma Working Group report summarizes the existing data for the role of bone markers in assessing the extent of MM bone disease and in monitoring bone turnover during anti-myeloma therapies and provides information on novel markers that may be of particular interest in the near future.


HBeAg-positive chronic hepatitis B: why do I treat my patients with pegylated interferon.
Worldwide, chronic hepatitis B virus infection is a major cause of end-stage liver disease and hepatocellular carcinoma. While the past two decades have brought major advances in the availability of treatments to help delay or prevent these outcomes, treatment of chronic hepatitis B remains a serious challenge. With the recent availability of potent new nucleot(s)ide such as entecavir, tenofovir and telbuvidine, I still use pegylated interferon (PEG-IFN)-alpha for the treatment of chronic HBeAg-positive patients. This is based on its relatively higher effectiveness in restoring the host immune control on viral replication, resulting in sustained diseases remission in a proportion of patients, a finite course of therapy and the absence of viral resistance. The two major hindrances to its wide application are its lack of effectiveness in a large proportion of patients and its side-effect profile. The former shortcoming can be circumvented to a certain extent with the use of response predictor models. Recently, based on long-term follow-up study, the better durability of sustained response further enhances the confidence in the use of PEG-IFN-alpha in chronic HBeAg-positive patients.


Chemotherapeutical effects of the herbal medicine Uncaria tomentosa (Willd.) DC.
The use of medicinal plants dates back to the beginning of humanity, and today their application as complementary therapy has been widely disseminated as an alternative to conventional therapy. The medicinal plant named Uncaria tomentosa (Willd.) DC. (known as cat's claw) is a common woody vine of the Amazon forest that has traditionally been used in the treatment of arthritis because of its anti-inflammatory properties. This study aimed to evaluate the cytotoxic, mutagenic, and antimutagenic potentials of this medicinal plant. The biological activities of U. tomentosa were determined on bone marrow cells of Wistar rats that were treated in vivo. For the cytotoxic and mutagenic analyses, aqueous plant extract solutions were administered by gavage (1, 2, or 3 mg/mL) for 24 h (an acute treatment) or 7 days (a subchronic treatment). For the antimutagenic analyses, aqueous plant extract solutions (1 mg/mL) were administered by gavage before (pretreatment), simultaneous to (simultaneous treatment), or after (post-treatment), the administration of cyclophosphamide (1.5 mg/mL). U. tomentosa did not show any cytotoxic or mutagenic effects in any of the cytological or chromosomal analyses. Besides, the antimutagenic tests showed that the plant extracts displayed antimutagenic activities, which significantly reduced the percentages of the chromosomal aberrations that were induced by cyclophosphamide at 53.91, 58.60, and 57.03%, respectively, for the simultaneous treatment, pretreatment, and post-treatment. The results suggested a safe use of this herbal medicine that is available free of charge from the Brazilian Public Health System for the treatment of arthritis. This medicinal plant can also effectively contribute to improving the quality of life and the recovery of people undergoing chemotherapeutical treatments.


Exogenous vasotocin alters aggression during agonistic exchanges in male Amargosa River pupfish (Cyprinodon nevadensis amargosae).
Pupfishes in the Death Valley region have rapidly differentiated in social behaviors since their isolation in a series of desert streams, springs, and marshes less than 20,000 years ago. These habitats can show dramatic fluctuations in ecological conditions, and pupfish must cope with the changes by plastic physiological and behavioral responses. Recently, we showed differences among some Death Valley populations in brain expression of arginine vasotocin (AVT). As AVT regulates both hydromineral balance and social behaviors in other taxa, these population differences may indicate adaptive changes in osmoregulatory and/or behavioral processes. To test whether AVT is relevant for behavioral shifts in these fish, here we examined how manipulations to the AVT system affect agonistic and reproductive behaviors in Amargosa River pupfish (Cyprinodon nevadensis amargosae). We administered exogenous AVT (0.1, 1, and 10 microg/g body weight) and an AVP V1 receptor antagonist (Manning compound, 2.5 microg/g body weight) intraperitoneally to males in mixed-sex groups in the laboratory. We found that AVT reduced the initiation of aggressive social interactions with other pupfish but had no effect on courtship. The effects of AVT were confirmed in males in the wild where AVT (1 microg/g body weight) reduced the aggressive initiation of social interactions and decreased aggressive responses to the behavior of other males. Combined, these results show that AVT can modulate agonistic behaviors in male pupfish and support the idea that variation in AVT activity may underlie differences in aggression among Death Valley populations.


Three-dimensional printing of intracardiac defects from three-dimensional echocardiographic images: feasibility and relative accuracy.
With the advent of three-dimensional (3D) printers and high-resolution cardiac imaging, rapid prototype constructions of congenital cardiac defects are now possible. Typically, source images for these models derive from higher resolution, cross-sectional cardiac imaging, such as cardiac magnetic resonance imaging or computed tomography. These imaging methods may involve intravenous contrast, sedation, and ionizing radiation. New echocardiographic transducers and advanced software and hardware have optimized 3D echocardiographic images for this purpose. Thus, the objectives of this study were to confirm the feasibility of creating cardiac models from 3D echocardiographic data and to assess accuracy by comparing 3D model measurements with conventional two-dimensional (2D) echocardiographic measurements of cardiac defects. Nine patients undergoing 3D echocardiography were identified (eight with ventricular septal defects, one with three periprosthetic aortic valve leaks). Raw echocardiographic image data were exported anonymously and converted to Digital Imaging and Communications in Medicine format. The image data were filtered for noise reduction, imported into segmentation software to create a 3D digital model, and printed. Measurements of the defects from the 3D model were compared with defect measurements from conventional 2D echocardiographic data. Meticulous care was taken to ensure identical measurement planes. Long- and short-axis measurements of eight ventricular septal defects and three perivalvar leaks were obtained. Mean ± SD values for the 3D model measurements and conventional 2D echocardiographic measurements were 7.5 ± 6.3 and 7.1 ± 6.2 mm respectively (P = .20), indicating no significant differences between the standard 2D and 3D model measurements. The two groups were highly correlated, with a Pearson correlation coefficient of 0.988. The mean absolute error (2D - 3D) for each measurement was 0.4 ± 0.9 mm, indicating accuracy of the 3D model of <1 mm. Three-dimensional printed models of echocardiographic data are technically feasible and may accurately reflect ventricular septal defect anatomy. Three-dimensional models derived from 3D echocardiographic data sets represent a new tool in procedural planning for children with congenital heart disease.


Corticomuscular coherence reflects somatosensory feedback gains during motor adaptation.
Beta-band corticomuscular coherence (CMC) observed between the sensorimotor cortex activity and contracting muscle is declaratively described as a neurophysiological reflection of sensorimotor binding. However, much remains unknown about the functional meaning of 'sensorimotor binding.' The efficacy of information binding in the sensorimotor system is assumed to be influenced by the gain of the feedback controller, which is regulated through a process that may in part be implemented in the primary sensorimotor cortex (SM1). Thus, we predicted that CMC is modulated together with feedback gains during motor learning. We examined this hypothesis using a hand-reaching adaptation task under a novel dynamical environment. CMC modulation was assessed before and after adaptation, and feedback gains were probed by long latency triggered muscle reactions. Overall, we found that CMC significantly decreased during the adaptation period, and such CMC decrease was associated with the decreased long latency reflexes. These results suggest that CMC has a related function to modulation of feedback gains. Our findings provided an electrophysiological hallmark of the sensorimotor binding process, which was stated as a function of CMC but poorly understood.


Numerical analysis of the performance of Mach-Zehnder interferometric logic gates enhanced with coupled nonlinear ring- resonators.
In this paper, the implementation of an all-optical logic gate based on a Mach-Zehnder interferometer (MZI) configuration is addressed with underlying nonlinear slot-waveguides. In order to reduce power consumption requirements, different ring-resonator structures are introduced in the arms of the MZI. A nonlinear Transfer Matrix Method is developed and used to analyze the response of the nonlinear MZI in order to optimize power requirements with maximum bit rates. The numerical analysis shows that a reduction in the switching power from 2.5 W to less than 5 mW can be achieved by a proper design of the ring-resonator structures introduced in the MZI arms. In addition, it is shown that the logic gate can handle bit rates higher than 60 Gbit/s.


Effect of sildenafil citrate on the male sexual experience assessed with the Sexual Experience Questionnaire: a multicenter, double-blind, placebo-controlled trial with open-label extension.
The Sexual Experience Questionnaire (SEX-Q) enables quick and easy assessment of functional, emotional, and satisfaction-related aspects of the sexual experience in men with erectile dysfunction (ED). To assess correlations between improvement on the SEX-Q and outcomes on other validated questionnaires. METHODS. Men with ED (score < or =25 on the Erectile Function domain of the International Index of Erectile Function [IIEF]) who had used less than or equal to six doses of any phosphodiesterase 5 inhibitor (none within 6 months) were randomized to 10 weeks of double-blind, placebo-controlled (DBPC) flexible-dose sildenafil citrate (50 or 100 mg, as needed), followed by 6 weeks of open-label (OL) sildenafil. SEX-Q, IIEF, Quality of Erection Questionnaire (QEQ), Self-Esteem and Relationship (SEAR) Questionnaire, Erection Hardness Score (EHS), successful intercourse attempts (SIAs), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and global efficacy questions (GEQs). Compared with the placebo group (N = 105), the sildenafil group (N = 104) at DBPC end of treatment (EOT) had significantly more improvement (P < 0.05) on all SEX-Q, IIEF (except the Sexual Desire domain), QEQ, and SEAR outcomes, more frequent SIAs and EHS 3 (hard enough for penetration but not completely hard) or EHS 4 (completely hard) erections (odds ratio [OR], 2.52 and 3.46, respectively), EHS 4 erections four times as often (OR, 6.41), more men satisfied with treatment (EDITS; OR, 2.6), approximately twice as many men with improved erections (GEQ1; OR, 5.8) and ability to have sexual intercourse (GEQ2; OR, 5.4), and GEQ3 scores that indicated better sex (P < 0.0001). SEX-Q score improvements correlated positively with all other outcomes. At OL EOT, most outcomes were >60% (and approximately half were > or =80%) of the maximum positive result. SEX-Q change scores correlate with several other functional, emotional, and satisfaction-related outcomes in men treated with sildenafil for ED, allowing a simple and focused evaluation of the sexual experience.


Positive Parenting Behaviors: Impact on the Early Vocabulary of Infants/Toddlers With Cochlear Implants.
Purpose To extend our knowledge about factors influencing early vocabulary development for infants with cochlear implants (CIs), we investigated the impact of positive parenting behaviors (PPBs) from the Indicator of Parent Child Interaction, used in parent-child interactions during everyday activities. Method Implantation age for the sample recruited from CI clinics in Australia ranged from 6 to 10 months for 22 children and from 11 to 21 months for 11 children. Three observation sessions at three monthly intervals were coded for use of PPBs. Children's productive vocabulary, based on the MacArthur-Bates Communicative Development Inventories parent checklist, was collected approximately 6 and 9 months later. A repeated-measures negative binomial generalized linear mixed-effects model was used to investigate associations between the total PPBs per session, covariates (maternal education, gender, and time since implant), and the number of words produced. In follow-up analyses with the PPBs entered separately, variable selection was used to retain only those deemed informative, based on the Akaike information criterion. Results As early as Session 1, associations between the PPBs and vocabulary were identified. Time since implant had a positive effect. For different sessions, specific PPBs (descriptive language, follows child's lead, and acceptance and warmth) were identified as important contributors. Conclusions Complementing previous findings, valuable information was identified about parenting behaviors that are likely to impact positively the early vocabulary of infants with CIs. Of importance is providing parents with information and training in skills that have the potential to help create optimal contexts for promoting their child's early vocabulary development.


Fever in term labour.
To determine the antecedents, outcomes, and effects of treatment of fever commencing during term labour without prolonged rupture of membranes (ROM). A retrospective database and chart review sought associations between maternal, fetal, and labour variables and fever by comparing women whose membranes had been ruptured for less than 24 hours and who were febrile with those who were not. The strength of significant associations was then compared between febrile women who received acetaminophen or antibiotics and febrile women who did not. We found 16 322 control subjects and 161 cases. On multivariable analysis, fever was associated with epidural analgesia (adjusted odds ratio [AOR] 5.5; 95% confidence interval [CI], 4.0-7.0), length of stage 2 (AOR 1.003 per minute; 95% CI, 1.001-1.005), length of ROM (AOR 1.15 per hour; 95% CI, 1.10-1.20), meconium in the amniotic fluid (AOR 1.7; 95% CI, 1.2-2.2), intervention for nonreassuring electronic fetal monitoring (EFM) (AOR 5.2; 95% CI, 4.4-6.0), intervention for failure to progress in labour (AOR 3.0; 95% CI, 2.1-3.9), and neonatal intensive care unit (NICU) admission (AOR 5.7; 95% CI, 5.1-6.3). A nonstatistically significant trend toward a decrease in failure to progress with acetaminophen administration was noted. Fever during labour is associated with longer labour, longer ROM, and use of epidural analgesia. For a given length of labour, women with fever are more likely to experience intervention for failure to progress, intervention for nonreassuring EFM, and infant NICU admission.


Abnormal estrogen conjugation in women at risk for familial breast cancer at the periovulatory stage of the menstrual cycle.
The present study was designed to establish whether women with a family history of breast cancer exhibit endocrine abnormalities which could be responsible for their increased risk for the disease. Plasma hormone levels were measured every second day throughout the menstrual cycle in 30 women at risk for familial breast cancer and in an equal number of matched controls. Thirteen of the 14 substances measured exhibited no differences between the two populations, but plasma androsterone sulfate was significantly lower in the high-risk subjects. Thirteen urinary hormones were measured every day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in thry day throughout the cycle with only the mean estrone and estradiol glucuronide but not estriol glucuronide content being significantly lower in the high-risk subjects. A compensatory increase in the urinary estrogen sulfates was observed. Daily analysis of these differences showed that they were most pronounced in the periovulatory period of the cycle. These results suggest that the genetic risk for breast cancer is associated with an abnormality in estrogen conjugation at a specific time of the ovulatory cycle.


New Neandertal wrist bones from El Sidrón, Spain (1994-2009).
Twenty-nine carpal bones of Homo neanderthalensis have been recovered from the site of El Sidrón (Asturias, Spain) during excavations between 1994 and 2009, alongside ∼2500 other Neandertal skeletal elements dated to ∼49,000 years ago. All bones of the wrist are represented, including adult scaphoids (n = 6), lunates (n = 2), triquetra (n = 4), pisiforms (n = 2), trapezia (n = 2), trapezoids (n = 5), capitates (n = 5), and hamates (n = 2), as well as one fragmentary and possibly juvenile scaphoid. Several of these carpals appear to belong to the complete right wrist of a single individual. Here we provide qualitative and quantitative morphological descriptions of these carpals, within a comparative context of other European and Near Eastern Neandertals, early and recent Homo sapiens, and other fossil hominins, including Homo antecessor, Homo naledi, and australopiths. Overall, the El Sidrón carpals show characteristics that typically distinguish Neandertals from H. sapiens, such as a relatively flat first metacarpal facet on the trapezium and a more laterally oriented second metacarpal facet on the capitate. However, there are some distinctive features of the El Sidrón carpals compared with most other Neandertals. For example, the tubercle of the trapezium is small with limited projection, while the scaphoid tubercle and hamate hamulus are among the largest seen in other Neandertals. Furthermore, three of the six adult scaphoids show a distinctive os-centrale portion, while another is a bipartite scaphoid with a truncated tubercle. The high frequency of rare carpal morphologies supports other evidence of a close genetic relationship among the Neandertals found at El Sidrón.


Behavioral and epigenetic consequences of oxytocin treatment at birth.
Oxytocin is used in approximately half of all births in the United States during labor induction and/or augmentation. However, the effects of maternal oxytocin administration on offspring development have not been fully characterized. Here, we used the socially monogamous prairie vole to examine the hypothesis that oxytocin exposure at birth can have long-term developmental consequences. Maternally administered oxytocin increased methylation of the oxytocin receptor (Oxtr) in the fetal brain. As adults, oxytocin-exposed voles were more gregarious, with increased alloparental caregiving toward pups and increased close social contact with other adults. Cross-fostering indicated that these effects were the result of direct action on the offspring, rather than indirect effects via postnatal changes in maternal behavior. Male oxytocin-exposed offspring had increased oxytocin receptor density and expression in the brain as adults. These results show that long-term effects of perinatal oxytocin may be mediated by an epigenetic mechanism.


Effects of oral/enteral nutrition alone versus plus pantoprazole on gastrointestinal bleeding in critically ill patients with low risk factor: a multicenter, randomized controlled trial
Critically ill patients are at risk of developing gastrointestinal (GI) bleeding due to stress causing mucosal damage. Aim of the study was to determine the effect of oral/enteral nutrition with or without concomitant pantoprazole on upper GI bleeding in low risk critically ill patients. This was a prospective, randomized, open-label, multicenter study conducted with intensive care unit (ICU) patients receiving oral/enteral nutritional support. Patients were randomly assigned into two groups including intervention group (received oral/EN plus pantoprazole) and control group (received only oral/EN). A total of 300 patients (intervention group: 152, control group: 148) participated in the study. Overall, 226 (75%) patients were fed by orally and 74 (25%) patients fed by enteral tube feeding. Median duration of nutritional support 4 (range: 2–33) days. Overt upper GI bleeding was noted only in one patient (0.65%) who was in the intervention group. The overall length of ICU stay of 4 (2–105) days, while ICU stay was significantly longer in the intervention group than in the control group (P = 0.006). Our findings seems to indicate that in patients who are at low risk for GI bleeding and under oral/enteral nutritional support, the use of PPIs may not reduce the risk of bleeding, however these results are imprecise because of low event (GI bleeding) rate and limited power.


10-year results following impaction bone grafting of major bone defects in 29 rotational and hinged knee revision arthroplasties: a follow-up of a previous report.
Substantial bone loss in revision total knee arthroplasty (TKA) is a challenging problem. We studied whether impaction bone grafting provides long-term restoration of bone stock in the treatment of major bone defects in revision surgery of rotational and hinged knee arthroplasties (LINK Endo-Model). Between 1996 and 2006, 29 knees in 29 patients underwent revision procedures of rotational and hinged knee arthroplasties using impaction bone grafting (IBG) to reconstruct major bone defects. At the latest follow-up, the clinical examination included the Knee Society score (KSS), standardized radiographs, and a questionnaire for the WOMAC score. After a mean follow-up of 10 (6-13) years, 14 knees with 19 IBG reconstructions (5 total, 9 partial revisions) had failed. 12 knees were treated with re-revision surgery mean 5 (1-12) years after the first revision, due to mechanical failure and aseptic loosening of the components. In all these failed cases, the surgeon observed a lack of incorporation with bone graft resorption in the femur or tibia during the re-revision procedure. In all 15 knees that were not re-revised, with 21 reconstructions (6 total, 9 partial revisions), an improvement in the combined KSS score (knee score + function score) of 60 points (p < 0.001) was found at the latest follow-up. In 12 of these knees, a clear incorporation with no visible radiolucent lines around the component and no sign of substantial graft resorption was noted, while unclear radiographic graft incorporation was seen in 3 knees. Our results clearly indicate that IBG alone is not a methodologically sound technique in the revision of rotational and hinged knee arthroplasties.


Non-linear Relationships Between the Built Environment and Walking Frequency Among Older Adults in Zhongshan, China.
Aim: Promoting walking activity is an effective way to improve the health of older adults. Walking frequency is a critical component of walking behavior and an essential determinant of daily walking levels. To decipher the association between the built environment and walking frequency among older adults, this study's aims are as follows: (1) to empirically test whether non-linear relationships between the two exist, and (2) to identify the thresholds of the built environment characteristics that promote walking. Methods: The walking frequency of old adults was derived from the Zhongshan Household Travel Survey (ZHTS) in 2012. The sample size of old adults aged 60 or over was 4784 from 274 urban and rural neighborhoods. A semi-parametric generalized additive model (GAMM) is used to analyze the non-linear or non-monotonic relationships between the built environment and the walking frequency among older adults. Results: We found that non-linear relationships exist among five out of the six built environment characteristics. Within certain thresholds, the population density, sidewalk density, bus stop density, land use mixture, and the percentage of green space are positively related to older adults' walking trips. Furthermore, the land use mixture and the percentage of green space show an inverse "V"-shaped relationship. Conclusions: Built environment features can either support or hinder the walking frequency among older adults. The findings in the current study contribute to effective land use and transport policies for promoting active travel among older adults.


Postural displacement of the brain: feasibility of using CT for determination of stereotaxic coordinates.
Ten patients were studied with computed tomography (CT) in an attempt to determine if CT could be used preoperatively to establish stereotaxic coordinates for an operation and to find out more about how postural changes affect the position of the brain. Certain well defined cerebral structures were chosen as anatomic landmarks, and their relation to the skull determined with the patient in the supine, lateral, and prone positions. An external helmet fixation system was used to ensure consistent and reproducible CT slices. No displacement of the brain structures was observed in any of the positions, so it may be assumed that it is feasible to use CT-generated preoperative stereotaxic coordinates for reference during an operation, regardless of the patient's position. Four of the 10 patients were examined after lumbar intrathecal administration of metrizamide (200 mg I/ml). This small amount of positive contrast material did not seem to influence the position of the brain.


Neurons undergo apoptosis in animal and cell culture models of diabetes.
Recent clinical trials indicate that the severity of diabetic neuropathy is correlated with the level of patient glycemic control. In the current study, hyperglycemia induces apoptotic changes in dorsal root ganglion neurons and Schwann cells in vivo both in streptozotocin-treated diabetic rats and in rats made acutely hyperglycemic with infused glucose. Typical apoptotic nuclear and cytoplasmic changes are observed. In addition mitochondrial changes recently reported to occur as part of the apoptotic cascade, such as ballooning of mitochondria and disruption of the internal cristae, are seen in diabetic dorsal root ganglion neurons and Schwann cells. Similar changes have been reported in neurons in the presence of oxidative stress. In order to study the neurotoxic effects of high glucose we developed an in vitro model using rat dorsal root ganglion neurons. In dorsal root ganglion cultured in defined medium, addition of moderate glucose levels results in neurite degeneration and apoptosis. These changes are coupled with activation of caspase-3, dependent on the concentration of glucose. The apoptotic changes observed in vitro are similar to those observed in vivo. In contrast, addition of IGF-I, even at physiological concentrations, prevents activation of caspase-3 and neuronal apoptosis in vitro. We suggest that oxidative stress may promote the mitochondrial changes in diabetic animals and lead to activation of programmed cell death caspase pathways. These results imply a new pathogenetic mechanism for diabetic sensory neuropathy.


Borderline Personality Traits Are Not Correlated With Brain Structure in Two Large Samples.
Borderline personality disorder is associated with severe psychiatric presentations and has been linked to variability in brain structure. Dimensional models of borderline personality traits (BPTs) have become influential; however, associations between BPTs and brain structure remain poorly understood. We tested whether BPTs are associated with regional cortical thickness, cortical surface area, and subcortical volumes (n = 152 brain structure metrics) in data from the Duke Neurogenetics Study (n = 1299) and Human Connectome Project (n = 1099). Positive control analyses tested whether BPTs are associated with related behaviors (e.g., suicidal thoughts and behaviors, psychiatric diagnoses) and experiences (e.g., adverse childhood experiences). While BPTs were robustly associated with all positive control measures, they were not significantly associated with any brain structure metrics in the Duke Neurogenetics Study or Human Connectome Project, or in a meta-analysis of both samples. The strongest findings from the meta-analysis showed a positive association between BPTs and volumes of the left ventral diencephalon and thalamus (p values < .005 uncorrected, p values > .1 false discovery rate-corrected). Contrasting high and low BPT decile groups (n = 552) revealed no false discovery rate-significant associations with brain structure. We find replicable evidence that BPTs are not associated with brain structure despite being correlated with independent behavioral measures. Prior reports linking brain morphology to borderline personality disorder may be driven by factors other than traits (e.g., severe presentations, comorbid conditions, severe childhood adversity, or medication) or reflect false positives. The etiology or consequences of BPTs may not be attributable to brain structure measured via magnetic resonance imaging. Future studies of BPTs will require much larger sample sizes to detect these very small effects.


Impact of Antibiotic-Resistant Bacterial and Fungal Infections in Outcome of Acute Pancreatitis.
The knowledge about pathogens and their antibiotic susceptibility patterns is essential to select an appropriate antibiotic. We investigated the microbiological profile in pancreatic and extrapancreatic infections, and antibiotic sensitivity pattern in patients with acute pancreatitis. Of 556 patients with acute pancreatitis, only 189 developed bacterial infection; however, bacteremia was present in 42 patients (7.6%). Culture-proven infected pancreatic necrotic collection was present in 161 patients (29%). Escherichia coli and Klebsiella pneumoniae were the most common organisms. Among the bacterial infection cohort, 164 patients developed multidrug-resistant bacterial infection. Infection with multidrug-resistant bacteria, especially at multiple sites, increased mortality. Nearly 50% of patients (n = 94) acquired extremely drug-resistant bacterial infection at some time and emerged as key reason for prolonged hospital and intensive care unit stay. Colistin resistance and tigecycline resistance were documented in 2.1% and 17.2% of the specimens at admission and in 4.6% and 21% of specimens during the hospital stay. Of 556 patients, 102 patients developed fungal infection and 28 patients had only fungal infection without bacterial infection. Colistin and tigecycline are best reserved as last-resort antibiotics. Fungal infection was found to be associated with increased mortality, median hospital stay, and intensive care unit stay.


The influence of vector-borne disease on human history: socio-ecological mechanisms.
Vector-borne diseases (VBDs) are embedded within complex socio-ecological systems. While research has traditionally focused on the direct effects of VBDs on human morbidity and mortality, it is increasingly clear that their impacts are much more pervasive. VBDs are dynamically linked to feedbacks between environmental conditions, vector ecology, disease burden, and societal responses that drive transmission. As a result, VBDs have had profound influence on human history. Mechanisms include: (1) killing or debilitating large numbers of people, with demographic and population-level impacts; (2) differentially affecting populations based on prior history of disease exposure, immunity, and resistance; (3) being weaponised to promote or justify hierarchies of power, colonialism, racism, classism and sexism; (4) catalysing changes in ideas, institutions, infrastructure, technologies and social practices in efforts to control disease outbreaks; and (5) changing human relationships with the land and environment. We use historical and archaeological evidence interpreted through an ecological lens to illustrate how VBDs have shaped society and culture, focusing on case studies from four pertinent VBDs: plague, malaria, yellow fever and trypanosomiasis. By comparing across diseases, time periods and geographies, we highlight the enormous scope and variety of mechanisms by which VBDs have influenced human history.


Intraoperative Near-infrared Fluorescence Imaging with Novel Indocyanine Green-Loaded Nanocarrier for Spinal Metastasis: A Preliminary Animal Study.
Marginal resection during resection of a spinal metastasis is frequently difficult because of the presence of important tissues such as the aorta, vena cava, and dura mater, including the spinal cord adjacent to the vertebral body. Thus, there is an urgent need for novel intraoperative imaging modalities with the ability to clearly identify bone metastasis. We have proposed a novel nanocarrier loaded with indocyanine green (ICG) (ICG-lactosome) with tumor selectivity attributable to its enhanced permeation and retention (EPR) effect. We studied its feasibility in intraoperative near-infrared (NIR) fluorescence diagnosis with ICG-lactosome for imaging spinal metastasis. A rat model of subcutaneous mammary tumor and a rat model of spinal metastasis of breast cancer were used. Fluorescence emitted by the subcutaneous tumors and the spinal metastasis were clearly detected for at least 24 h. Moreover, imaging of the dissected spine revealed clear fluorescence emitted by the metastatic lesion in the L6 vertebra while the normal bone lacked fluorescence. This study was the first report on NIR fluorescence imaging of spinal metastasis in vivo. NIR fluorescence imaging with ICG-lactosome could be an effective intraoperative imaging modality for detecting spinal metastasis.


Bondable reinforcement ribbon: clinical applications.
Bondable reinforcement ribbon can be used in dentistry to splint periodontally involved teeth, to provide postorthodontic splinting, to reinforce provisional prostheses, and to fabricate direct adhesive prostheses. Four cases illustrate esthetically and functionally successful use of reinforced ribbon.


Novel Tools in Determining the Physiological Demands and Nutritional Practices of Ontario FireRangers during Fire Deployments.
The seasonal profession of wildland fire fighting in Canada requires individuals to work in harsh environmental conditions that are physically demanding. The purpose of this study was to use novel technologies to evaluate the physiological demands and nutritional practices of Canadian FireRangers during fire deployments. Participants (n = 21) from a northern Ontario Fire Base volunteered for this study and data collection occurred during the 2014 fire season and included Initial Attack (IA), Project Fire (P), and Fire Base (B) deployments. Deployment-specific energy demands and physiological responses were measured using heart-rate variability (HRV) monitoring devices (Zephyr BioHarness3 units). Food consumption behaviour and nutrient quantity and quality were captured using audio-video food logs on iPod Touches and analyzed by NutriBase Pro 11 software. Insufficient kilocalories were consumed relative to expenditure for all deployment types. Average daily kilocalories consumed: IA: 3758 (80% consumption rate); P: 2945±888.8; B: 2433±570.8. Average daily kilocalorie expenditure: IA: 4538±106.3; P: 4012±1164.8; B: 2842±649.9. The Average Macronutrient Distribution Range (AMDR) for protein was acceptable: 22-25% (across deployment types). Whereas the AMDR for fat and carbohydrates were high: 40-50%; and low: 27-37% respectively, across deployment types. This study is the first to use the described methodology to simultaneously evaluate energy expenditures and nutritional practices in an occupational setting. The results support the use of HRV monitoring and video-food capture, in occupational field settings, to assess job demands. FireRangers expended the most energy during IA, and the least during B deployments. These results indicate the need to develop strategies centered on maintaining physical fitness and improving food practices.


Binding of urokinase to plasminogen activator inhibitor type-1 mediates cell adhesion and spreading.
Urokinase plasminogen activator and its receptor are both found at the surface of the cell membrane in many cell types. The plasminogen activator inhibitor type-1 (PAI-1) is often associated with the extracellular matrix. The spatial localization of these three molecules could account for their involvement in cell adhesion and/or migration. We have shown previously that the urokinase receptor mediates mechanical force transmission across the cell surface to the cytoskeleton. Here we investigated whether immobilized plasminogen activator inhibitor type 1 (PAI-1) could regulate cell spreading and cytoskeleton reorganization. Serum deprived human myogenic cells were plated in serum free medium onto bacteriologic dishes precoated with different extracellular matrix ligands (fibronectin, vitronectin, or type 1 collagen) or PAI-1 at increasing concentrations. The number of adherent cells and their projected area were quantitated after 3 hours of plating. PAI-1 promoted cell adhesion and spreading in a dose dependent manner. Addition of antibodies to PAI-1 inhibited the adhesion on PAI-1 coated dishes in a dose dependent way. The PAI-1 mediated cell adhesion required the presence of urokinase at the cell surface. Removal of the glycosylphosphatidylinositol (GPI)-linked proteins abolished cell adhesion on PAI-1 dish, suggesting its dependence on the presence of the urokinase receptor, a GPI-linked receptor. Furthermore, addition of antibodies against alpha v beta3 integrin completely inhibited cell adhesion on PAI-1, suggesting that alpha v beta3 might be the transmembrane molecule that physically connects the complex of PAI-1, urokinase, and urokinase receptor to the cytoskeleton. Visualization of spread cells stained for filamentous actin with confocal microscopy showed a dose-dependent increase of filopodia on PAI-1 coated dishes and cytoskeletal reorganization, suggesting a migratory profile. These data indicate that PAI-1 plays a direct role in dynamic cell adhesion particularly at the leading edge, where increased levels of urokinase plasminogen activator (uPA) and its receptor (uPAR) are localized in migrating cells. Immobilized PAI-1 could therefore serve to bridge the cell surface with the extracellular matrix via the formation of a multimolecular complex that includes alpha v beta3 integrins in myogenic cells.


Neutrophil elastase-processing defect in cyclic hematopoietic dogs.
Canine cyclic hematopoiesis (CH), a model of human cyclic neutropenia and severe congenital neutropenia, is characterized by a periodic reduced neutrophil count and decreased neutrophil elastase (NE) enzymatic activity. Canine CH is caused by a mutation of AP3B1 encoding the beta3A subunit of adaptor protein complex-3 (AP-3). It has been proposed that trafficking of elastase is affected by AP-3. The aim of this study was to study intracellular sorting/trafficking of NE in CH dogs using antibodies specific to canine NE. Polyclonal and monoclonal antibodies were generated to immunogenic epitopes in the middle (aa85-98) and C-terminal (aa269-282) regions of NE. The antibodies to canine NE were characterized by Western immunoblotting and immunocytochemistry. Antibody ELA85 (antibody to canine NE aa 85-98) specifically recognized mature 28-kD NE. Immunocytochemical analysis using ELA85 and an antibody to myeloperoxidase demonstrated colocalizaton of NE and myeloperoxidase in primary granules of normal dogs. Antibody ELA269 (antibody to canine NE aa 269-282) reacted exclusively with the 33-kD NE presumptive precursor form. Immunocytochemical analysis demonstrated that the NE precursor was not colocalized with myeloperoxidase in the primary granules of normal or CH dogs. Western immunoblotting using these antibodies demonstrated that CH dogs contained reduced mature NE, but accumulated a large amount of the NE precursor protein that was not enzymatically active. Antibodies ELA85 and ELA269 were found to be useful reagents for studying the biosynthesis, processing, and trafficking of NE during normal myelopoiesis. Neutrophils from CH dogs accumulated large amounts of higher molecular weight elastase precursors compared to normal dogs.


Invasive adenoma and pituitary carcinoma: a SEER database analysis.
Invasive pituitary adenomas and pituitary carcinomas are clinically indistinguishable until identification of metastases. Optimal management and survival outcomes for both are not clearly defined. The purpose of this study is to use the Surveillance, Epidemiology, and End Results (SEER) database to report patterns of care and compare survival outcomes in a large series of patients with invasive adenomas or pituitary carcinomas. One hundred seventeen patients diagnosed between 1973 and 2008 with pituitary adenomas/adenocarcinomas were included. Eighty-three invasive adenomas and seven pituitary carcinomas were analyzed for survival outcomes. Analyzed prognostic factors included age, sex, race, histology, tumor extent, and treatment. A significant decrease in survival was observed among carcinomas compared to invasive adenomas at 1, 2, and 5 years (p = 0.047, 0.001, and 0.009). Only non-white race, male gender, and age ≥65 were significant negative prognostic factors for invasive adenomas (p = 0.013, 0.033, and <0.001, respectively). There was no survival advantage to radiation therapy in treating adenomas at 5, 10, 20, or 30 years (p = 0.778, 0.960, 0.236, and 0.971). In conclusion, pituitary carcinoma patients exhibit worse overall survival than invasive adenoma patients. This highlights the need for improved diagnostic methods for the sellar phase to allow for potentially more aggressive treatment approaches.


Reducing uncertainty in the american community survey through data-driven regionalization.
The American Community Survey (ACS) is the largest survey of US households and is the principal source for neighborhood scale information about the US population and economy. The ACS is used to allocate billions in federal spending and is a critical input to social scientific research in the US. However, estimates from the ACS can be highly unreliable. For example, in over 72% of census tracts, the estimated number of children under 5 in poverty has a margin of error greater than the estimate. Uncertainty of this magnitude complicates the use of social data in policy making, research, and governance. This article presents a heuristic spatial optimization algorithm that is capable of reducing the margins of error in survey data via the creation of new composite geographies, a process called regionalization. Regionalization is a complex combinatorial problem. Here rather than focusing on the technical aspects of regionalization we demonstrate how to use a purpose built open source regionalization algorithm to process survey data in order to reduce the margins of error to a user-specified threshold.


Collision Cross Section (CCS) Database: An Additional Measure to Characterize Steroids.
Ion mobility spectrometry enhances the performance characteristics of liquid chromatography-mass spectrometry workflows intended to steroid profiling by providing a new separation dimension and a novel characterization parameter, the so-called collision cross section (CCS). This work proposes the first CCS database for 300 steroids (i.e., endogenous, including phase I and phase II metabolites, and exogenous synthetic compounds), which involves 1080 ions and covers the CCS of 127 androgens, 84 estrogens, 50 corticosteroids, and 39 progestagens. This large database provides information related to all the ionized species identified for each steroid in positive electrospray ionization mode as well as for estrogens in negative ionization mode. CCS values have been measured using nitrogen as drift gas in the ion mobility cell. Generally, direct correlation exists between mass-to-charge ratio ( m/ z) and CCS because both are related parameters. However, several steroids mainly steroid glucuronides and steroid esters have been characterized as more compact or elongated molecules than expected. In such cases, CCS results in additional relevant information to retention time and mass spectral data for the identification of steroids. Moreover, several isomeric steroid pairs (e.g., 5β-androstane-3,17-dione and 5α-androstane-3,17-dione) have been separated based on their CCS differences. These results indicate that adding the CCS to databases in analytical workflows increases selectivity, thus improving the confidence in steroids analysis. Consequences in terms of identification and quantification are discussed. Quality criteria and a construction of an interlaboratory reproducibility approach are also reported for the obtained CCS values. The CCS database described here is made publicly available.


Methyl palmitate reversed estradiol benzoate-induced endometrial hyperplasia in female rats.
Early detection and treatment of endometrial hyperplasia (EH) is mandatory for endometrial cancer prevention. Several bioactive agents of plant origin have been shown to elicit their chemotherapeutic effect against tumors and cancer via induction of mitochondrial permeability transition(mPT) pore opening. This research was therefore aimed at evaluating the potential chemopreventive effect of methyl palmitate (MP), on estradiol benzoate(EB)-induced EH, looking at the mitochondrial-mediated pathway and other possible mechanisms of action. Mitochondria were isolated using differential centrifugation. The mPT pore, mitochondrial ATPase (mATPase) activity, lipid peroxidation and cytochrome c release were determined by standard methods using spectrophotometer. Uterine interleukin 1b, MDA levels and SOD, GSH activities, were determined using commercially available kits. The uterine histological and immunohistochemical assessment of estrogen receptor (ERα), IL-1b and caspas-3 were carried out. The fibroblast cell count density was determined using histomorphometry. At all the concentrations of MP used, there was no significant induction of mPT pore opening, neither any enhancement of mATPase activity nor release of cytochrome c when compared to the control. Similar pattern of results were recorded for the in vivo study. However, there was marked increase in the uterine MDA and interleukin 1b levels, with concurrent decrease in SOD and GSH activities, in the EB-treated group, which was significantly reversed by MP co-administration. Endometrial Hyperplasia observed in the EB-treated group was ameliorated by MP co-administration. The immunoexpression of ERα and IL-1b in the EB-treated group was reversed by MP co-administration. This study suggests anti-inflammatory, antioxidant and anti-proliferative potential of MP against EB-induced EH.


Tokaracetin, a new platelet antagonist that binds to platelet glycoprotein ib and inhibits von Willebrand factor-dependent shear-induced platelet aggregation.
A new platelet antagonist, tokaracetin, was isolated from the venom of Trimeresurus tokarensis by ion-exchange chromatography, heparin-Sepharose chromatography and hydrophobic HPLC. The purified protein showed an apparent molecular mass on SDS/PAGE of 28.9 kDa under non-reducing conditions. On reduction, 16.1 and 15.4 kDa subunits were observed, suggesting that the molecule is a heterodimer. Tokaracetin inhibited the binding of 125I-labelled bovine von Willebrand factor (vWF) and 125I-labelled human vWF in the presence of botrocetin to fixed human platelets. It did not block ADP-, collagen- or thrombin receptor agonist peptide-induced platelet aggregation in human platelet-rich plasma (PRP), or induce platelet agglutination in PRP. On reduction, tokaracetin lost its inhibitory activity on the agglutination of fixed human platelets by bovine vWF. 125I-Tokaracetin specifically bound to washed human platelets with high affinity (Kd 3.9 +/- 1.4 nM) at 47,440 +/- 2780 binding sites per platelet. Binding of tokaracetin to fixed human platelets was reversible, and was inhibited by monoclonal antibody GUR83-35, which is directed against the N-terminal vWF-binding domain of human glycoprotein Ib (GPIb). Tokaracetin completely inhibited vWF-dependent shear-induced platelet aggregation in PRP at 3 micrograms/ml. The N-terminal amino acid sequences of tokaracetin subunits showed a high degree of identity with those of alboaggregin-B. These results suggest that this new platelet antagonist may be a useful tool in the development of specific inhibitors of the vWF-GPIb interaction.