Frequency comparison of two high-accuracy Al+ optical clocks.
We have constructed an optical clock with a fractional frequency inaccuracy of 8.6x10{-18}, based on quantum logic spectroscopy of an Al+ ion. A simultaneously trapped Mg+ ion serves to sympathetically laser cool the Al+ ion and detect its quantum state. The frequency of the {1}S{0}<-->{3}P{0} clock transition is compared to that of a previously constructed Al+ optical clock with a statistical measurement uncertainty of 7.0x10{-18}. The two clocks exhibit a relative stability of 2.8x10{-15}tau{-1/2}, and a fractional frequency difference of -1.8x10{-17}, consistent with the accuracy limit of the older clock.


Towards a history of European physical sensibility: pain in the later Middle Ages.
The study of pain in a historical context requires a consideration of the cultural context in which pain is sensed and expressed. This paper examines attitudes toward physical pain in the later Middle Ages in Europe from several standpoints: theology, law, and medicine. During the later Middle Ages attitudes toward pain shifted from rejection and a demand for impassivity as a mark of status to a conscious attempt to sense, express, and inflict as much pain as possible. Pain became a positive force, a useful tool for reaching a variety of truths. While this attitude stemmed from the religious wish to identify with Christ's passion, it permeated and affected all spheres of cultural expression and investigation. Late medieval medicine accepted pain, trying to relieve it only when it became dangerous to the patient. Given the existence of analgesic medicines at the time, this attitude is comprehensible only within the cultural context of that period.


A Preclinical Rodent Model for Repetitive Subconcussive Head Impact Exposure in Contact Sport Athletes.
Repetitive subconcussive head impact exposure has been associated with clinical and MRI changes in some non-concussed contact sport athletes over the course of a season. However, analysis of human tolerance for repeated head impacts is complicated by concussion and head impact exposure history, genetics, and other personal factors. Therefore, the objective of the current study was to develop a rodent model for repetitive subconcussive head impact exposure that can be used to understand injury mechanisms and tolerance in the human. This study incorporated the Medical College of Wisconsin Rotational Injury Model to expose rats to multiple low-level head accelerations per day over a 4-week period. The peak magnitude of head accelerations were scaled from our prior human studies of contact sport athletes and the number of exposures per day were based on the median (moderate exposure) and 95th percentile (high exposure) number of exposures per day across the human sample. Following the exposure protocol, rats were assessed for cognitive deficits, emotional changes, blood serum levels of axonal injury biomarkers, and histopathological evidence of injury. High exposure rats demonstrated cognitive deficits and evidence of anxiety-like behaviors relative to shams. Moderate exposure rats did not demonstrate either of those behaviors. Similarly, high exposure rats had histopathological evidence of gliosis [i.e., elevated Iba1 intensity and glial fibrillary acidic protein (GFAP) volume relative to shams] in the basolateral amygdala and other areas. Blood serum levels of neurofilament light (NFL) demonstrated a dose response relationship with increasing numbers of low-level head acceleration exposures with a higher week-to-week rate of NFL increase for the high exposure group compared to the moderate exposure group. These findings demonstrate a cumulative effect of repeated low-level head accelerations and provide a model that can be used in future studies to better understand mechanisms and tolerance for brain injury resulting from repeated low-level head accelerations, with scalable biomechanics between the rat and human.


Influence of matching volume on reproducibility of maximal expiratory flow-volume curves.
We examined the influence of "matching volume" on intrasubject variability of the descending limb of maximal expiratory flow-volume (MEFV) curves on air and helium-oxygen (He) in 18 healthy subjects and 28 patients with airflow limitation. Duplicate forced expirations were analysed according to four methods of alignment. With the first method, flows corresponding to identical percentiles of separate FVC (SEPVC) were compared. With the remaining three, we aligned curves at TLC, mid-vital capacity (VC50) and RV, respectively, for comparison of: a) flow at identical percentiles of the averaged FVC and b) expired volume at identical percentiles of the averaged peak flow. In healthy subjects, variability of flow at 50% and 75% of expired FVC (FEF50 and FEF75) did not change significantly with method, except that FEF75 on air varied more with method SEPVC than with VC50. In airflow limitation, FEF75 was significantly less reproducible when curves were matched at RV than at TLC, both on air and He. Over the latter part of expiration, an arbitrary index of variability of flow-defined volume also indicated that method RV gave the poorest precision in patients. We conclude that selection of matching volume does not influence the variability of MEFV-curves in health. In airflow limitation, however, TLC appears to be the most reliable volume for alignment.


CircRNA_001010 adsorbs miR-5112 in a sponge form to promote proliferation and metastasis of non-small cell lung cancer (NSCLC).
It has been demonstrated that circular RNA (circRNA) plays an important regulatory role in a series of diseases. The purpose of this study is to investigate the expression of circRNA_001010 and its facilitating effects on proliferation and invasion of non-small cell lung cancer (NSCLC) by regulating oncogene CDK4 through sponging with miR-5112. qRT-PCR was performed to detect the expressions of circRNA_001010 and CDK4 in human NSCLC tissues and cells. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the A549 cells proliferation and transwell assay was performed to evaluate the A549 cells migration. Correlation analysis between circRNA_001010 and miR-5112 was detected by statistical analysis. Bioinformatics prediction was made to detect the binding site of GTL and miR-5112 and Luciferase activity was conducted to investigate the interaction between circRNA_001010 and miR-5112. Furthermore, we cloned the mice CDK4 3'-UTR into the Luciferase reporter vector and constructed miR-5112 binding mutants to validate the inhibited modulation of miR-5112 to the CDK4 expression. Results showed that the expressions of circRNA_001010 and CDK4 were upregulated in human NSCLC tissues and cells. qRT-PCR and CCK-8 assay showed that circRNA_001010 expression is associated with the proliferation of NSCLC cells, and that upregulated circRNA_001010 contributed to cell proliferation of A549. Transwell assay showed that circRNA_001010 was associated with the migration ability of tumor cells, and that increased expression of circRNA_001010 promoted the migration and invasion of NSCLC cells. The bioinformatics prediction and Luciferase assay demonstrated that by sponging with miR-5112, circRNA_001010 can serve as a ceRNA for miR-5112 to further regulate the expression of CDK4. For the first time, we found that circRNA_001010 was upregulated in human NSCLC patients, which could accelerate tumor proliferation, migration and invasion as a molecular sponge by modulating the inhibitory effect of miR-5112 on oncogene CDK4.


Combined Astigmatic Arcuate Keratotomy with Descemet Automated Endothelial Keratoplasty.
We report the results of simultaneous astigmatic arcuate keratotomy (AK) and Descemet automated endothelial keratoplasty (DSAEK). A 55-year-old patient with a history of high myopia was referred for the management of bullous keratopathy secondary to an anterior chamber phakic intraocular lens (pIOL). IOL explantation through a 5.5-mm corneal incision, cataract extraction, and posterior chamber IOL implantation, combined with DSAEK, were performed. Postoperatively, increased astigmatism up to 2.0 diopters (Dpt) was observed, attributed to the large corneal incision, and remained stable, despite suture removal at 3 months. One year postoperatively, the graft showed signs of progressive endothelial dysfunction. A combined procedure of astigmatic AK and DSAEK was thus performed. After 6 months, topographic astigmatism was significantly reduced to 0.5 Dpt and best-corrected visual acuity increased. In conclusion, simultaneous astigmatic AK and DSAEK could be an effective combination for treating patients with well-documented pre-existing astigmatism and endothelial decompensation.


Online Gambling Advertising Regulations in Spain. A Study on the Protection of Minors.
This article examines the online gambling advertising regulations in Spain currently in effect to assess the actual protection of underage youth. In recent years, online gambling among youth has increased. Through advertising, online gambling companies incite and encourage an involvement that can be harmful for vulnerable audiences. Some studies have demonstrated that advertising influences youths' assessment of gambling by increasing its appeal. We demonstrate that the shortcomings of the legal framework in force results in effective vulnerability of minors. We claim that society should seek to implement a regulatory framework to protect children from the risk of developing an addiction.


Congenital mirror movement associated with migraine: A case report.
Mirror movements occur in early childhood due to the maturation of the corpus callosum of noncrossing motor pathways. Such movements are considered normal until the age of 10 and are rarely reported in children older than 10 years. Mirror movements are involuntary movements that occur in the homologous contralateral extremity on voluntary activation. Permanent mirror movements can occur with anomalies; however, also are reported familial and sporadic cases. Migraine is the most common primary headache in childhood. Its prevalence ranges from 1% to 3% between the ages of 3 and 7, and from 8% to 23% in the adolescence. The prevalence of migraine in adolescent girls is higher. For the migraine diagnosis, the imaging studies are unnecessary, and a detailed history and physical examination are sufficient. In this study, we present a case of a 17-year-old girl with mirror movements accompanied by migraine.


High School Students With Reading Comprehension Difficulties: Results of a Randomized Control Trial of a Two-Year Reading Intervention.
A 2-year, randomized control trial with 9th to 10th grade students with significant reading problems was provided for 50 minutes a day in small groups. Comparison students were provided an elective class and treatment students the reading intervention. Students were identified as demonstrating reading difficulties through failure on their state accountability test and were randomly assigned to one of three treatment conditions and a business as usual (BAU) condition: reading without dropout prevention, reading with dropout prevention, dropout prevention without reading, or a BAU condition. Findings from the 2-year reading intervention (reading with and without dropout prevention combined and BAU) are reported in this article. Students in reading treatment compared to students in BAU demonstrated significant gains on reading comprehension (effect size = .43), and improved reading was associated with better grades in social studies. Findings from this study provide a rationale for further implementation and investigation of intensive intervention for high school students with reading difficulties.


Massive intoxication involving unusual high concentration of amitriptyline.
Amitriptyline is a tricyclic antidepressant widely used in the treatment of depression. Antidepressant drugs are among the most commonly encountered causes of self-poisoning, as illustrated by several published cases in the literature. This investigation reports a case of massive amitriptyline intoxication, involving a 44-year old female found dead in bed. The presence of this tricyclic antidepressant was revealed by a routine screening procedure. The concentration was calculated by gas chromatography/ electron ionization-mass spectrometry in the selected ion monitoring mode after solid-phase extraction using proadifen as internal standard and was in the post-mortem whole blood sample 85.9 mug/mL. This value was much higher than the reported toxic values ever found in the literature, and may therefore have caused the victim's death. Nortriptyline was also detected in the toxic concentration range, as well as therapeutic levels of diazepam and nor-diazepam. Taking into account both the available circumstantial information and toxicological results, it is very likely that death was caused by self-poisoning. Human & Experimental Toxicology (2007) 26, 667-670.


A comparison of cognitive-behavioral therapy, sertraline, and their combination for adolescent depression.
To evaluate cognitive-behavioral therapy, antidepressant medication alone, and combined CBT and antidepressant medication in the treatment of depressive disorders in adolescents. Seventy-three adolescents (ages 12-18 years) with a primary diagnosis of DSM-IV major depressive disorder, dysthymic disorder, or depressive disorder not otherwise specified were randomly allocated to one of three treatments. Treatment outcome measures were administered before and after acute treatment, and at a 6-month follow-up. Depression diagnosis was the primary outcome measure; secondary measures were self- and other report and clinician rating of global functioning. The trial was conducted at three community-based clinics between July 2000 and December 2002. Data analyses used an intent-to-treat strategy. Following acute treatment, all treatment groups demonstrated statistically significant improvement on outcome measures (depressive diagnosis, Reynolds Adolescent Depression Scale, Revised Children's Manifest Anxiety Scale, Suicidal Ideation Questionnaire), and improvement was maintained at follow-up. Combined cognitive-behavioral therapy and antidepressant medication was not found to be superior to either treatment alone. Compared with antidepressant medication alone, participants receiving cognitive-behavioral therapy alone demonstrated a superior acute treatment response (odds ratio = 6.86; 95% confidence interval 1.12-41.82). Although cognitive-behavioral therapy was found to be superior to antidepressant medication alone for the acute treatment of mild to moderate depression among youth, this may have stemmed from the relatively low dose of sertraline used. All treatments led to a reduction in depression, but the advantages of a combined approach were not evident.


From Froot Loops to Fitness: My Journey as an Educator and Person With Diabetes.
EDITOR'S NOTE: This article is adapted from the address Dr. Colberg delivered as the recipient of the American Diabetes Association's Outstanding Educator in Diabetes Award for 2016. She delivered the address in June 2016 at the association's 76th Annual Meeting and Scientific Sessions in New Orleans, La. A webcast of this speech is available for viewing at the ADA website (http://professional.diabetes.org/search/site?f%5B0%5D=im_field_dbp_ct%3A7&f%5B1%5D=sm_field_wcast_mname%3Anode%3A120&retain-filters=1).


Life dissatisfaction is associated with depression and poorer surgical outcomes among lumbar spinal stenosis patients: a 10-year follow-up study.
Life satisfaction is associated with overall somatic health and the short-term surgical outcome in lumbar spinal stenosis (LSS) patients. In this study, the long-term relationship between life satisfaction and the surgical outcome in LSS patients was investigated in a 10-year follow-up. This prospective clinical study included 102 LSS patients who underwent decompressive surgery. They completed a set of questionnaires first preoperatively and then 6 times postoperatively (at 3 and 6 months, and at 1, 2, 5 and 10 years). The final study population at the 10-year follow-up comprised 72 patients. A four-item life satisfaction scale was used to measure global life satisfaction. The sum of all seven life satisfaction scores provided a measure of the life dissatisfaction burden over the entire 10-year follow-up. Depression was measured using the Beck Depression Inventory. The surgical outcome was evaluated using the Oswestry Disability Index, pain evaluation (visual analogue scale), self-reported walking capacity and overall satisfaction with the surgery. Both preoperative life dissatisfaction and the long-term life dissatisfaction burden were associated with poorer 10-year surgical outcomes (i.e. Oswestry Disability Index and visual analogue scale) in logistic regression analyses. Life dissatisfaction was also associated with symptoms of depression. Monitoring subjective well-being, especially life satisfaction and mood, in LSS patients before and after surgery may help in detecting those at risk of a poorer long-term surgical outcome.


Forty-nine years in Biomaterials Science: an interview with Buddy Ratner.
Buddy Ratner talks to Francesca Lake, Managing Editor. After receiving his PhD in polymer chemistry from the Polytechnic Institute of Brooklyn (USA) in 1972, Ratner moved to the University of Washington (USA), where he has since become joint professor of bioengineering and chemical engineering and Michael L & Myrna Darland Endowed Chair in Technology Commercialization. Since 1996, he has led the UWEB Research Center for Biomaterials at the University of Washington, originally funded by the National Science Foundation. A pioneer of the biomaterials field, Ratner's research interests include biomaterials, tissue engineering, polymers, biocompatibility and surface analysis of organic materials. A leader in the field, he has received numerous awards, has launched several companies and holds over 20 patents.


Surgical Options for Uhl's Anomaly.
Uhl's anomaly is an extremely rare congenital heart defect characterized by a near total absence of the myocardium of the parietal wall of the right ventricle. Few reports of surgical management exist in literature. We present three patients with this anomaly who were managed with different surgical strategies. Patient 1: This 43-month-old girl had maternal rubella syndrome with speech and hearing deficits and gross right heart failure. Diagnosis was made on echocardiography and magnetic resonance imaging. She underwent partial excision and plication of the right ventricular parietal wall and total cavopulmonary connection. Patient 2: This 19-month-old boy presented with progressive cyanosis and features of right heart failure. Diagnosis was confirmed on echocardiography. He underwent right ventricular exclusion by tricuspid valve closure and free wall plication followed by a bidirectional Glenn procedure. Patient 3: This 21-year-old male presented with right heart failure and cyanosis. Diagnosis was established with transesophageal echocardiography and magnetic resonance imaging. As the hemodynamics were not suitable for a Fontan conversion, a one and a half ventricle repair was done along with plication of the right ventricular free wall and tricuspid valve annuloplasty. All three patients were extubated within 24 hours. Patients 2 and 3 were discharged relatively uneventfully, whereas patient 1 had a more prolonged stay due to transient hepatic failure. All were symptomatically and clinically improved on short-term follow-up. Uhl's anomaly is an extremely rare condition with varied clinical presentation. Surgical exclusion of the right ventricle yields gratifying results; however, surgical technique has to be adapted to the individual patient.


Causality, mathematical models and statistical association: dismantling evidence-based medicine.
From humble beginnings, largely at the medical school at McMaster University, Canada, the evidence-based medicine (EBM) movement has enjoyed a spectacular rise in international acceptance over the last 25 years. Randomized controlled trials (RCTs) and systematic reviews based on them have pride of place (the gold standard) in EBM's hierarchy of evidence; models and theories are relegated to the bottom of the hierarchy. In the last decade, RCTs have been extensively criticized. I briefly rehearse those criticisms because they are an important backdrop to the criticism of EBM developed in this paper. In essence, the argument developed here is that RCTs use mathematics solely as a tool of analysis rather than as the language of the science and that this fundamentally affects the validity of causal claims. As EBM gives pride of place to RCTs and devalues theoretical models - a devaluation that would be incomprehensible to a physicist or biologist - the validity of EBM's causal claims and knowledge claims are weak and far from a 'gold standard'.


Counseling to prevent skin cancer: recommendations and rationale of the U.S. Preventive Services Task Force.
This statement summarizes the current U.S. Preventive Services Task Force (USPSTF) recommendation on counseling to prevent skin cancer and the supporting scientific evidence, and updates the 1996 recommendation contained in the Guide to Clinical Preventive Services, Second Edition (U.S. Preventive Services Task Force. Screening for skin cancer. In: Guide to clinical preventive services, 2nd ed. Washington DC: US Department of Health and Human Services, Office of Disease Prevention and Health Promotion, 1996:141-52). The USPSTF finds insufficient evidence to recommend for or against routine counseling by primary care clinicians to prevent skin cancer. Although counseling parents may increase children's use of sunscreen, the USPSTF found little evidence to determine the effects of counseling on the sun protection behaviors of adults. These behaviors include wearing protective clothing, reducing excessive sun exposure, avoiding sun lamps and tanning beds, or practicing skin self-examination. The USPSTF, an independent panel of private sector experts in primary care and prevention, systematically reviews the evidence of effectiveness of a wide range of clinical preventive services, including screening tests, counseling, and chemoprevention. Members of the USPSTF represent the fields of family medicine, gerontology, obstetrics/gynecology, pediatrics, nursing, and prevention research.


Predictors of household food insecurity and relationship with obesity in First Nations communities in British Columbia, Manitoba, Alberta and Ontario.
To further understandings of household food insecurity in First Nations communities in Canada and its relationship with obesity. Analysis of a cross-sectional dataset from the First Nations Food, Nutrition and Environment Study representative of First Nations communities south of the 60th parallel. Multivariate logistic regression was used to assess associations between food insecurity and sociodemographic factors, as well as the odds of obesity among food-insecure households adjusting for sociodemographic characteristics. Western and Central Canada. First Nations peoples aged ≥19 years. Forty-six percent of First Nations households experienced food insecurity. Food insecurity was highest for respondents who received social assistance; had ≤10 years of education; were female; had children in the household; were 19-30 years old; resided in Alberta; and had no year-round road access into the community. Rates of obesity were highest for respondents residing in marginally food-insecure households (female 56·6 %; male 54·6 %). In gender-specific analyses, the odds of obesity were highest among marginally food-insecure households in comparison with food-secure households, for both female (OR 1·57) and male (OR 1·57) respondents, adjusting for sociodemographic variables. For males only, those in severely food-insecure (compared with food-secure) households had lower odds of obesity after adjusting for confounding (OR 0·56). The interrelated challenges of food insecurity and obesity in First Nations communities emphasise the need for Indigenous-led, culturally appropriate and food sovereign approaches to food security and nutrition in support of holistic wellness and prevention of chronic disease.


Effects of acute high-Intensity resistance exercise on cognitive function and oxygenation in prefrontal cortex.
Moderate-intensity exercise is known to be the best effective intensity to enhance cognitive function, including memory and learning. However, the effects of high-intensity exercise in comparison with moderate- intensity exercise on cognitive function remain controversial. The aim of this study was to investigate the effect of high-intensity resistance exercise on cognitive function. Thirty-six healthy female college students volunteered to participate in this study. The participants were divided into four groups: (i) control group (CON); (ii) high-intensity resistance exercise group (HIR); (iii) high-intensity aerobic exercise group (HIA); and (iv) combined moderate-intensity exercise group (MIC). Immediately prior to and after exercise, the solved number (SN) and reaction times (RT) in the Stroop test (neutral task, NT and incongruent task, IT), as well as the tissue oxygen index (TOI) in the left and right prefrontal cortex (PFC) were measured in all groups. In the NT, both HIR and MIC groups showed significant improvements in SN and RT compared with the CON group. Meanwhile, performance in the HIA group was significantly attenuated compared with that in the MIC group. In the IT, only the MIC group showed a significant increase in SN and RT compared with the CON group. Furthermore, the TOI in the PFC (left PFC in the NT, and bilaterally in the IT) was significantly lower in the HIR group compared with that in the CON group. The results of this study show worse cognitive performance and decreased PFC oxygenation in high-intensity exercise compared with moderate-intensity exercise and controls. These results suggest that high-intensity exercise may not improve cognition as effectively as moderate-intensity exercise.


Higher Gene Expression of Healing Factors in Anterior Cruciate Ligament Remnant in Acute Anterior Cruciate Ligament Tear.
Anterior cruciate ligament (ACL) reconstruction with remnant preservation has been described and related to potential advantages. Literature is lacking regarding gene expression of potential factors related to ligament healing in the ACL remnant and its relation to time from injury. The mRNA expression of ligament healing factors in the ACL remnant would be higher in acute tears (<3 months from injury) than in intermediate (3-12 months) and chronic (>12 months) injuries. Controlled laboratory study. Gene expression of 21 genes related to ligament healing factors was analyzed in 46 ACL remnants biopsied during surgical reconstruction with quantitative real-time polymerase chain reaction technique. Specimens were divided into 3 groups according to time from injury: acute (<3 months from injury; n = 19), intermediate (3-12 months; n = 12), and chronic (>12 months; n = 15). Histological and immunohistochemical evaluation was performed by analysis of hematoxylin and eosin, CD-34, and S-100 staining. Expression of COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL12A1, LOX, PLOD1, and TNC genes in ACL remnant was greater in acute compared with chronic injuries. COL1A1, COL5A1, COL12A1, and TNC genes were also expressed more in the acute group compared with the intermediate group. Furthermore, expression of the genes COL1A1 and COL5A2 was significantly higher in female than in male patients. No difference in the number of blood vessels and mechanoreceptors among groups was observed in the microscopic evaluation. The present study demonstrates that expression of COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, COL12A1, LOX, PLOD1, and TNC genes in ACL remnant is greater in acute (<3 months from injury) compared with chronic (>12 months) injuries. Furthermore, COL1A1, COL5A1, COL12A1, and TNC genes were expressed more in the acute group compared with the intermediate group (3-12 months from injury). ACL reconstructions with remnant preservation should be performed in patients with acute injuries, as in these cases the ACL remnant may present the greatest healing potential.


Genetic variants in nitric oxide synthase genes and the risk of male infertility in a Chinese population: a case-control study.
In recent years, oxidative stress has been studied extensively as a main contributing factor to male infertility. Nitric Oxide, a highly reactive free radical gas, is potentially detrimental to sperm function and sperm DNA integrity at high levels. Thus, the aim of this study was to investigate the associations between five polymorphisms in nitric oxide synthase genes (NOSs) and the risk of male infertility and sperm DNA damage as well. Genotypes were determined by the OpenArray platform. Sperm DNA fragmentation was detected using the Tdt-mediated dUTP nick-end labeling assay, and the level of 8-hydroxydeoxyguanosine (8-OHdG) in sperm DNA was measured using immunofluorescence. The adjusted odds ratio (OR) and 95% confidence interval (CI) were estimated using unconditional logistic regression. Our results revealed a statistically significant difference between the cases and controls in both genotypic distribution (P<0.001) and allelic frequency (P = 0.021) only for the NOS3 rs1799983 SNP. Multivariate logistic regression analyses revealed that rs1799983 was associated with a borderline significantly increased risk of male infertility (GT vs. GG: adjusted OR = 1.30, 95% CI: 1.00-1.70; GT+TT vs. GG: adjusted OR = 1.34, 95% CI: 1.03-1.74; P trend = 0.020). Moreover, NOS3 rs1799983 was positively associated with higher levels of sperm DNA fragmentation (β = 0.223, P = 0.044). However, the other 4 polymorphisms (NOS1 rs2682826, NOS1 rs1047735, NOS2 rs2297518, and NOS2 rs10459953) were not found to have any apparent relationships with male infertility risk. Of five NOS gene polymorphisms investigated in the present study, we found NOS3 rs1799983 might cause oxidative sperm DNA damage, thereby contributing to male infertility.


PAX8-positive Biphasic Synovial Sarcoma Expressing Hormonal Receptors.
PAX8, estrogen receptor-α (ERα) and progesterone receptor (PR) are markers usually expressed in neoplasms of müllerian origin. We report a subdiaphragmal mass in a 41-year-old woman corresponding to a malignant biphasic tumor with nests of epithelial-like cells forming variably sized cyst-like spaces alternating with spindle cells forming intersecting fascicles. The later were juxtaposed to coalescent densely cellular nodules of spindle cells with appreciable cytologic atypia and mitotic counts up to 30/10 high-power fields. The tumor cells were AE1/AE3, EMA, ERG, ERα, PR, and PAX8 positive whereas spindle cells showed reduced immunopositivity for these markers, especially marked in coalescent nodular areas, with notable exception of PAX8, which was diffuse and strongly positive. The possibility of an endometrioid carcinoma with spindle cells was considered by the referring pathologist, but fluorescent in situ hybridization showed rearrangement of SS18 gene in 48 of 50 tumor nuclei, rendering a diagnosis of biphasic synovial sarcoma, the first reported in the English literature to the best of our knowledge expressing PAX8, ERα, and PR. Further studies evaluating the expression of these markers in synovial sarcoma and other sarcomas are needed, as sometimes the findings may lead to misdiagnosis as other neoplasms including those of the female genital tract. Additional molecular tests may be helpful to determine the molecular mechanism of this aberrant immunoprofile, which could be directly or indirectly related to t(X:18).


Multi-Level Family Factors and Affective and Behavioral Symptoms of Oppositional Defiant Disorder in Chinese Children.
Given the important role of family environment in children's psychological development, the objective of this study was to examine the linkages between family factors at the whole, dyadic, and individual levels and two dimensions (affective and behavioral) of Oppositional Defiant Disorder (ODD) symptoms in Chinese children. Participants comprised of 80 father-child dyads and 169 mother-child dyads from families with ODD children. The results indicated that multilevel family factors were differently associated with children's affective and behavioral ODD symptoms. All the family factors at the dyadic and individual levels were significantly associated with child affective ODD symptoms. However, only the most proximal factors (parent-child relationship and child emotion regulation, which were directly related to child) were significantly related to child behavioral ODD symptoms. The present study extends the current knowledge regarding the relationships between family factors and two dimensions of child ODD symptoms by testing the comprehensive multilevel family factors model. This study also recommends that future interventions for ODD children should consider the multi-level family factors to enhance intervention efficacy.


Hysteresis in motor and language production.
Hysteresis in motor planning and syntactic priming in language planning refer to the influence of prior production history on current production behaviour. Computational efficiency accounts of action hysteresis and theoretical accounts of syntactic priming both argue that reusing an existing plan is less costly than generating a novel plan. Despite these similarities across motor and language frameworks, research on planning in these domains has largely been conducted independently. The current study adapted an existing language paradigm to mirror the incremental nature of a manual motor task to investigate the presence of parallel hysteresis effects across domains. We observed asymmetries in production choice for both the motor and language tasks that resulted from the influence of prior history. Furthermore, these hysteresis effects were more exaggerated for subordinate production forms implicating an inverse preference effect that spanned domain. Consistent with computational efficiency accounts, across both task participants exhibited reaction time savings on trials in which they reused a recent production choice. Together, these findings lend support to the broader notion that there are common production biases that span both motor and language domains.


The estimated prevalence of hypospadias in Hokkaido, Japan.
Hypospadias is one of the most common congenital anomalies in the world. Recently, increases in the prevalence of hypospadias have been reported in various countries including Japan. In this study, we examined whether the prevalence of hypospadias in Hokkaido, Japan, increased or not, using standardized diagnostic criteria. We also investigated the degree of its severity. We calculated prevalence of hypospadias using hospital records of hypospadias repair in Hokkaido. The prevalence from 1985 through 1997 by dividing the number of patients obtained from hospital records by the number of births. The average prevalence of hypospadias in Hokkaido was 3.9 per 10,000 births, and did not significantly change (p=0.7). The average proportions of distal, proximal and chordee alone were 56.7%, 39.6% and 3.7%, respectively. The decrease in the proportion of the proximal type was statistically significant (p=0.05) for the entire time period, whereas the proportion of the distal type did not have a significant upward trend for the observed 13 years (p=0.1). No significant changes in the prevalence of hypospadias existed in Hokkaido.


Silver nanoparticles: behaviour and effects in the aquatic environment.
This review summarises and evaluates the present knowledge on the behaviour, the biological effects and the routes of uptake of silver nanoparticles (Ag NPs) to organisms, with considerations on the nanoparticle physicochemistry in the ecotoxicity testing systems used. Different types of Ag NP syntheses, characterisation techniques and predicted current and future concentrations in the environment are also outlined. Rapid progress in this area has been made over the last few years, but there is still a critical lack of understanding of the need for characterisation and synthesis in environmental and ecotoxicological studies. Concentration and form of nanomaterials in the environment are difficult to quantify and methodological progress is needed, although sophisticated exposure models show that predicted environmental concentrations (PECs) for Ag NPs in different environmental compartments are at the range of ng L(-1) to mg kg(-1). The ecotoxicological literature shows that concentrations of Ag NPs below the current and future PECs, as low as just a few ng L(-1), can affect prokaryotes, invertebrates and fish indicating a significant potential, though poorly characterised, risk to the environment. Mechanisms of toxicity are still poorly understood although it seems clear that in some cases nanoscale specific properties may cause biouptake and toxicity over and above that caused by the dissolved Ag ion. This review concludes with a set of recommendations for the advancement of understanding of the role of nanoscale silver in environmental and ecotoxicological research.


Time-resolved momentum imaging system for molecular dynamics studies using a tabletop ultrafast extreme-ultraviolet light source.
We describe a momentum imaging setup for direct time-resolved studies of ionization-induced molecular dynamics. This system uses a tabletop ultrafast extreme-ultraviolet (EUV) light source based on high harmonic upconversion of a femtosecond laser. The high photon energy (around 42 eV) allows access to inner-valence states of a variety of small molecules via single photon excitation, while the sub--10-fs pulse duration makes it possible to follow the resulting dynamics in real time. To obtain a complete picture of molecular dynamics following EUV induced photofragmentation, we apply the versatile cold target recoil ion momentum spectroscopy reaction microscope technique, which makes use of coincident three-dimensional momentum imaging of fragments resulting from photoexcitation. This system is capable of pump-probe spectroscopy by using a combination of EUV and IR laser pulses with either beam as a pump or probe pulse. We report several experiments performed using this system.


[A clinical study of chronic disseminated candidiasis in patients with acute leukemia].
To deepen the understanding of chronic disseminated candidiasis (CDC) in patients with acute leukemia (AL). CDC was investigated in 119 AL patients who received induction chemotherapy from August 2004 to May 2005. Clinical manifestations, laboratory tests, imaging modalities, diagnosis and treatment were investigated retrospectively. Three patients (2.5%) were identified to be suffering from CDC. All the three patients had an absolute neutrophil count (ANC) <0. 5 x 10(9)/L for more than 15 days. Two patients had normal ANC when they were diagnosed to have CDC. The common manifestations in these three patients were persistent fever, splenohepatomegalia and percussion pain in hepatic region. Meanwhile, 2 of them were accompanied with cough, expectoration and dyspnoea. The abnormal laboratory test observed during the course of infection in two of them was increase of alkaline phosphatase. Computed tomography scan showed multiple hypodense lesions in the liver and spleen in all the three patients; two of them showed multiple nodular patchy shadows in lungs. Nuclear magnetic resonance imaging showed multiple abnormal signal in liver, spleen and kidneys in one of the patients. Two patients had positive bleed fungal cultures and histologic examination in one of the patients were positive for Candida tropicalis. Two patients received amphotericin B therapy empirically, but it was replaced by amphotericin B colloid dispersion (ABCD) later in one and combined with voriconazole in another because of unresponsiveness to the drug. One patient took a favorable turn after receiving ABCD therapy for 45 d, which was replaced by voriconazole because of the emergence of fever after discontinuation of ABCD. All the three patients received further chemotherapy smoothly after the diagnosis of CDC. The diagnosis of CDC remains difficult. Fungal blood cultures and histologic examination have been considered in many studies as the golden standard for the diagnosis of CDC. Amphotericin B is the cornerstone of treatment in patients with CDC and lipid formulations of amphotericin B can be used in CDC patients who are intolerant of or refractory to conventional amphotericin B. Voriconazole has a favorable response for refractory/relapse patients and could be used for second line treatment. The development of CDC in patients with acute leukemia does not preclude further chemotherapy.


Combined effect of predatory zooplankton and allelopathic aquatic macrophytes on algal suppression.
The present study evaluated the combined effects of four typical predatory zooplankton and allelopathic aquatic macrophytes on algal control in a microcosm system. It would determine the effects of diverse species and biological restoration on the growth of harmful water-bloom microalgae in great lakes polluted by excess nutrients. It was found that the mixtures of each zooplankton and the floating plant Nymphoides peltatum had stronger inhibitory effects on harmful water-bloom microalgae than the individual species in clean or eutrophic water bodies. In addition, a community of four zooplankton types had a synergistic effect on algal inhibition. Algal suppression by the zooplankton community was enhanced significantly when the macrophyte was co-cultured in the microcosm. Furthermore, Chlorella pyrenoidosa was more susceptible than Microcystis aeruginosa when exposed to grazing by zooplankton and the allelopathic potential of the macrophyte. Algal inhibition was also weaker in eutrophic conditions compared with the control. These findings indicate that diverse species may enhance algal inhibition. Therefore, it is necessary to restore biological diversity and rebuild an ecologically balanced food chain or web to facilitate the control of harmful algal blooms in eutrophic lakes.


Exploring the Molecular Basis of Qo bc1 Complex Inhibitors Activity to Find Novel Antimalarials Hits.
Cytochrome bc1 complex is a crucial element in the mitochondrial respiratory chain, being indispensable for the survival of several species of Plasmodia that cause malaria and, therefore, it is a promising target for antimalarial drug development. We report a molecular docking study building on the most recently obtained X-ray structure of the Saccharomyces cerevisiae bc1 complex (PDB code: 3CX5) using several reported inhibitors with experimentally determined IC50 values against the Plasmodium falciparum bc1 complex. We produced a molecular docking model that correlated the calculated binding free energy with the experimental inhibitory activity of each compound. This Qo model was used to search the drug-like database included in the MOE package for novel potential bc1 complex inhibitors. Twenty three compounds were chosen to be tested for their antimalarial activity and four of these compounds demonstrated activity against the chloroquine-resistant W2 strain of P. falciparum. The most active compounds were also active against the atovaquone-resistant P. falciparum FCR3 strain and S. cerevisiae. Our study suggests the validity of the yeast bc1 complex structure as a model for the discovery of new antimalarial hits.


Customized and non-customized live-born birth-weight curves of single and uncomplicated pregnancies from the Burgundy perinatal network. Part I - methodology.
To establish non-customized and customized birth-weight curves of single and uncomplicated pregnancies according to gestational age. We used data for 64,173 mother-infants pairs from the Burgundy perinatal network database (France) over the period 2005-2013. A validated procedure was used to link mothers with their newborns, and maternal and fetal pathologies likely to affect birth weight were excluded. Multiple regression analysis with covariate selection was used to build a customized growth curve with maternal and fetal parameters. Using this methodology, three different curves were generated: an unadjusted curve for birth weight, named B0, an curve adjusted for fetal gender, named B1 and a curve adjusted for fetal and maternal parameters (fetal gender, maternal height, weight and parity), named B2. We present curves showing an original distribution of birth weights for the French population in order to improve the diagnosis of small for gestational age. These curves are not based on the Gardosi in utero growth model but on actual birth weights, thus limiting bias. Nevertheless, the minimum gestational age was 25weeks as there was an insufficient number of live-borns in small gestational ages.


Lgr5-expressing chief cells drive epithelial regeneration and cancer in the oxyntic stomach.
The daily renewal of the corpus epithelium is fuelled by adult stem cells residing within tubular glands, but the identity of these stem cells remains controversial. Lgr5 marks homeostatic stem cells and 'reserve' stem cells in multiple tissues. Here, we report Lgr5 expression in a subpopulation of chief cells in mouse and human corpus glands. Using a non-variegated Lgr5-2A-CreERT2 mouse model, we show by lineage tracing that Lgr5-expressing chief cells do not behave as corpus stem cells during homeostasis, but are recruited to function as stem cells to effect epithelial renewal following injury by activating Wnt signalling. Ablation of Lgr5+ cells severely impairs epithelial homeostasis in the corpus, indicating an essential role for these Lgr5+ cells in maintaining the homeostatic stem cell pool. We additionally define Lgr5+ chief cells as a major cell-of-origin of gastric cancer. These findings reveal clinically relevant insights into homeostasis, repair and cancer in the corpus.


Influence of Optic Nerve Appearance on Visual Outcome in Pediatric Idiopathic Intracranial Hypertension.
To determine whether optic disc hemorrhages (ODH) and cotton wool spots (CWS) at presentation are associated with worse visual outcomes in pediatric patients with idiopathic intracranial hypertension (IIH). Retrospective institutional review of 100 eyes of 50 consecutive pediatric IIH patients (aged 16 years or less) who had baseline optic disc photographs before or within 30 days of their diagnostic lumbar puncture and initiation of medical treatment. Optic disc photographs were independently graded by three ophthalmologists in a standardized manner. Visual function was assessed using visual acuity (VA) and visual field grade (VFG). At least one ODH was found in 41% of eyes, at least one CWS was found in 27% of eyes, and 20% of eyes had both ODH and CWS. At presentation, Frisén grade was associated with the presence of CWS (p = 0.013) and showed no association with ODH (p = 0.060). When controlling for Frisén grade, ODH and CWS were not associated with worse VA or VFG at final follow-up. Severe ODH were associated with worse VA and VFG at presentation (p < 0.03), but not at final follow-up. Severe CWS at presentation was strongly associated with a worse Humphrey mean deviation of 5.0 dB (95% confidence interval 1.6-8.3) at final follow-up (p = 0.002). When controlling for the severity of papilledema, ODH do not provide any additional prognostic value in pediatric IIH patients. Frisén grade and severe CWS at presentation were independently associated with worse visual outcomes at the final follow-up.


Adaptive Genetic Differentiation and Solar Radiation in Wild Emmer Wheat, Triticum dicoccoides.
Microgeographic studies of molecular markers could reveal the nature and dynamics of genetic diversity and the evolutionary driving forces shaping evolution. The microclimatic genetic divergence of wild emmer wheat associated with solar radiation was investigated, in the present study, using multiple types of molecular markers including allozyme, amplified polymorphic DNA (RAPD), simple sequence repeat (SSR), and single nucleotide polymorphisms (SNP). The studies included two climatic microniches: (1) sunny between oak trees; and (2) shady under the canopies of oak trees. All four types of markers showed a similar microniche tendency of genetic variance, i.e., lower in the shady than in the sunny niche. Significant genetic divergence at some loci including allozyme, RAPD, SSR, and SNP was detected between the two climatic microniches, and also, the observed genetic differentiation is mainly due to natural selection. Based on different FST outlier detection algorithms, there were 21 candidate loci subjected to positive selection. Importantly, most of the identified candidate loci were mapped in the selection "hot spots" of wheat genome. The present work implies that microclimatic selection appears to play an important role either in the protein-coding region or in the non-coding region of wheat genomes, and hence, highlights the evolutionary theory of natural selection.


The Leaves of Broussonetia kazinoki Siebold Inhibit Atopic Dermatitis-Like Response on Mite Allergen-Treated Nc/Nga Mice.
Broussonetia kazinoki Siebold. (B. kazinoki) has long been used in the manufacture of paper in Asian countries. Although B. kazinoki leaves (BK) have been employed in dermatological therapy, use of BK has not been tested in patients with atopic dermatitis (AD). Using Nc/Nga mice, which are genetically predisposed to develop AD-like skin lesions, we confirmed the efficacy of BK in AD treatment. BK extract was applied topically to Dermatophagoides farinae-induced AD-like lesions in Nc/Nga mice, and the effects were assessed both clinically and by measuring skin thickness on the back and ears. We measured the effects of BK extract on plasma levels of IgE and IL-4. We also measured the ability of BK extract to inhibit the secretion of hTARC in HaCaT cells after stimulation by TNF-α and IFN-γ. We found that BK extract significantly reduced ear and dorsal skin thickness and the clinical signs of AD, as well as significantly down-regulating the plasma levels of IgE and IL-4 (p<0.01 for each comparison). Moreover, 500 μg/mL of BK extract inhibited hTARC secretion in HaCaT cells by activated TNF-α/IFN-γ by about 87%. These findings suggest that topical application of BK extract has excellent potential in the treatment of AD.


Frequent allelic losses on chromosomes 2q, 18q, and 22q in advanced non-small cell lung carcinoma.
Although it is widely accepted that tumor suppressor genes play an important role in the genesis and progression of human cancer, little is known about genetic events that accumulate during multistage lung carcinogenesis. Thus, to determine a subset of tumor suppressor genes that are involved in the genesis and progression of non-small cell lung carcinoma (NSCLC), 22 brain metastases and 23 stage I primary lung tumors were examined for allelic losses at 40 loci on 10 chromosomes including the loci of 5 tumor suppressor genes, APC, WT1, RB, p53, and DCC. The incidence of allelic losses on chromosomes 3p, 13q, and 17p was high (> 60%) in both primary tumors and brain metastases. In brain metastases, a high incidence of allelic losses (> 60%) was also observed at loci on chromosomes 2q, 18q, and 22q, and the incidence of allelic losses on these chromosomes in brain metastases was significantly higher than that in primary tumors (P < 0.05). In two cases of brain metastases with corresponding primary lung tumors, sequential accumulation of allelic losses during progression of primary lung tumors was observed on several chromosomes including chromosomes 2q and 18q. These results indicate that, besides loss of heterozygosity for chromosomes 3p, 13q, and 17p, loss of heterozygosity for chromosomes 2q, 18q, and 22q also occurs frequently in advanced NSCLCS. Thus, it is possible that loss of heterozygosity on chromosomes 2q, 18q, and 22q occurs late in the progression of NSCLC and/or causes phenotypic alterations of NSCLC cells into more aggressive ones.


Estimating paid and unpaid hours of personal assistance services in activities of daily living provided to adults living at home.
To estimate the total hours of paid and unpaid personal assistance of daily living provided to adults living at home in the United States using nationally representative household survey data. The Disability Followback Survey of the National Health Interview Survey on Disability (NHIS-D) conducted from 1994 to 1997. Data were obtained on persons receiving help with up to 5 ADLs and 10 IADLs, for up to 4 helpers, including the activities they helped with, whether the helper was paid or not, and the number of hours of help provided in the two weeks prior to the survey. The sample consists of 8,471 household-resident adults ages 18 and older receiving help with personal assistance. About 22 percent of the sample has missing data on hours, which we impute by multiple regression models using demographic, ADL, and IADL variables. We estimate that 13.2 million noninstitutionalized adults receive an average of 31.4 hours per week of personal assistance in ADLs and IADLs per week, with 3.2 million people receiving an average of 17.6 hours of paid help and 11.7 million receiving an average of 30.7 hours of unpaid help. More persons ages 18-64 received help than those ages 65 and older (6.9 versus 6.2 million), but working-age recipients had fewer hours (27.4 versus 35.9) per week, due in part to less severe levels of disability. Personal assistance provided to adults with disabilities amounts to 21.5 billion hours of help per year, with an economic value in 1996 approaching $200 billion. Only 16 percent of this total is paid, representing $32 billion in home health services spent annually. This study, the first to estimate hours of assistance for both working-age and older adults, documents that older persons are more likely to receive paid personal assistance, while working-age people rely to a greater extent on unpaid help. This study begins to articulate the division of labor in the provision of personal assistance. Estimates of paid and unpaid hours of help by number of ADLs should inform policy concerning eligibility boundaries in long term care.


Where does the electron go? The nature of ortho/para and meta group directing in electrophilic aromatic substitution.
Electrophilic aromatic substitution as one of the most fundamental chemical processes is affected by atoms or groups already attached to the aromatic ring. The groups that promote substitution at the ortho/para or meta positions are, respectively, called ortho/para and meta directing groups, which are often characterized by their capability to donate electrons to or withdraw electrons from the ring. Though resonance and inductive effects have been employed in textbooks to explain this phenomenon, no satisfactory quantitative interpretation is available in the literature. Here, based on the theoretical framework we recently established in density functional reactivity theory (DFRT), where electrophilicity and nucleophilicity are simultaneously quantified by the Hirshfeld charge, the nature of ortho/para and meta group directing is systematically investigated for a total of 85 systems. We find that regioselectivity of electrophilic attacks is determined by the Hirshfeld charge distribution on the aromatic ring. Ortho/para directing groups have most negative charges on the ortho/para positions, while meta directing groups often possess the largest negative charge on the meta position. Our results do not support that ortho/para directing groups are electron donors and meta directing groups are electron acceptors. Most neutral species we studied here are electron withdrawal in nature. Anionic systems are always electron donors. There are also electron donors serving as meta directing groups. We predicted ortho/para and meta group directing behaviors for a list of groups whose regioselectivity is previously unknown. In addition, strong linear correlations between the Hirshfeld charge and the highest occupied molecular orbital have been observed, providing the first link between the frontier molecular orbital theory and DFRT.


Factors influencing uptake, continuation, and discontinuation of oral PrEP among clients at sex worker and MSM facilities in South Africa.
South Africa became the first country in Africa to introduce oral PrEP in June 2016. The National Department of Health has used a phased approach to rollout, allowing for a dynamic learn-and-adapt process which will lead ultimately to scale-up. Phased rollout began with provision of oral PrEP at facilities providing services to sex workers in 2016 and was expanded in 2017, first to facilities providing services to MSM and then to students at selected university campus clinics, followed by provision at primary health care facilities. Programmatic data shows variability in initiation and continuation between these populations. This study examines factors related to PrEP initiation, continuation, and discontinuation at facilities providing services to sex workers and MSM during the national PrEP rollout. A cross-sectional survey was administered September 2017-January 2018 among clients (ages 18-62 and providers at 9 facilities implementing oral PrEP in South Africa, followed by in-depth interviews. The client survey captured PrEP initiation, continuation and discontinuation. Analysis was performed in STATA 13 for survey data and thematic analysis was performed in NViVO 11 for in-depth interview data. 299 clients (203 from sex worker facilities, 96 from MSM facilities) participated in the survey and additionally, in-depth interviews were conducted with 29 clients. Participants self-identified as either current users (n = 94; 36.2%), past users (n = 80; 30.8%) and never users of PrEP (n = 86; 33.1%). Participants who had never used PrEP either cited not being offered PrEP by a provider (57%, n = 49) or declining PrEP (43%, n = 37) as reasons for lack of uptake. The primary reason for declining to use oral PrEP was fear of side effects (41.7%, n = 15). The primary reasons for initiating and continuing on oral PrEP were all related to perceived risk associated with sexual activity. The majority of participants (87.9%, n = 153) also noted that printed IEC materials influenced their decision to initiate PrEP. Qualitative data suggested that several clients initiated on PrEP because they wanted additional protection beyond using condoms due to challenges such as partners refusing to use condoms, having partners with unknown HIV status, having multiple partners, involvement in sex work, or having a partner living with HIV. The majority (73.8%, n = 59) of participants who discontinued oral PrEP cited side effects as the primary reason for discontinuation, followed by feeling stigmatized (18.8%, n = 15). This study provides valuable insights on early rollout of PrEP of how clients perceive oral PrEP and where to target efforts to improve the uptake of this highly effective HIV prevention product. By identifying strengths and areas for improvement, the ACCESS study has generated evidence that can be used to guide high quality scale-up in South Africa and may be instructive for other countries' efforts to expand quality access to oral PrEP.


Development of daytime somnolence over time in Parkinson's disease.
The authors examined the development over time of excessive daytime sleepiness (EDS) in patients with PD by evaluating EDS among 142 patients in 1993 and 4 years later. Eleven patients were diagnosed with EDS in 1993. In all of these patients, EDS persisted 4 years later. During follow-up, 30 new patients had EDS (6% new patients per year). In 1997, 29% of the patients with PD had EDS. The development of EDS correlated with more advanced disease and dementia.


A decision rule to aid selection of patients with abdominal sepsis requiring a relaparotomy.
Accurate and timely identification of patients in need of a relaparotomy is challenging since there are no readily available strongholds. The aim of this study is to develop a prediction model to aid the decision-making process in whom to perform a relaparotomy. Data from a randomized trial comparing surgical strategies for relaparotomy were used. Variables were selected based on previous reports and common clinical sense and screened in a univariable regression analysis to identify those associated with the need for relaparotomy. Variables with the strongest association were considered for the prediction model which was constructed after backward elimination in a multivariable regression analysis. The discriminatory capacity of the model was expressed with the area under the curve (AUC). A cut-off analysis was performed to illustrate the consequences in clinical practice. One hundred and eighty-two patients were included; 46 were considered cases requiring a relaparotomy. A prediction model was build containing 6 variables. This final model had an AUC of 0.80 indicating good discriminatory capacity. However, acceptable sensitivity would require a low threshold for relaparotomy leading to an unacceptable rate of negative relaparotomies (63%). Therefore, the prediction model was incorporated in a decision rule were the interval until re-assessment and the use of Computed Tomography are related to the outcome of the model. To construct a prediction model that will provide a definite answer whether or not to perform a relaparotomy seems a utopia. However, our prediction model can be used to stratify patients on their underlying risk and could guide further monitoring of patients with abdominal sepsis in order to identify patients with suspected ongoing peritonitis in a timely fashion.


Significant second-harmonic generation and bulk photovoltaic effect in trigonal selenium and tellurium chains.
One-dimensional (1D) selenium and tellurium crystalize in helical chainlike structures and thus exhibit fascinating properties. By performing first-principles calculations, we have researched the linear and nonlinear optical (NLO) properties of 1D Se and Te, and find that both systems exhibit pronounced NLO responses. In particular, 1D Se is found to possess a large second-harmonic generation coefficient with the χ value being up to 7 times larger than that of GaN, and is even several times larger than that of the bulk counterpart. On the other hand, 1D Te also produces significant NLO susceptibility χ which exceeds that of bulk GaN by 5 times. Furthermore, 1D Te is shown to possess a prominent linear electro-optic coefficient rxxx(0). In particular, the Te chain exhibits a large shift current response and the maximum is twice as large as the maximal photovoltaic responses obtained from BaTiO3. Therefore, 1D Se and Te may find potential applications in solar energy conversion, electro-optical switches, and so on. Finally, the much stronger NLO effects of 1D Se and Te are attributed to their one-dimensional structures with high anisotropy, strong covalent bonding and lone-pair electrons. These findings will contribute further to experimental studies and the search for excellent materials with large NLO effects.


A non-mutated TROP2 fingerprint in cancer genetics.
The advent of high throughput DNA sequencing is providing massive amounts of tumor-associated mutation data. Implicit in these analyses is the assumption that, by acquiring a series of hallmark changes, normal cells evolve along a neoplastic path. However, the lack of correlation between cancer risk and global exposure to mutagenic factors provides arguments against this model. This suggested that additional, non-mutagenic factors are at work in cancer development. A candidate determinant is TROP2, that stands out for its expression in the majority of solid tumors in human, for its impact on the prognosis of most solid cancers and for its role as driver of cancer growth and metastatic diffusion, through overexpression as a wild-type form. The Trop-2 signaling network encompasses CREB1, Jun, NF-κB, Rb, STAT1 and STAT3, through induction of cyclin D1 and MAPK/ERK. Notably, Trop-2-driven pathways vastly overlap with those activated by most functionally relevant/most frequently mutated RAS and TP53, and are co-expressed in a large fraction of individual tumor cases, suggesting functional overlap. Mutated Ras was shown to synergize with the TROP2-CYCLIND1 mRNA chimera in transforming primary cells into tumorigenic ones. Genomic loss of TROP2 was found to promote carcinogenesis in squamous cell carcinomas through modulation of Src and mutated Ras pathways. DNA methylation and TP53 status were shown to cause genome instability and TROP gene amplification, together with Trop-2 protein overexpression. These findings suggest that mutagenic and the TROP2 non-mutagenic pathways deeply intertwine in driving transformed cell growth and malignant progression of solid cancers.


The role of histamine H-receptors in the anaphylactic histamine release from human basophilic leukocytes.
The effect of two recently synthetized selective histamine H2-receptor agonists on anaphylactic histamine release from human basophilic leukocytes was investigated. It was found that both agonists tested, partially inhibited histamine release induced either by antigen or by human anti-IgE. Cimetidine, the histamine H2-receptor antagonist, generally antagonized this effect. It is concluded that anaphylactic basophil histamine release can be modulated by stimulation of histamine H2-receptors.


Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension)
Although the benefits of antihypertensive treatment in "young" elderly (under 70 years) hypertensive patients are well established, the value of treatment in older patients (70-84 years) is less clear. The Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) was a prospective, randomised, double-blind, intervention study set up to compare the effects of active antihypertensive therapy (three beta-blockers and one diuretic) and placebo on the frequency of fatal and non-fatal stroke and myocardial infarction and other cardiovascular death in hypertensive Swedish men and women aged 70-84 years. We recruited 1627 patients at 116 health centres throughout Sweden, who were willing to participate, and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg, or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure. The total duration of the study was 65 months and the average time in the study was 25 months. 812 patients were randomly allocated active treatment and 815 placebo. The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint, death, or study termination was 19.5/8.1 mm Hg. Compared with placebo, active treatment significantly reduced the number of primary endpoints (94 vs 58; p = 0.0031) and stroke morbidity and mortality (53 vs 29; p = 0.0081). Although we did not set out to study an effect on total mortality, we also noted a significantly reduced number of deaths in the active treatment group (63 vs 36; p = 0.0079). The benefits of treatment were discernible up to age 84 years. We conclude that antihypertensive treatment in hypertensive men and women aged 70-84 confers highly significant and clinically relevant reductions in cardiovascular morbidity and mortality as well as in total mortality.


Effectiveness of an enhanced peer assessment program: introducing education into regulatory assessment.
The College of Physicians and Surgeons of Ontario developed an enhanced peer assessment (EPA), the goal of which was to provide participating physicians educational value by helping them identify specific learning needs and aligning the assessment process with the principles of continuing education and professional development. In this article, we examine the educational value of the EPA and whether physicians will change their practice as a result of the recommendations received during the assessment. A group of 41 randomly selected physicians (23 general or family practitioners, 7 obstetrician-gynecologists, and 11 general surgeons) agreed to participate in the EPA pilot. Nine experienced peer assessors were trained in the principles of knowledge translation and the use of practice resources (tool kits) and clinical practice guidelines. The EPA was evaluated through the use of a postassessment questionnaire and focus groups. The physicians felt that the EPA was fair and educationally valuable. Most focus group participants indicated that they implemented recommendations made by the assessor and made changes to some aspect of their practice. The physicians' suggestions for improvement included expanding the assessment beyond the current medical record review and interview format (eg, to include multisource feedback), having assessments occur at regular intervals (eg, every 5 to 10 years), and improving the administrative process by which physicians apply for educational credit for EPA activities. The EPA pilot study has demonstrated that providing detailed individualized feedback and optimizing the one-to-one interaction between assessors and physicians is a promising method for changing physician behavior. The college has started the process of aligning all its peer assessments with the principles of continuing professional development outlined in the EPA model.


Bottlenecks to clinical translation of direct brain-computer interfaces.
Despite several decades of research into novel brain-implantable devices to treat a range of diseases, only two-cochlear implants for sensorineural hearing loss and deep brain stimulation for movement disorders-have yielded any appreciable clinical benefit. Obstacles to translation include technical factors (e.g., signal loss due to gliosis or micromotion), lack of awareness of current clinical options for patients that the new therapy must outperform, traversing between federal and corporate funding needed to support clinical trials, and insufficient management expertise. This commentary reviews these obstacles preventing the translation of promising new neurotechnologies into clinical application and suggests some principles that interdisciplinary teams in academia and industry could adopt to enhance their chances of success.


Uniaxial alignment of triisopropylsilylethynyl pentacene via zone-casting technique.
Uniaxially aligned triisopropylsilylethynyl pentacene (TIPS-pentacene) crystals over a large area were fabricated using zone-casting technique. The array of TIPS-pentacene displayed a high orientation degree with a dichroic ratio (DR) of 0.80. The crystals were arranged with c axis perpendicular to the substrate and the long axis of the ribbon corresponded to the a axis of TIPS-pentacene. The properties of the solutions and the processing parameters were shown to influence the formation of the oriented TIPS-pentacene crystalline array. Solvent with a low boiling point (such as chloroform) favoured the orientation of the ribbon-like crystals. The concentration of the solution should be appropriate, ensuring the crystallization velocity of TIPS-pentacene matching with the receding of the meniscus. Besides, we proved that the casting speed should be large enough to induce a sufficient concentration gradient. The orientation mechanism of TIPS-pentacene was attributed to a synergy of the ordered nuclei and a match between the crystallization velocity and the casting speed. Field effect transistors (FETs) based on the oriented TIPS-pentacene crystalline array showed a mobility of 0.67 cm(2) V(-1) s(-1).


Fouling-resistant surfaces of tropical sea stars.
Qualitative evidence suggests sea stars are free of fouling organisms; however the presence of fouling-resistant surfaces of sea stars has not previously been documented. Field surveys were conducted in northern Queensland, Australia, during the wet and dry seasons and several tropical sea star species were examined for surface-associated micro- and macro-organisms. Mean bacterial abundances on seven sea star species were approximately 10(4) to 10(5) cells cm(-2) during both seasons. There were no consistent trends in bacterial abundances with season, species and aboral positions on sea star arms. No common generalist fouling organisms, such as algae, barnacles, serpulid polychaetes, bryozoans and ascidians, were found on any specimens of 12 sea star species. However, low numbers of parasitic and commensal macro-organisms were found on six sea star species. The gastropods Parvioris fulvescens, Asterolamia hians, Thyca (Granulithyca) nardoafrianti and Thyca crystallina were found exclusively on the sea stars Archaster typicus, Astropecten indicus, Nardoa pauciforis and Linckia laevigata, respectively. The shrimp Periclimenes soror was only found on Acanthaster planci, and the polychaete Ophiodromus sp. on A. typicus. The copepods Stellicola illgi and Paramolgus sp. were only found on L. laevigata and Echinaster luzonicus, respectively. As no common generalist fouling organisms were discovered, sea stars offer an excellent model to investigate the mechanisms driving fouling-resistant surfaces and the selective settlement of specialist invertebrates.


Resistance to highly virulent mouse hepatitis virus acquired by mice after low-virulence infection: enhanced antiviral activity of macrophages.
As early as 1 to 2 days after intranasal inoculation with a mouse hepatitis virus of low virulence, MHV-S, susceptible DDD mice became fully resistant to a normally lethal challenge with a highly virulent MHV-2. The resistance of MHV-S-pretreated mice was correlated with significantly decreased MHV-2 multiplication in the liver, spleen, and brain. Infection with MHV-S did not induce a high level of interferon in DDD mice, and no neutralizing antibody against MHV-2 was detected in the sera of mice until day 6 of MHV-S infection. The multiplication of MHV-2 was suppressed in peritoneal cells (PC) in vivo and peritoneal adherent cells (PAC) in vitro of MHV-S-pretreated mice was compared with those of normal mice. This suppression of virus multiplication was demonstrated in PAC collected during days 1 to 3 of infection but not in PAC collected from day 5 on. PC from MHV-S-pretreated mice were also suppressive to MHV-2 growth in DK cells as compared with PC from normal mice. By treatment of MHV-S-pretreated mice with silica, suppression of virus growth in the liver was partially diminished. These findings suggest that increased suppression of MHV-2 growth in PAC (mostly macrophages) of MHV-S-pretreated mice is responsible for resistance.


Pharmacological treatment of acute mania in psychiatric in-patients between 1994 and 2004.
In a cross-section approach we investigated prescription practice in acute mania in 63 German, Swiss and Austrian hospitals between 1994 and 2004. Our data were gathered from a large drug safety program (AMSP) within which on two reference days each year all administered drugs are recorded. For the present study, all cases with a primary diagnosis of acute euphoric mania (n=1291) or mixed-state mania (n=143) were identified. Prescription rates from two periods, 1994 to 1999 and 2000 to 2004, were compared. In euphoric mania, prescription of lithium decreased by about one-fifth (43.3% to 34.5%, p<0.01), while prescription of anticonvulsants increased by one-half (from 40.0% to 60.7%, p<0.001). Administration of atypical antipsychotics more than doubled (18.5% to 43.9%, p<0.001), while use of typical antipsychotics decreased significantly (56.9% to 27.8%, p<0.001). Overall prescription rates of antipsychotics (79.6% vs. 81.6%) and antidepressants (14.0% vs. 15.5%) remained stable, while administration of tranquilizers increased significantly (26.3% to 34.3%, p<0.01). In mixed-state mania, similar trends over time to those seen in euphoric mania were observed for lithium (43.2% to 33.3%), anticonvulsants (50.0% to 69.7%, p<0.05) and tranquilizers (22.7% to 40.4%). Prescription rates of antipsychotics slightly increased (63.6% to 72.7%), while prescription of antidepressants slightly decreased (54.5% to 46.5%). Polypharmacy was a common phenomenon: patients with euphoric mania were treated with a mean number of 2.9+/-1.2 psychotropic agents, and patients with mixed-state mania with 3.3+/-1.5 psychotropic agents. Both groups showed a significant increase over time. Second-generation atypical antipsychotics were adopted quite rapidly for the treatment of acute mania considering the availability of the scientific evidence at that time. Off-label use was a common phenomenon. Deviations from recommended guidelines were found mainly in the use of antidepressant and antipsychotic drugs both in mixed-state and euphoric mania. Naturalistic prescription studies like this may encourage a critical scrutiny of clinical treatment habits and may also drive further research thus moderating potential differences between evidence-based knowledge and everyday clinical practice.


Immunoblotting PKC-delta: a cautionary note from the bench.
Antibodies that specifically recognize signaling proteins (or individual phosphorylation events at specific residues in proteins of interest) have become important tools in the study of signaling pathways. However, the recognition properties of many commercially available antibodies have not been fully characterized. In the course of studies exploring PKC-delta phosphorylation mechanisms in cardiomyocytes, we have demonstrated that a BD Transduction Laboratories anti-PKC-delta MAb (generally viewed as an anti-PKC-delta protein antibody) recognizes PKC-delta in resting, but not in PMA-treated, cardiomyocytes. The observations that PKC-delta immunoreactivity is preserved when cultures are treated with PMA in the presence of a the PKC inhibitor GF-109203X and that PKC-delta immunoreactivity is restored by in vitro acid phosphatase treatment indicate that the epitope recognized by the BD Transduction Laboratories anti-PKC-delta MAb is masked by phosphorylation. The BD Transduction Laboratories MAb is poorly suited for studies that compare PKC-delta expression in resting and agonist-activated samples (or in studies of the relationship between PKC-delta phosphorylation and PKC-delta downregulation) because it artifactually displays PKC-delta phosphorylation as a decline in total PKC-delta protein. Other studies have shown that two anti-PKC-delta-pY(311) antibodies (manufactured by Cell Signaling Technology, Beverly, MA, and BioSource International, Camarillo, CA, respectively) specifically recognize stimulus-induced changes in PKC-delta-Y(311) phosphorylation on the endogenous PKC-delta enzyme, but the Cell Signaling Technology anti-PKC-delta-pY(311) antibody provides a better measure of Y(311) phosphorylation in overexpressed PKC-delta. Collectively, these studies have identified features of anti-PKC-delta antibodies that affect the interpretation of immunoblot analysis experiments. These findings related to PKC-delta may be symptomatic of a more pervasive feature of immunoblot analysis studies of phosphoproteins in general.


ADEPTUS: a discovery tool for disease prediction, enrichment and network analysis based on profiles from many diseases.
Large-scale publicly available genomic data on many disease phenotypes could improve our understanding of the molecular basis of disease. Tools that undertake this challenge by jointly analyzing multiple phenotypes are needed. ADEPTUS is a web-tool that enables various functional genomics analyses based on a high-quality curated database spanning >38, 000 gene expression profiles and >100 diseases. It offers four types of analysis. (i) For a gene list provided by the user it computes disease ontology (DO), pathway, and gene ontology (GO) enrichment and displays the genes as a network. (ii) For a given disease, it enables exploration of drug repurposing by creating a gene network summarizing the genomic events in it. (iii) For a gene of interest, it generates a report summarizing its behavior across several studies. (iv) It can predict the tissue of origin and the disease of a sample based on its gene expression or its somatic mutation profile. Such analyses open novel ways to understand new datasets and to predict primary site of cancer. Data and tool: http://adeptus.cs.tau.ac.il/home Analyses: Supplementary Material. firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


The tyrosine kinase inhibitors effects on metastatic tumor graft in the chick chorioallantoic membrane assay.
Due to its heterogeneous nature, pancreatic cancer has a higher incidence and a clinical treatment failure. In this study, we present the effects of Avastin, Rapamycin and their combination on the pancreatic liver metastatic human tumor graft in the chick chorioallantoic membrane (CAM) assay. We conducted this study with 33 fertilized chicken eggs, incubated at 37°C, divided into three working groups: control (three eggs), first (10 eggs), second (10 eggs), and third group (10 eggs). A cell suspensions derived from human liver metastasis of pancreatic tumor were implanted on the CAM, in the ring. First group was treated with 2 μL Avastin (Bevacizumab 25 mg÷mL), the second with Rapamycin and the third with Avastin and Rapamycin combination on days 10, 12, 14 of incubation. The immunohistochemical techniques using vascular endothelial growth factor A (VEGFA), CD34, podoplanin, platelet-derived growth factor subunit A (PDGFA) and epidermal growth factor receptor (EGFR) as primaries antibodies were performed on metastatic tumor and metastatic tumor graft. Our results showed that the unique treatment with Avastin gave rise to metastases on CAM xenograft, due likely to inflammatory infiltrate and vascular remodeling. The lowest immunoexpression of CD34, podoplanin, PDGFA, EGFR has been noticed in the Rapamycin-treated group without important differences correlated to dosage and time. In the third group, decreased value was found for PDGFA only. The periphery of the tumor graft malignant cells intensely expressed VEGFA, podoplanin and EGFR. The inhibitory therapy with mechanistic target of Rapamycin (mTOR) and Avastin may favor the epithelial to mesenchymal transition by podoplanin and phosphatase and tensin homolog (PTEN) pathways in liver metastasis pancreatic graft to CAM.


TARGETS OF SEXUAL SELECTION: SONG AND PLUMAGE OF WOOD WARBLERS.
Extant hypotheses predict that, in the face of sexual selection, avian song and plumage may evolve in a concerted fashion, in an antagonistic fashion, or in ways unrelated to each other. To test these ideas regarding which traits sexual selection targets, and the consequences for other traits, we analyzed patterns of song complexity and plumage dimorphism in 56 species of wood warblers (Parulinae). Overall, males of more dimorphic species sang shorter songs more often, but did not have more complex songs. However, when monomorphic species were excluded from the analysis, we found that the total time spent singing and repertoire size increased with plumage dimorphism. Monomorphic species are predominantly ground-nesters and the greater risk of nest predation for these species may constrain males from becoming more visually conspicuous. Thus, sexual selection may have been restricted to targeting song in these species. Even though song may have been the only target of sexual selection in ground-nesting species, overall, song in those species is not more complex than in species that nest above the ground. We propose that traits targeted by sexual selection evolve in concert, except when constrained by some ecological factor.


Current palliative modalities for esophageal carcinoma. Clinical review.
Esophageal carcinoma is often advanced at diagnosis, and management consequently can only be palliative, with relief of dysphagia and its consequences as the primary aim. The various methods for palliation are reviewed and their indications, advantages and drawbacks are discussed. If resection of the tumor is not feasible, YAG laser therapy seems to be the palliative method of choice in malignant dysphagia.


An infant with glutaric aciduria type IIc diagnosed with a novel mutation.
Işıkay S, Yaman A, Ceylaner S. An infant with glutaric aciduria type IIc diagnosed with a novel mutation. Turk J Pediatr 2017; 59: 315-317. Glutaric aciduria type II is a rare inborn error of metabolism. The clinical picture is highly variable with symptoms ranging from acute metabolic decompensations to chronic, mainly muscular problems or even asymptomatic cases. Herein we described a 7-month-old female patient presented with respiratory failure and diagnosed with glutaric aciduria type II via whole exome sequencing that exhibited one known and a novel mutation. Her blood and urine analyses were all normal. After the diagnosis, dramatic and sustained improvement on a low-fat, low-protein, and high-carbohydrate diet supplemented with oral riboflavin and carnitine was determined. In especially hypotonic patients with unknown etiologies, though the blood and urine analyses are normal, glutaric aciduria type II should also be kept in mind and genetic tests may be required for the diagnosis.


Digital filtering of auditory evoked potentials.
Digital filters have been proposed by many authors for analysis and enhancement of the auditory brain stem response and related potentials. Because these techniques are unfamiliar to many, and require attention to underlying assumptions, an overview of the field is presented, with emphasis on limitations and risks of each method. Topics include Fourier transforms, finite impulse response (convolutional) filters, and infinite impulse response (recursive) filters.


Hypophosphatemia: nutritional status, body composition, and mortality in hemodialysis patients.
The aim of the present study was to investigate the relationship between serum phosphate levels, clinical parameters, body composition, and mortality. Multicenter longitudinal observational study of a cohort of 3552 patients in hemodialysis (HD) from 34 Nephrocare dialysis units in Portugal with 24 months of follow-up. Patients were divided into three groups depending on their serum phosphorus (<3.5; 3.5-5.5; >5.5 mg/dL). Statistical tests were performed with SPSS, version 20.0. A p < 0.05 was considered significant. On the one hand, hypophosphatemia was significantly associated with better dialysis adequacy, higher age and overhydration. On the other hand, it was associated with lower albumin, protein intake, creatinine, hemoglobin, calcium, potassium, magnesium, body mass index (BMI), body cell mass index, fat tissue index and lean tissue index. These patients had lower survival rates compared with those with normo- and hyperphosphatemia. Hypophosphatemia was a predictor of death when adjusted for age, diabetes, HD vintage, gender, and Kt/V. Comparing the mortality predictors in hypo- and hyperphosphatemia, we found that low albumin, BMI, and high overhydration increased the mortality risk in the hypophosphatemic group, whereas in hyperphosphatemic patients data were not statistically significant. Currently, a high prevalence of hypophosphatemia exists in Portuguese HD patients. This condition is associated with worst nutritional and body composition parameters. In the context of additional indices of malnutrition (low albumin, low BMI or severe overhydration), hypophosphatemic patients presented higher mortality risk.


Blood pressure, the prevalence of cardiovascular diseases, and exposure to cadmium: a population study.
In a population study conducted from 1985 to 1989 in Belgium, the authors investigated whether exposure to cadmium is associated with blood pressure elevation and with an increased prevalence of cardiovascular diseases. The participants, aged 20-88 years, constituted a random sample of the households living in two low exposure areas (n = 803) and two high exposure areas (n = 1,283). For each exposure level, a rural and an urban district were selected. The cadmium levels in blood (8.5 vs. 11.0 nmol/liter) and urine (7.2 vs. 8.7 nmol/24 hours) were significantly (p less than 0.001) raised in the two high exposure areas compared with the two low exposure areas (p less than 0.001). Systolic pressure was similar in both rural areas, but in the urban area with high exposure systolic pressure was 5 mmHg (p less than 0.001) higher than in the control town. Diastolic pressure was similar in the four districts and the same was true for the prevalence of hypertension and of other cardiovascular diseases. Adjustment of systolic pressure for blood and urinary cadmium did not remove the difference in systolic pressure between both urban areas, suggesting that it was not related to the cadmium burden on the environment. Further analyses in individual subjects showed that neither blood pressure nor the presence of cardiovascular diseases were significantly and positively correlated with blood and urinary cadmium. Thus, the present population study did not confirm the hypothesis that increased exposure of the population to cadmium is associated with blood pressure elevation and with a higher prevalence of cardiovascular diseases.


Gender, Escalatory Tendencies, and Verbal Aggression in Intimate Relationships.
This study examined the relationship between gender, escalatory tendencies, and the use of verbal aggression among four types of heterosexual dyads: couples with no verbal aggression, man-only verbal aggression, woman-only verbal aggression, and both-partner verbal aggression. The study was based on a community sample of 65 couples (130 men and women). The findings show that while there is no gender difference in the prevalence and incidence of verbal aggression, there is a difference in the levels of motivation to put one's partner "in his or her place" and avoid a confrontation with one's partner. Thus, there is a gender difference in escalatory tendency. This difference is evident in the greater motivation to put one's partner in his or her place observed among women, as compared with men, and in the lower motivation to avoid confrontation observed among women, as compared with men. Moreover, unlike among men, among women, the motivation to put one's partner in his place is higher than the motivation to avoid confrontation. It follows that the escalatory tendency among women is greater than the escalatory tendency among men. The findings also demonstrate significant gender differences in motivations and escalatory tendencies within the different types of dyads examined. These findings establish the relationship between escalation and aggression and also provide a glimpse into the mechanisms that sustain that relationship.


Comparison of the oral health status and salivary flow rate of asthmatic patients with those of nonasthmatic adults--results of a pilot study.
The oral health status and stimulated salivary flow rate of 33 adult asthmatic outpatients were compared with those of 33 nonasthmatic controls. The groups were matched by age and sex, and an adjustment for education was made in the statistical analysis. In the oral examination, a small difference in the prevalence of caries was observed when the sums of decayed, missing, and filled teeth (DMFT) were compared. The mean (SD) crude DMFT score was 20.1 (5.8) in the asthma group and 18.4 (7.6) in the control group. A statistically significant difference was seen in the amount of periodontal inflammation and in the stimulated salivary flow rate between the groups. The mean (SD) crude periodontal status index (PSI) was 52.7% (23.8%) in the asthmatics and 37.1% (20.4%) in the controls. The 95% confidence interval (95% CI) for the difference in adjusted means of PSI ranged from 0.1% to 21.9% (P = 0.05). In the stimulated salivary flow rate, crude mean values were 1.0 (0.5) ml/min and 1.3 (0.5) ml/min, respectively, and the 95% CI for the difference was from 0.05 ml/min to 0.57 ml/min (P = 0.01). Mucosal lesions in the oral cavity were found in 15 asthmatics (45%) and in eight controls (24%). In conclusion, the results of this study support the hypothesis that adult asthmatics have a higher risk of oral diseases than nonasthmatic subjects.


Tumor-Derived Membrane Vesicles Restrain Migration in Gliomas By Altering Collective Polarization.
Mechanobiology is a cornerstone in physiology. However, its role in biomedical applications remains considerably undermined. In this study, we employed cell membrane vesicles (CMVs), which are currently being used as nanodrug carriers, as tactile cues for mechano-regulation of collective cell behaviors. Gliomas, which are among the most resilient brain tumors and have a low patient survival rate, were used as the cell model. We observed that mechanical responses due to the application of glioma- or microglia-derived CMVs resulted in the doubling of the traction stress of glioma cell collectives with a 10-fold increase in the CMV concentration. Glioma-CMVs constrained cell protrusions and hindered their collective migration, with the migration speed of such cells declining by almost 40% compared to the untreated cells. We speculated that the alteration of collective polarization leads to migration speed changes, and this phenomenon was elucidated using the cellular Potts model. In addition to intracellular force modulation and cytoskeletal reorganization, glioma-CMVs altered drug diffusion within glioma spheroids by downregulating the mechano-signaling protein YAP-1 while also marginally enhancing the associated apoptotic events. Our results suggest that glioma-CMVs can be applied as an adjuvant to current treatment approaches to restrict tumor invasion and enhance the penetration of reagents within tumors. Considering the broad impact of mechano-transduction on cell functions, the regulation of cell mechanics through CMVs can provide a foundation for alternative therapeutic strategies.


The Impact of Systolic Blood Pressure, Pulse Pressure, and Their Variability on Diabetes Retinopathy among Patients with Type 2 Diabetes.
To evaluate the effects of variations in systolic blood pressure (SBP) and pulse pressure (PP) on diabetic retinopathy (DR) in patients with type 2 diabetes. A total of 3275 type 2 diabetes patients without DR at Taiwan Lee's United Clinic from 2002 to 2014 were enrolled in the study. The average age of the patients was 65.5 (±12.2) years, and the follow-up period ranged from 3 to 10 years. Blood pressure variability was defined as the standard deviation (SD) of the average blood pressure values over the entire study period and was calculated for each patient. The mean SD for SBP was 11.16, and a SBP ≥ 130 mmHg (1 mmHg = 0.133 kPa) was defined as high SBP. Based on these data, patients were divided into four groups as follows: group 1 (G1, mean SBP < 130 mmHg, SD of SBP < 11.16 mmHg), group 2 (G2, mean SBP < 130 mmHg, SD ≥ 11.16 mmHg), group 3 (G3, mean SBP ≥ 130 mmHg, SD of SBP < 11.16 mmHg), and group 4 (G4, mean SBP ≥ 130 mmHg, SD ≥ 11.16 mmHg). Based on a mean PP of 80 mmHg with a pulse pressure SD of 6.53 mmHg, the patients were regrouped into four groups designated G1'-G4'. After adjusting for patient age, sex, and disease course, Cox regression showed that the mean and SD of SBP, pulse pressure, and their SDs were risk factors for DR. After stratifying the patients based on the mean and SD of the SBP, we found that the patients in the G4 group had the highest risk of DR (hazard ratio (HR) = 1.980, 95% CI: 1.716~2.285, P < 0.01) and patients in the G1 group had the lowest risk. Patients in the G3 group (HR = 1.409, 95% CI: 1.284~1.546, P < 0.01) had a higher risk of DR compared to those in the G2 group (HR = 1.353, 95% CI: 1.116~1.640, P < 0.01). After the restratification of patients based on the mean and SD of the pulse pressures, it was found that patients in the G2' group had the highest risk of DR (HR = 2.086, 95% CI: 1.641~2.652, P < 0.01), whilst patients in the G1' group had the lowest risk. Also, the risk of DR in the G4' group (HR = 1.507, 95% CI: 1.135~2.000, P < 0.01) was higher than that in the G3' group (HR = 1.289, 95% CI: 1.181~1.408, P < 0.01). Variability in SBP and PP are risk factors for DR in patients with type 2 diabetes. The variability of PP was better able to predict the occurrence of DR than mean pulse pressure.


Polypyrimidine tract-binding protein down-regulates fibroblast growth factor receptor 1 alpha-exon inclusion.
Exclusion of the alpha-exon by alternative RNA splicing of the fibroblast growth factor receptor 1 (FGFR1) primary transcript leads to the production of FGFR1beta. Glial cell transformation is associated with a progressive increase in FGFR1beta expression that coincides with a dramatic increase in the expression of the splicing factor polypyrimidine tract-binding protein (PTB). Cell-specific overexpression of PTB increased alpha-exon skipping, and a reduction in PTB increased alpha-exon inclusion. Targeted disruption of PTB interaction with FGFR1 precursor RNA in vivo by an antisense oligonucleotide also increased alpha-exon inclusion. These results suggest that PTB plays a direct role in alpha-exon splicing.


Tau Positron Emission Tomography Imaging in Degenerative Parkinsonisms.
In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, 18F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.