Pulmonary artery/aorta ratio in simple screening for fetal outflow tract abnormalities during the second trimester.
Congenital heart disease is associated with high mortality and morbidity rates, being the most life-threatening defect in the first month of postnatal life and accounting for approximately half of all childhood mortality from birth defects. Despite this, the prenatal detection rate for congenital outflow tract anomalies by ultrasound imaging is relatively low. The aim of this study was to establish a nomogram for the pulmonary artery/aorta (PA/AO) ratio measured in the three-vessel view plane. This ratio was investigated as a simple screening tool for congenital cardiac outflow tract abnormalities. The study was a prospective evaluation of 966 singleton fetuses at 16-24 weeks of gestation and 46 fetuses with congenital cardiac outflow tract abnormalities. The diameters of the pulmonary artery and aorta were measured in the three-vessel view. The PA/AO ratio was calculated and a nomogram was constructed. The mean and 95% CI for the ratio were defined and the PA/AO ratios of cases with outflow tract abnormalities were plotted against the values for normal fetuses. The gestational age of the normal group ranged from 16 to 24 weeks, with a median of 19 weeks. The pulmonary artery diameter measured between 2.1 and 4.93 mm (mean, 3.3 mm) and the aorta measured between 2.1 and 5.2 mm (mean, 2.93 mm). The mean (SD) PA/AO ratio was 1.16 (0.18) (95% CI, 0.87-1.58; range 0.61-1.86; median, 1.14). For fetuses with outflow tract abnormalities, the median gestation was 19 weeks and 37/43 (86%) had a PA/AO ratio outside the 95% CI. The PA/AO ratio derived from measurements in the three-vessel view plane can be used as an initial screening tool for outflow tract anomalies and may have a sensitivity of up to 86%, with a 5% false-positive rate.


Functions of TopBP1 in preserving genome integrity during mitosis.
TopBP1/Rad4/Dpb11 is an essential eukaryotic protein with important roles in DNA replication, DNA repair, DNA damage checkpoint activation, and chromosome segregation. TopBP1 serves as a scaffold to assemble protein complexes in a phosphorylation-dependent manner via its multiple BRCT-repeats. Recently, it has become clear that TopBP1 is repurposed to scaffold different processes dependent on cell cycle regulated changes in phosphorylation of client proteins. Here we review the functions of human TopBP1 in maintaining genome integrity during mitosis.


Metastasectomy or Stereotactic Body Radiation Therapy With or Without Systemic Therapy for Oligometastatic Esophagogastric Cancer.
The primary goal of this study was to determine overall survival (OS) in patients who underwent local treatment (metastasectomy or stereotactic body radiotherapy [SBRT]) or systemic therapy (chemotherapy or targeted therapy) for oligometastatic esophagogastric cancer. The secondary goal was to determine prognostic factors for OS. Patients with synchronous or metachronous oligometastatic esophagogastric cancer who underwent local treatment or systemic therapy were included in this single-center, retrospective cohort study. Oligometastatic disease (OMD) included 1 organ or 1 extraregional lymph node station with ≤ 3 lesions. OS was determined after OMD detection. Treatment for OMD was categorized as (1) local treatment, (2) local plus systemic, (3) systemic therapy. The primary tumor was controlled after resection or definitive chemoradiotherapy. In total, 85 patients were included. Treatment for OMD was local treatment (58%), local plus systemic (14%), or systemic therapy (28%). The primary tumor was controlled in 68% of patients. Most patients were diagnosed with distal esophageal cancer (61%), with adenocarcinoma histology (76%), and presented with synchronous OMD (51%). OS after local treatment was 17 months (95% confidence interval [CI] 12-40), after local plus systemic therapy 35 months (95% CI 29-NA), and after systemic therapy 16 months (95% CI 11-NA). Better OS was independently associated with local plus systemic compared with local treatment (hazard ratio [HR] 2.11, 95% CI 1.05-5.07) or systemic therapy (HR 2.28, 95% CI 1.04-6.07). Local plus systemic therapy for oligometastatic esophagogastric cancer was independently associated with improved OS and better OS compared with either systemic therapy or local treatment.


Dietary supplementation with synthetic astaxanthin and DHA interactively regulates physiological metabolism to improve the color and odor quality of ovaries in adult female Eriocheir sinensis.
The present study aimed to investigate the interactive effects of dietary supplementation to the feed with astaxanthin and/or DHA on the color and odor of Eriocheir sinensis ovaries. The results revealed that astaxanthin supplementation significantly increased redness of E. sinensis ovaries (P < 0.05). Moreover, the addition of either astaxanthin or DHA alone to the feed affected the deposition of carotenoids and fatty acids in E. sinensis ovaries. More importantly, the simultaneous supplementation of astaxanthin and DHA significantly improved color, carotenoid content, and polyunsaturated fatty acid content (P < 0.05) in E. sinensis ovaries, as well as increased the content of aroma compounds during thermal processing. Based on the present findings, the optimal combination of dietary astaxanthin and DHA is 100 mg/kg of synthetic astaxanthin and 0.15% of DHA, respectively, which could improve color and odor quality of ovaries for E. sinensis.


[MORPHOMETRIC FACTORS OF PROGNOSIS FOR REMOTE RECANALIZATION OF INTRACRANIAL ARTERIAL ANEURYSMS AFTER THEIR ENDOVASCULAR SURGICAL TREATMENT].
The factors of the embolization stability prognostication in remote period after surgical treatment for intracranial arterial aneurysm rupture, were determined. In 34 patients in 6 - 12 mo after embolization of intracranial arterial aneurysms the angiographic control was conducted. In 18 patients (the first group) the signs of a stable embolization were revealed, and in 16 (a second group) - the aneurysm recanalization. The author considers the aneurysms noncorrect (ellipse-like) form, a trustworthy dimensions of the body and volume as a risk factors for recanalization of aneurysms occurence.


Role of telereceptive and interoceptive (taste) cues in ingestional neophobia in chicks (Gallus domesticus).
Experiment 1 investigated the influence of telereceptive (visual) and interoceptive (taste) cues on neophobia by measuring the intakes of clear water and novel solutions of red-colored water, clear 4.0% vinegar, or red-colored 4.0% vinegar in chicks (Gallus domesticus) on 5 test days. Neophobia was reliably greater the more numerous the novel stimuli in testing (i.e., red-colored vinegar) but was similar in magnitude for novel visual and novel taste cues alone. In Experiment 2 chicks received zero, one, or five preexposures to red-colored water or to clear 4.0% vinegar and were tested for neophobia to red-colored 4.0% vinegar. Intake of red vinegar reliably increased with the number of preexposures. However, preexposure to red-colored water facilitated intake of red vinegar more than preexposure to clear 4.0% vinegar did. These results suggest that the familiarity of telereceptive (visual) stimuli attenuates the demonstration of taste neophobia.


Music, pandas, and muggers: on the affective psychology of value.
This research investigated the relationship between the magnitude or scope of a stimulus and its subjective value by contrasting 2 psychological processes that may be used to construct preferences: valuation by feeling and valuation by calculation. The results show that when people rely on feeling, they are sensitive to the presence or absence of a stimulus (i.e., the difference between 0 and some scope) but are largely insensitive to further variations of scope. In contrast, when people rely on calculation, they reveal relatively more constant sensitivity to scope. Thus, value is nearly a step function of scope when feeling predominates and is closer to a linear function when calculation predominates. These findings may allow for a novel interpretation of why most real-world value functions are concave and how the processes responsible for nonlinearity of value may also contribute to nonlinear probability weighting.


Review on recent advances in fabrication of enzymatic and chemical sensors for hypoxanthine.
Hypoxanthine is an important product of the nucleotide degradation pathway. It has been considered as a potential marker for assessing meat freshness and clinical diagnosis. In the review, we focus on advancement made in the fabrication of hypoxanthine sensors. Several traditional methods are being utilized for the detection of hypoxanthine, but these methods are expensive, complex, require pretreatment of the sample which is time-consuming and trained persons to operate. Sensors have emerged as simple, rapid, economic, disposable, and portable tools for hypoxanthine detection in biological samples. In particular, the review describes the significant role of hypoxanthine in clinical and food applications. Classification of sensors into enzymatic and non-enzymatic sensors along with the different methods used for xanthine oxidase immobilization and type of transducers used for hypoxanthine detection are briefly explained.


Cell sorting in a Petri dish controlled by computer vision.
Fluorescence-activated cell sorting (FACS) applying flow cytometry to separate cells on a molecular basis is a widespread method. We demonstrate that both fluorescent and unlabeled live cells in a Petri dish observed with a microscope can be automatically recognized by computer vision and picked up by a computer-controlled micropipette. This method can be routinely applied as a FACS down to the single cell level with a very high selectivity. Sorting resolution, i.e., the minimum distance between two cells from which one could be selectively removed was 50-70 micrometers. Survival rate with a low number of 3T3 mouse fibroblasts and NE-4C neuroectodermal mouse stem cells was 66 ± 12% and 88 ± 16%, respectively. Purity of sorted cultures and rate of survival using NE-4C/NE-GFP-4C co-cultures were 95 ± 2% and 62 ± 7%, respectively. Hydrodynamic simulations confirmed the experimental sorting efficiency and a cell damage risk similar to that of normal FACS.


LVPEI Glaucoma Epidemiology and Molecular Genetic Study: teleophthalmology screening for angle-closure disease in an underserved region.
To assess the ability of teleophthalmoscopic grading of peripheral anterior chamber depth (PACD) using the van Herick (vH) technique in detecting gonioscopically occludable angle; and to determine whether combining results from vH grading and ocular biometry can improve the accuracy to diagnose gonioscopically occludable angle METHODS: This cross-sectional study was an offshoot of a rural population-based study, Glaucoma Epidemiology and Molecular Genetic Study (GLEAMS). A masked urban ophthalmologist graded digital slit lamp photographs of PACD by vH technique. Sussman four-mirror lens was used to perform dark room indentation gonioscopy. Cutoff values of the tests were, vH technique: grade ≤ 2, central anterior chamber depth (ACD), as well as axial length: ≤ 25th percentile and lens thickness ≥ 75th percentile value of the study population. We studied 1965 eyes of 1029 adult participants. The vH grade was ≤2 in 188 (9.5%) eyes. The angle was occludable by gonioscopy in 101 (5.1%) eyes. The performance of the vH test to rule out gonioscopically occludable angle was good [negative predictive value (NPV): 97.3%], despite low sensitivity (52.5%), while its efficacy to rule in the condition was low [positive predictive value (PPV): 28.2%] despite high specificity (92.8%). However, test combination strategy increased the PPV nearly twofold (53.8%). The calculated PPV at 10% prevalence of gonioscopically occludable angle was even higher (70.5%). Van Herick technique can be incorporated into a teleophthalmology program by means of slit lamp photographs of PACD. Combined vH grading and ocular biometry improved the predictability of a gonioscopically occludable angle.


Hidden and apparent twins in uranyl-oxide minerals agrinierite and rameauite: a demonstration of metric and reticular merohedry.
In this work, the structures of chemically related uranyl-oxide minerals agrinierite and rameauite have been revisited and some corrections to the available structure data are provided. Both structures were found to be twinned. The two minerals are chemically similar, and though their structures differ considerably, their unit-cell metrics are similar. Agrinierite was found to be twinned by metric merohedry (diffraction type I), whereas the structure of rameauite is twinned by reticular merohedry (diffraction type II). The twinning of the monoclinic unit cells (true cells) leads to pseudo-orthorhombic or pseudo-tetragonal supercells in the single-crystal diffraction patterns of both minerals. According to the new data and refinement, agrinierite is monoclinic (space group Cm), with a = 14.069 (3), b = 14.220 (3), c = 13.967 (3) Å, β = 120.24 (12)° and V = 2414.2 (12) Å3 (Z = 2). The twinning can be expressed as a mirror in (101) (apart from the inversion twin), which leads to a supercell with a = 14.121, b = 14.276, c = 24.221 Å and V = 2 × 2441 Å3, which is F centered. The new structure refinement converged to R = 3.54% for 6545 unique observed reflections with I > 3σ(I) and GOF = 1.07. Rameauite is also monoclinic (space group Cc), with a = 13.947 (3), b = 14.300 (3), c = 13.888 (3) Å, β = 118.50 (3)° and V = 2434.3 (11) Å3 (Z = 2). The twinning can be expressed as a mirror in (101) (apart from the inversion twin), which leads to a supercell with a = 14.223, b = 14.300, c = 23.921 Å and V = 2 × 2434 Å3, which is C centered. The new structure refinement of rameauite converged to R = 4.23% for 2344 unique observed reflections with I > 3σ(I) and GOF = 1.48. The current investigation documented how peculiar twinning can be, not only for this group of minerals, and how care must be taken in handling the data biased by twinning.


[Systemic inflammation, "sickness behavior" and expectations : What role do expectations play in inflammation-associated symptoms?]
Systemic inflammation is accompanied by unspecific physical and psychological symptoms of sickness, including pain and affective symptoms. These symptoms (commonly called "sickness behavior") are mediated by the central nervous effects of immune messengers such as pro-inflammatory cytokines. While adaptive during acute inflammation, sickness symptoms can have detrimental effects on quality of life during chronic inflammation and may contribute to comorbidity in chronic pain conditions. Despite the high clinical relevance of sickness behavior, psychological interventions aiming to modulate sickness symptoms have hardly been investigated. One approach could be the use of expectation effects, since positive and negative expectations (placebo or nocebo effects) have been shown to have an influence on pain and affect-related symptoms. Herein, we summarize immunological and psychobiological factors that contribute to pain in the context of sickness behavior, with a major focus on findings from experimental endotoxemia. Against this background, we discuss how expectations could help to improve immune-mediated sickness symptoms and outline potential psychological and psychobiological mechanisms underlying this putative effect.


Exploring the concerns of second-degree dental students on entering specialist OMFS training and their attitudes towards the second-degree curriculum.
Within the UK, oral and maxillofacial surgery (OMFS) is a competitive specialty with a rigorous training programme that currently requires dual degrees in both medicine and dentistry. Training in OMFS can present various challenges in terms of finances, length of training, and work-life balance. The current study explores the concerns of second-degree dental students in trying to obtain an OMFS specialty training post, as well as their views on the second-degree curriculum. An online survey was distributed via social media to second-degree dental students across the UK and 51 responses were received. Respondents cited a lack of publications (29%), specialty interviews (29%), and the OMFS logbook (29%) as the primary concerns about securing a higher training post. Eighty-eight per cent felt there were elements of repetition within the second degree for which competencies had already been achieved, and 88% agreed with streamlining the curriculum within the second degree. We propose that the second degree should incorporate ways to build the OMFS ST1/ST3 portfolio as part of a tailored curriculum, removing or condensing the repetitive elements, and instead emphasising areas of concern for trainees such as research, operative experience, and interview guidance. Second-degree students should be provided with mentors with an interest in research and academia to provide guidance and promote early interest in academia.


Primary leiomyosarcoma of the diaphragm.
Primary leiomyosarcoma of the diaphragm is extremely rare and only five cases have so far been reported. In the early stages clinical signs are scarce and diagnosis is difficult. The advent of MR-imaging has helped in detecting the origin of a diaphragmatic tumour and its relationship to the adjacent tissues. The highly malignant character of this tumour accounts for the poor prognosis even when radical surgery is performed.


Ultrasonographic Assessment of Glenohumeral Joint Stability Immediately After Arthroscopic Bankart-Bristow Procedure.
The changes in glenohumeral joint stability after surgery in a clinical setting are yet unknown. This study aimed to compare the anterior humeral head translation between pre- and postsurgical conditions using ultrasonography. It was hypothesized that ultrasonographic assessment would reveal decreased anterior translation. Case series; Level of evidence, 4. A total of 27 patients (24 male, 3 female; mean age, 24.1 ± 9.7 years) with anterior shoulder instability were studied prospectively. All the patients underwent the arthroscopic Bankart-Bristow procedure under general anesthesia, and ultrasonographic evaluation was performed before and immediately after surgery. The forearm was fixed with an arm positioner in the beach-chair position, and the ultrasonographic transducer was located at the posterior part of the shoulder to visualize the humeral head and glenoid rim at the level of interval between the infraspinatus tendon and teres minor tendon. The upper arm was drawn anteriorly with a 40-N force at 0°, 45°, and 90° of shoulder abduction with neutral rotation. The distance from the posterior edge of the glenoid to that of the humeral head was measured using ultrasonography with and without anterior force. Anterior translation was defined by subtracting the distance with anterior force from the distance without anterior force. The humeral head position was translated posteriorly immediately after surgery in all patients. Anterior translation decreased significantly after surgery at 45° (7.7 ± 4.3 vs 5.8 ± 2.0 mm; P = .031) and 90° (8.9 ± 3.4 vs 6.1 ± 2.2 mm; P < .001) of abduction, whereas there was no difference between pre- and postsurgical translation at 0° of abduction (4.9 ± 2.3 vs 4.0 ± 2.1 mm, P = .089). Ultrasonographic assessment immediately after a Bankart-Bristow procedure showed the humeral head was translated posteriorly relative to the glenoid at 0°, 45°, and 90° of abduction. The surgery also decreased anterior translation in response to an anteriorly directed force at 45° and 90° of abduction.


Microgroove cushion of robotic endoscope for active locomotion in the gastrointestinal tract.
The robotic endoscope the advantage of active locomotion in the gastrointestinal (GI) tract, but lacks a suitable contact device to improve the locomotion efficiency and safety. This paper proposes a microgroove cushion for the robotic endoscope to improve its active locomotion ability in the GI tract. Coupons with different microgrooves were designed and tested to verify the contact efficiency of the grooves. Based on experimental investigations, uniform oblique grid grooves were suggested, because they could generate gteater friction than other proposed microgrooves on the intestinal surface. To improve the contact safety of the robotic endoscope, a cushion-type contact device was designed and fabricated. The microgroove cushion was tested under the use of a custom-built robot. An experiment in a rigid tube showed that the robot with cushion had a static friction 65% higher than the robot without cushion; an experiment in the in vitro colonic tract showed that the robot without the cushion produced a more obvious contact appearance than with the cushion. It can be seen that the microgroove cushion provides the robotic endoscope with efficient and safe contact ability. The microgroove cushion is a useful addition to the development of a contact device for the robotic endoscope in the GI tract, although requiring further improvements.


Investigation into experiences of older students undertaking a Pre-registration Diploma in Nursing.
This paper sets out to investigate the experiences of older students undertaking a Pre-registration Diploma in Nursing in a large college of nursing in Belfast. Questionnaires were sent to all students aged 21 years or over on starting the course since its inception in February 1991. These amounted to 92 students. Quantitative and qualitative data were collected regarding the problems, needs and issues surrounding older students. The findings indicate that the college is not adequately meeting the needs of many older students and this is also the case when students are in the clinical area. Most of the respondents already had a high level of education and work experience. However, most were disappointed by the fact that this experience and their maturity was not always recognized, particularly in the clinical setting. This study provides clear evidence to suggest that older students perceive themselves to be more motivated than younger students and better able to study independently. However, even though older students may have some advantages over younger students they do have specific problems and needs which should be addressed. These are related to various issues amongst which may be finance, family commitments, academic study, difficulties in their adaptability and the speed at which they are able to learn new skills.


Interplay between external inputs and recurrent dynamics during movement preparation and execution in a network model of motor cortex.
The primary motor cortex has been shown to coordinate movement preparation and execution through computations in approximately orthogonal subspaces. The underlying network mechanisms, and the roles played by external and recurrent connectivity, are central open questions that need to be answered to understand the neural substrates of motor control. We develop a recurrent neural network model that recapitulates the temporal evolution of neuronal activity recorded from the primary motor cortex of a macaque monkey during an instructed delayed-reach task. In particular, it reproduces the observed dynamic patterns of covariation between neural activity and the direction of motion. We explore the hypothesis that the observed dynamics emerges from a synaptic connectivity structure that depends on the preferred directions of neurons in both preparatory and movement-related epochs, and we constrain the strength of both synaptic connectivity and external input parameters from data. While the model can reproduce neural activity for multiple combinations of the feedforward and recurrent connections, the solution that requires minimum external inputs is one where the observed patterns of covariance are shaped by external inputs during movement preparation, while they are dominated by strong direction-specific recurrent connectivity during movement execution. Our model also demonstrates that the way in which single-neuron tuning properties change over time can explain the level of orthogonality of preparatory and movement-related subspaces.


Phase I trial of neoadjuvant chemoradiation with gemcitabine and surgical resection for cholangiocarcinoma patients (NACRAC study).
The feasibility of neoadjuvant chemoradiation therapy for cholangiocarcinoma, followed by conventional resection, has not been determined yet. Here, a phase I study of neoadjuvant chemoradiation therapy, named NACRAC, was performed to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of gemcitabine when combined with external beam radiation therapy for resectable cholangiocarcinoma. From August 2007 to June 2008, 12 patients provided informed consent. Preoperative radiation was administered in 1.8Gy daily fractions up to a total dose of 45Gy. Gemcitabine was administered at day 1 and 8 every three weeks. The initial dose of gemcitabine was started from 400mg/m2. One patient was not able to start treatment because of bleeding caused by a duodenal ulcer and cholangitis. At 800mg/m2 of gemcitabine, one patient out of three failed to complete the treatment because of Grade 3 hematological toxicity. In another three cases of 800mg/m2, the second case could not complete the treatment because of cholangitis. Then, 600mg/m2 was determined to be the MTD, and the RD dose decided as 600mg/m2. The RD of gemcitabine in NACRAC study was determined to be 600mg/m2. NACRAC study should proceed to a phase II trial to evaluate the effectiveness.


Rules of tumor cell development and their application to biomarkers for ovarian cancer.
To apply the Hanahan and Weinberg conceptual framework for tumor development to the specific biomarkers observed or expressed in ovarian cancer. Data-based publications, topical reviews, and book chapters. Articles specific to ovarian cancer were reviewed to examine whether the six rules from the Hanahan and Weinberg conceptual framework were applicable to biomarkers of ovarian cancer. This approach allows for the application of a general framework for the development of solid tumors to the development of ovarian cancer. The six rules for tumor cell development outlined in the Hanahan and Weinberg conceptual framework are applicable to biomarkers expressed or observed in patients with ovarian cancer. Oncology nurses can enhance their clinical teaching by integrating this information into their practice. Nurses who conduct research on ovarian cancer can use this framework to guide the selection of biomarker(s) for these studies. Finally, nurse educators can use this framework when teaching students key concepts in the care of patients with cancer.


Expression analysis of matrix metalloproteinase-9 in epithelialized and nonepithelialized apical periodontitis lesions.
The objective of this study was to determine the expression of matrix metalloproteinase-9 (MMP-9) in apical periodontitis lesions. Nineteen epithelialized and 18 nonepithelialized apical periodontitis lesions were collected after periapical surgery. After histological processing, serial sectioning, H&E staining, and microscopic analysis, 10 epithelialized and 10 nonepithelialized lesions were selected for immunohistochemical analysis for MMP-9 and CD 68. At least one third of each specimen collected was frozen at -70 degrees C for further mRNA isolation and reverse transcription into cDNA for real-time-PCR procedures. Geometric averaging of multiple housekeeping genes normalized MMP-9 mRNA expression level. Polymorphonuclear neutrophils, macrophages and lymphocytes presented MMP-9 positive immunostaining in both types of lesions. When present, epithelial cells were also stained. The number and the ratio of MMP-9(+)/total cells were greater in nonepithelialized than epithelialized lesions (P = .0001) presenting a positive correlation to CD68(+)/total cells (P = .045). Both types of lesions presented increased MMP-9 expression (P < .0001) when compared to healthy periapical ligaments. However, no significant differences were observed for MMP-9 mRNA expression between ephithelized and nonephithelized lesions. The present data suggest the participation of several inflammatory cells, mainly CD68(+) cells, in the MMP-9 expression in apical periodontitis lesions. MMP-9 could be actively enrolled in the extracellular matrix degradation in apical periodontitis lesions.


Recent advances in familial amyloid polyneuropathy.
To highlight the advances in the knowledge of the clinical features, diagnostic techniques, clinimetrics, and therapeutics of transthyretin familial amyloid polyneuropathy. Expanding knowledge of the molecular underpinnings and therapeutics of transthyretin familial amyloid polyneuropathy have provided impetus to molecular-specific phenotype characterization, natural history studies, and target-based therapeutic interventions. These interventions have underscored the need for early, accurate diagnostic instruments and sensitive diagnostic and therapeutic biomarkers. Current and emerging target-based therapeutic interventions and novel diagnostic techniques may contribute to improved quality of life and survival in this disease.


Left ventricular outflow tract closure during LVAD implantation: 2 cases of patients supported for over 6 years.
We previously reported a series of 5 patients with advanced heart failure and aortic insufficiency (AI) who underwent concomitant left ventricular outflow tract (LVOT) closure at the time of continuous-flow left ventricular assist device (CF-LVAD) implantation. Although this technique of treating AI has been shown to be effective in the short term, its long-term durability has not been well studied. Here, we report the long-term outcomes of two patients with severe AI who underwent LVOT closure at the time of CF-LVAD implantation. Each of the two patients survived for more than 6 years without any complications related to LVOT closure.


Modality pairing effects and the response selection bottleneck.
The present experiment examined the effects of input/output modality pairings on dual-task performance using the psychological refractory period (PRP) procedure. Four groups of participants performed two tasks composed of the same sets of inputs (visual and auditory) and the same sets of outputs (manual and vocal), but with different input/output modality pairings. Whereas modality pairings had only small effects on single-task reaction times, they had large effects on dual-task reaction times. The modality pairing effect cannot stem from differences in the difficulty of stimulus classification or response execution, because these task demands were the same across groups. The effect also does not appear to result from changes in stimulus-response compatibility. The present findings suggest dual-task interference arises not only from postponement of central operations (due to a central bottleneck), but also from a slowing of central operations whose magnitude is sensitive to the input/output modality pairings.


The effectiveness of physiotherapy in patients with asthma: a systematic review of the literature.
Since the introduction of medical therapy for asthma the interest in non-medical treatments deteriorated. Physiotherapy could have beneficial effects in asthmatics. This review investigates the effectiveness of physiotherapy in the treatment of patients with asthma. A review was performed on the terms breathing exercises (BE), inspiratory muscle training (IMT), physical training (PhT) and airway clearance (AC) in patients with asthma. The search resulted in 237 potentially relevant articles, after exclusion 23 articles remained. BE (n = 9) may improve disease specific quality of life (QoL), reduce symptoms, hyperventilation, anxiety and depression, lower respiratory rate and medication use. IMT (n = 3) can improve inspiratory pressure and may reduce medication use and symptoms. PhT (n = 12) can reduce symptoms, improve QoL and improve cardiopulmonary endurance and fitness. In conclusion, physiotherapy may improve QoL, cardiopulmonary fitness and inspiratory pressure and reduce symptoms and medication use. Further studies, investigating combinations of techniques, are needed to confirm these findings.


Structural model of factors contributing to the motivational problem of taking shortcuts at construction workplaces in the Kingdom of Saudi Arabia.
An unsafe act is a type of work that involves some risk. Since more than a decade, unsafe act has accounted as a foremost cause of work-related accident, especially in the field of construction. Several attempts have been made to reduce the causes of unsafe acts; however, shortcut, which is a notable type of unsafe act, has received little attention in previous works, even though some of causal effects have been attributed to this habit. This paper aims to reveal an unexplained proportion that can be explained by different underlying causes of motivational problems to shortcuts rather than by habit. Accordingly, two structural models have been proposed based on quantitative and qualitative data from previous reviews associated with the effects on negative feeling and thinking on risk management. These models were tested using on Exploratory Factor analysis (EFA) and Confirmatory Factor Analysis (CFA) on data collected from a cross-section survey conducted at construction sites in largest cities within the Kingdom of Saudi Arabia (KSA), where large number of accidents in these cities occurred. Data of 204 respondents of the mailed questionnaires were analyzed after screening all responses. Statistical Package for Social Sciences (SPSS) (version 22) was used to test for Structural Equation Model (SEM) assumptions. The developed hypotheses were tested and model with the best fit was identified. Findings revealed that 45%-55% of the motivational problems to shortcuts were explained by the selected structural model.


Effect of temperature on performance and microbial diversity in hyperthermophilic digester system fed with kitchen garbage.
The objective of this study was to evaluate the performances and microbial diversities for development of the effective hyperthermophilic digester system that consists of hyperthermophilic reactor and hyperthermophilic or thermophilic reactor in series. Lab-scale reactors were operated continuously fed with artificial kitchen garbage. The effect of temperature on the acidification step was firstly investigated. Results indicated that 43.1% of COD solubilization was achieved at 70 degrees C, while it was about 21% at 80 degrees C. The average protein solubilization reached to 31% at 80 degrees C. Methane conversion efficiency following the acidification was around 85% in average at 55 degrees C, but decreased with increasing temperature and methane gas was not produced over 73 degrees C. The upper temperature limits for growth of microbes were secondly observed and shown to be 73 degrees C for acetate oxidizers, 65 degrees C for propionate oxidizers, 70 degrees C for iso-butyrate oxidizers, 80 degrees C for lactate oxidizers and 65 degrees C for protein degrading bacteria in the methane fermenter. As well as, microbes affiliated with methanogens dominated the population below the 65 degrees C, while those affiliated with acidogens were predominant over the 73 degrees C. These results indicated that the hyperthermophilic processes have considerable benefits to treat wastewater or waste containing high concentration of protein.


Glycemic Index, Glycemic Load, and Lung Cancer Risk in Non-Hispanic Whites.
Postprandial glucose (PPG) and insulin responses play a role in carcinogenesis. We evaluated the association between dietary glycemic index (GI) and glycemic load (GL), markers of carbohydrate intake and PPG, and lung cancer risk in non-Hispanic whites. GL and GI were assessed among 1,905 newly diagnosed lung cancer cases recruited from the University of Texas MD Anderson Cancer Center (Houston, TX) and 2,413 healthy controls recruited at Kelsey-Seybold Clinics (Houston, TX). We assessed associations between quintiles of GI/GL and lung cancer risk and effect modification by various risk factors. ORs and 95% confidence intervals (CI) were estimated using multivariable logistic regression. We observed a significant association between GI [5th vs. 1st quintile (Q) OR = 1.49; 95% CI, 1.21-1.83; P(trend) <0.001] and lung cancer risk and GI(ac) (5th vs. 1st Q OR = 1.48; 95% CI, 1.20-1.81; P(trend) = 0.001) and lung cancer risk. We observed a more pronounced association between GI and lung cancer risk among never smokers (5th vs. 1st Q OR = 2.25; 95% CI, 1.42-3.57), squamous cell carcinomas (SCC; 5th vs. 1st Q OR = 1.92; 95% CI, 1.30-2.83), and those with less than 12 years of education (5th vs. 1st Q OR = 1.75; 95% CI, 1.19-2.58, P(interaction) = 0.02). This study suggests that dietary GI and other lung cancer risk factors may jointly and independently influence lung cancer etiology. Understanding the role of GI in lung cancer could inform prevention strategies and elucidate biologic pathways related to lung cancer risk.


Thermal treatment and infectivity of hepatitis A virus in human feces.
The susceptibility of white-lipped marmoset monkeys (Saguinus sp) to human hepatitis A virus (HAV) provides a system for evaluation of thermal inactivation of HAV in feces and contaminated shellfish. Intramuscular or oral administration of HAV derived from feces of four patients with acute hepatitis A induced hepatitis in 28--100% of the inoculated marmosets. A 10% (w/v) fecal pool (GBG-BM) prepared from two patients (GBG and GBM) induced hepatitis in marmosets (2/4 with 1 ml; 2/2 with 3 ml) when given orally as a 1 : 3 dilution. A HAV-baby food raw oyster mixture fed to fasted marmosets induced hepatitis in 1/4 and seroconversion in 2/4 animals. Two groups of oysters were injected with HAV (concentrated 3 : 1 by centrifugation of the GBG-BM pool); one group was treated at 140 degrees F for 19 minutes and the other served as an untreated control. In animals fed the untreated inoculum, 4/6 developed hepatitis and 6/6 seroconverted, whereas of those fed the heat-treated inoculum 1/7 developed hepatitis and 2/7 seroconverted. These data suggest that pasteurization methods could be developed that would eliminate shellfish-associated hepatitis A and retain the palatability of the shellfish.


Dental care among young adults with intellectual disability.
Dental care among young adults with intellectual disability (ID) is poorly documented and largely unmet. By using population-based data from the Metropolitan Atlanta Developmental Disabilities Follow-Up Study, we assessed factors associated with at least one or two dental visits per year among young adults with and without ID. Significantly fewer young adults with ID (45%) visited a dentist at least once per year, compared with those without ID (58%). ID severity and the presence of co-occurring developmental disabilities predicted dental care use. Sociodemographics, daily functioning, societal participation, dental services, and dental health factors were examined as predictors of dental care frequency. Our findings can help focus efforts toward improving the frequency of dental care visits among young adults with ID.


Gut Microbiota Modifications and Weight Regain in Morbidly Obese Women After Roux-en-Y Gastric Bypass.
The relationship between late post-bariatric surgery weight regain and gut microbiota is not completely understood. To analyze the profile of gut microbiota among patients with and without late weight regain after post-Roux-en-Y gastric bypass (RYGB) and to compare it with a control group (CG) comprised of obese Brazilian individuals. This is a cross-sectional study which enrolled 34 morbidly obese women divided into 3 groups: post-Roux-en-Y gastric bypass without (RYGB_non-regain), and with weight regain (RYGB_regain) at least 5 years after surgery, and a CG of preoperative individuals. Gut microbiota was determined by metagenomic analyses. The alpha diversity was higher in groups RYGB non-regain and RYGB regain when compared with CG (p < 0.05). Both RYGB non-regain and RYGB regain groups showed a lower abundance of the phylum Bacteroidetes when compared with CG (p < 0.01). The genera Bacteroides and SMB53 were increased in CG (p < 0.05). Group RYGB non-regain showed more abundance of the Akkermansia genus when compared with CG and group RYGB regain (p < 0.05). RYGB non-regain showed a greater abundance of the Phascolarctobacterium genus and lower of the SMB53 genus when compared with CG (p < 0.05). RYGB non-regain showed a greater abundance of the Phascolarctobacterium genus and a lower of the SMB53 genus when compared with CG (p < 0.05). The gut microbiota of individuals which presented late weight regain after RYGB was significantly different in comparison to individuals with a successful weight loss, a finding that points towards a significant role of gut microbiota on weight loss and maintenance after surgery.


Social isolation and loneliness as related to progression and reversion of frailty in the Survey of Health Aging Retirement in Europe (SHARE).
Frailty was shown to be associated with psychosocial risk factors, but there are few longitudinal data. We used data from waves 5 and 6 of the Survey of Health Aging Retirement in Europe (SHARE) to study the contribution of loneliness and social isolation to transitions towards frailty defined according to Fried criteria in a sample of 27,468 individuals aged ≥60. At baseline, there were 13,069 (47.6%) robust individuals, 11,430 (41.6%) pre-frail and 2,969 (10.8%) frail. After 2 years, among robust subjects at baseline, 8,706 (61.8%) were still robust, 4,033 (30.8%) were pre-frail and 330 (2.6%) were frail. Among those who were pre-frail, 1,504 (13.2%) progressed to frail and 3,557 (31.1%) became robust. Among frail people, 182 (6.1%) reversed to robust and 1,271 (42.8%) to pre-frail. Average and high levels of loneliness and social isolation were significantly associated with the risk of robust people becoming frail and pre-frail (except robust with high loneliness to become frail), and of pre-frail people to become frail (except with average loneliness). Reversion to robustness was inversely associated with high levels of loneliness. Average levels of loneliness and social isolation should not be considered acceptable and should be actively addressed even in the absence of any health conditions through an available evidence-based intervention.


Collision avoidance analysis of human-robot physical interaction based on null-space impedance control of a dynamic reference arm plane.
When the terminal upper limb rehabilitation robot is used for motion-assisted training, collisions between the manipulator links and the human upper limb may occur due to the null-space self-motion of the redundant manipulator. A null-space impedance control method based on a dynamic reference arm plane is proposed to realize collision avoidance during human-robot physical interaction motion for the collision problem between the manipulator links and the human upper limb. Firstly, a dynamic model and a Cartesian impedance controller of the manipulator are established. Then, the null-space impedance controller of the redundant manipulator is established based on the dynamic reference plane, which manages the null-space self-motion of the redundant manipulator to prevent collision between the manipulator links and the human upper limb. Finally, it is experimentally verified that the method proposed in this paper can effectively manage the null-space self-motion of the redundant manipulator, and thus achieve collision avoidance during the human-robot physical interaction motion. This research has significant potential in improving the safety and feasibility of motion-assisted training with rehabilitation robots.


[Profilometric evaluation in orthodontico-surgical treatment planning].
The Authors propose the use of three profilometric analysis to obtain a total aesthetic evaluation of facial proportion and balance. Each analysis is commented explaining specific advantages in orthodontic-surgical treatment planning.


Communication between the Anterior Cingulate Cortex and Ventral Tegmental Area during a Cost-Benefit Reversal Task.
The anterior cingulate cortex (ACC) is implicated in value-based decision making, anticipation, and adaptation; however, how ACC activity modulates these behaviors is unclear. One possibility is via the ACC's connections with the ventral tegmental area (VTA), a dopaminergic region implicated in motivation and feedback processing. We tested this by monitoring ACC and VTA local field potentials in rats performing a cost-benefit reversal task that elicited both value-based and anticipatory choices. Partial directed coherence analyses revealed that elevated 4-Hz ACC-to-VTA signaling accompanied decisions that appeared to be anticipatory. ACC-to-VTA signaling also occurred post-reversal, consistent with it being involved in the initiation of non-default behavior. An analysis of 4-Hz signals in the other direction (VTA-to-ACC) revealed that it was elevated when the rats committed errors and that this signal was followed by behavioral adaptation. Together, these findings suggest that bidirectional communication between the ACC and VTA supports behavioral flexibility.


Genes with spiralian-specific protein motifs are expressed in spiralian ciliary bands.
Spiralia is a large, ancient and diverse clade of animals, with a conserved early developmental program but diverse larval and adult morphologies. One trait shared by many spiralians is the presence of ciliary bands used for locomotion and feeding. To learn more about spiralian-specific traits we have examined the expression of 20 genes with protein motifs that are strongly conserved within the Spiralia, but not detectable outside of it. Here, we show that two of these are specifically expressed in the main ciliary band of the mollusc Tritia (also known as Ilyanassa). Their expression patterns in representative species from five more spiralian phyla-the annelids, nemerteans, phoronids, brachiopods and rotifers-show that at least one of these, lophotrochin, has a conserved and specific role in particular ciliated structures, most consistently in ciliary bands. These results highlight the potential importance of lineage-specific genes or protein motifs for understanding traits shared across ancient lineages.


Deletion of LTbetaR augments male susceptibility to Plasmodium chabaudi.
SUMMARY Disruption of the lymphotoxin beta receptor (LTbetaR) gene has been shown to result in enhanced resistance of female mice to blood-stage Plasmodium chabaudi malaria. Here, we investigate the effect of LTbetaR deletion on host defence of males. In contrast to females, male LTbetaR(-/-) mice do not exhibit any increase in resistance. Conversely, they are even more susceptible than wild-type C57BL/6 mice, which becomes evident after lowering circulating levels of testosterone by castration, which makes C57BL/6 males resistant, whereas LTbetaR(-/-) remain susceptible. Gene-expression analysis using cDNA arrays revealed no differences in immunological responses in spleen of malaria-resistant female and malaria-susceptible castrated male LTbetaR(-/-) mice. In the liver, however, expression levels of plasminogen activator inhibitor PAI1, chemokine CXCL10, dual specificity phosphatase DUSP1, and hydroxysteroid-specific sulfotransferases Sult2a1/2 were decreased 6- to 85-fold in susceptible castrated male LTbetaR(-/-) mice in comparison to resistant female LTbetaR(-/-) mice at maximal parasitaemia, as evidenced by Northern blot analyses. The present data support our previous view that the liver is involved in the combat against malarial blood stages and that down-regulation of the genes DUSP1 and Sult2a1/2 signals dysregulation of protective liver responses, thus possibly contributing to male susceptibility of LTbetaR(-/-) mice.


The fat and thin of lipin.
Mutations in the Lpin1 gene (encoding lipin) cause the lipodystrophy (adipose tissue deficiency) of the fld mouse, but the underlying mechanism has been unclear. In this issue of Cell Metabolism, Phan and Reue (2005) show that overexpression of lipin in either muscle or adipose tissue increases adiposity. Interestingly, mice overexpressing lipin in muscle are insulin resistant, while those overexpressing lipin in adipose tissue are insulin sensitive.


[Radiation-induced sexual toxicity].
Oncosexuality has recently become a new supportive care mission. Sexual morbidity is, routinely, underestimated and must be questioned. We report here the most frequent disorders for men and for women, how to prevent them and how to treat them.


Effects of DM-9384, a pyrrolidone derivative, on alcohol- and chlordiazepoxide-induced amnesia in mice.
The effects of N-(2,6-dimethyl-phenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide (DM-9384), a new pyrrolidone derivative, were investigated on ethanol- and chlordiazepoxide (CDP)-induced amnesia animal model using the passive avoidance task in comparison with aniracetam, another pyrrolidone derivative. Pretraining administration of DM-9384 attenuated ethanol- and CDP-induced amnesia, whereas aniracetam failed to do so. The effects of DM-9384 on CDP-induced amnesia were antagonized by bicuculline, a GABAA receptor antagonist, but not by scopolamine, a muscarinic acetylcholine receptor antagonist and flumazenil, a benzodiazepine receptor antagonist. These results suggest that DM-9384 attenuates CDP-induced amnesia by interacting with the GABAergic neuronal system.


The kinetics of platelet and fibrin deposition on to damaged rabbit carotid arteries in vivo: involvement of platelets in the initial deposition of fibrin.
Thrombus formation in the rabbit carotid artery has been studied kinetically in vivo using a minimally invasive technique utilising radioisotopes. Clamping of the carotid artery for 5 min resulted in the simultaneous accumulation of platelets and fibrin at the site of injury over the next 45 min. Under the electron microscope the response was seen to range from platelet monolayer adhesion to mural thrombus formation with fibrin deposition. In animals rendered thrombocytopenic, fibrin deposition was impaired during the first 15-20 minutes after injury. Basic coagulation times and fibrinogen concentration were within normal limits. In addition the injured vessels in these animals accumulated more radiolabelled albumin, but not erythrocytes, than injured vessels in control animals. The results may imply a role for platelets in the enhancement of fibrin deposition during the early part of the response to injury and in contributing to the maintenance of normal permeability following vessel injury.


Dorsolateral prefrontal and superior temporal volume deficits in first-episode psychoses that evolve into schizophrenia.
Regions with a likely involvement in schizophrenia may differ between patients with first-episodes of psychosis respectively with and without evolution into schizophrenia following the initial episode. We have used magnetic resonance imaging (MRI) to assess the volumes of dorsolateral prefrontal (DLPF) and superior temporal gyrus (STG) in a group of 37 first-episode psychotic patients. After an initial MRI study performed by the time of the first episode, the subjects were followed for two years. After this period 22 cases were diagnosed with schizophrenia, while the other 15 did not show clinical evidence for this illness. A Talairach-based tool was used for segmentation and volumetry of the MRI scans. A group of 44 healthy controls was used for comparison and, using lineal regression, to control for the normal effects of age and intracranial volume on the regional parameters of the patients. By the time of their first episode, patients with schizophrenia had significantly less grey matter in the right DLPF and STG regions as compared to both controls and FE without schizophrenia. Nevertheless, these parameters could not predict final diagnosis in a discriminant analysis model. Our findings indicate that subtle structural defects are already found by the time of the first psychotic break in schizophrenia, although clinical implications for these differences seem unclear.


Colombian Consensus on the Treatment of Placenta Accreta Spectrum (PAS)
Placenta accreta spectrum (PAS) is a condition associated with massive postpartum bleeding and maternal mortality. Management guidelines published in high income countries recommend the participation of interdisciplinary teams in hospitals with sufficient resources for performing complex procedures. However, some of the recommendations contained in those guidelines are difficult to implement in low and medium income countries. The aim of this consensus is to draft general recommendations for the treatment of PAS in Colombia. Twenty-three panelists took part in the consensus with their answers to 31 questions related to the treatment of PAS. The panelists were selected based on participation in two surveys designed to determine the resolution capabilities of national and regional hospitals. The modified Delphi methodology was used, introducing two successive discussion rounds. The opinions of the participants, with a consensus of more than 80%, as well as implementation barriers and facilitators, were taken into consideration in order to issue the recommendations. The consensus draftedfive recommendations, integrating the answers of the panelists. Recommendation 1. Primary care institutions must undertake active search of PAS in patients with risk factors: placenta praevia and history of myomectomy or previous cesarean section. In case of ultrasound signs suggesting PAS, patients must be immediately referred, without a minimum gestational age, to hospitals recognized as referral centers. Online communication and care modalities may facilitate the interaction between primary care institutions and referral centers for PAS. The risks and benefits of telemedicine modalities must be weighed. Recommendation 2. Referral hospitals for PAS need to be defined in each region of Colombia, ensuring coverage throughout the national territory. It is advisable to concentrate the flow of patients affected by this condition in a few hospitals with surgical teams specifically trained in PAS, availability of specialized resources, and institutional efforts at improving quality of care with the aim of achieving better health outcomes in pregnant women with this condition. To achieve this goal, participants recommend that healthcare regulatory agencies at a national and regional level should oversee the process of referral for these patients, expediting administrative pathways in those cases in which there is no prior agreement between the insurer and the selected hospital or clinic. Recommendation 3. Referral centers for patients with PAS are urged to build teams consisting of a fixed group of specialists (obstetricians, urologists, general surgeons, interventional radiologists) entrusted with the care of all PAS cases. It is advisable for these interdisciplinary teams to use the "intervention bundle" model as a guidance for building PAS referral centers. This model comprises the following activities: service preparedness, disease prevention and identification, response to the occurrence of the disease, and debriefing after every event. Telemedicine facilitates PAS treatment and should be taken into consideration by interdisciplinary teams caring for this disease. Recommendation 4. Obstetrics residents must be instructed in the performance of maneuvers that are useful for the prevention and treatment of massive intraoperative bleeding due to placenta praevia and PAS, including manual aortic compression, uterine tourniquet, pelvic packing, retrovesical bypass, and Ward maneuver. Specialization Obstetrics and Gynecology programs in Colombia must include the basic concepts of the diagnosis and treatment of PAS. Referral centers for PAS must offer online and in-person training programs for professionals interested in improving their competencies in PAS. Moreover, they must offer permanent remote support (telemedicine) to other hospitals in their region for patients with this condition. Recommendation 5. Patients suspected of having PAS and placenta praevia based on imaging, with no evidence of active vaginal bleeding, must be delivered between weeks 34 and 36 6/7. Surgical treatment must include sequential interventions that may vary depending on the characteristics of the lesion, the clinical condition of the patient and the availability of resources. The surgical options (total and subtotal hysterectomy, one-stage conservative surgical management and watchful waiting) must be included in a protocol known by the entire interdisciplinary team. In situations in which an antepartum diagnosis is lacking, that is to say, in the face of intraoperative finding of PAS (evidence of purple bulging or neovascularization of the anterior aspect of the uterus), and the participation of untrained personnel, three options are considered: Option 1: In the absence of indication of immediate delivery or of vaginal delivery, the recommendation is to postpone the cesarean section (close the laparotomy before incising the uterus) until the recommended resources for safe surgery are secured. Option 2: If there is an indication for immediate delivery (e.g., non-reassuring fetal status) but there is absence of vaginal bleeding or indication for immediate PAS management, a two-stage management is suggested: cesarean section avoiding placental incision, followed by uterine repair and abdominal closure, until the availability of the recommended resources for safe surgery is ascertained. Option 3: In the event of vaginal bleeding that prevents definitive PAS management, the fetus must be delivered through the uterine fundus, followed by uterine repair and reassessment of the situation. Sometimes, fetal delivery diminishes placental flow and vaginal bleeding is reduced or disappears, enabling the possibility to postpone definitive management of PAS. In case of persistent significant bleeding, hysterectomy should be performed, using all available resources: manual aortic compression, immediate call to the surgeons with the best available training, telemedicine support from expert teams in other hospitals. If a patient with risk factors for PAS (e.g., myomectomy or previous cesarean section) has a retained placenta after vaginal delivery, it is advisable to confirm the possibility of such diagnosis (by means of ultrasound, for example) before proceeding to manual extraction of the placenta. It is our hope that this first Colombian consensus on PAS will serve as a basis for additional discussions and collaborations that can result in improved clinical outcomes for women affected by this condition. Additional research will be required in order to evaluate the applicability and effectiveness of these recommendations.


Search for cis-acting factors and maternal effect variants in Silver-Russell patients with ICR1 hypomethylation and their mothers.
Silver-Russell syndrome is an imprinting disorder characterized by severe intrauterine and postnatal growth retardation. The majority of patients show loss of methylation (LOM) of the H19/IGF2 IG-DMR (ICR1) in 11p15.5. In ~10% of these patients aberrant methylation of additional imprinted loci on other chromosomes than 11 can be observed (multilocus imprinting defect - MLID). Recently, genomic variations in the ICR1 have been associated with disturbed methylation of the ICR1. In addition, variants in factors contributing to the life cycle of imprinting are discussed to cause aberrant imprinting, including MLID. These variants can either be identified in the patients with imprinting disorders themselves or in their mothers. We performed comprehensive studies to elucidate the role of both cis-acting variants in 11p15.5 as well as of maternal effect variants in the etiology of ICR1 LOM. Whereas copy number analysis and next generation sequencing in the ICR1 did not provide any evidence for a variant, search for maternal effect variants in 21 mothers of patients with ICR1 LOM identified two carriers of NLRP5 variants. By considering our results as well as those from the literature, we conclude that the causes for epimutations are heterogeneous. MLID might be regarded as an own etiological subgroup, associated with maternal effect variants in NLRP and functionally related genes. In addition, these variants might also contribute to LOM of single imprinted loci. Furthermore, genomic variants in the patients themselves might result in aberrant methylation patterns and need further investigation.


Increase in the duration of antidepressant treatment from 1994 to 2003: a nationwide population-based study from Finland.
We examined the length and continuity of antidepressant treatment and factors associated with long-term of treatment among adults. Nationwide data from all reimbursed antidepressant prescriptions in 1994-2003 were linked with patients' data retrieved from Statistics Finland and the Finnish Hospital Discharge Register. Logistic regression models were used to analyse long term use of antidepressants. The annual prevalence of antidepressant use increased from 3.6% in 1994 to 7.3% in 2003. Short-term use (<3 months) decreased from 58% in 1995 to 51% in 2000 and long-term treatment (≥12 months) increased from 18 to 21%. In 2000, 31% of treatment periods lasted ≥6 months and 24% ≥9 months. Long-term treatment correlated to the purchase of other psychotropics, in-patient psychiatric care, and prescription by a psychiatrist. Treatment periods with antidepressants have become longer over time. Clinical factors related to mental disorder severity predict long-term use. Only a quarter had the treatment duration recommended by clinical guidelines for depression.


Expression of the histidine operon in rho mutants of Escherichia coli.
Expression of the Escherichia coli histidine operon was measured in four independently isolated sets of strains carrying ten different rho mutations. Rho factor does not act as a major regulatory element of histidine operon attenuation.


Exogastrulation and interference with the expression of major yolk protein by estrogens administered to sea urchins.
Although estrogens have been detected in some echinoderm species, their role is not clearly understood; so we examined the effects of estrogens administered to sea urchin embryos and larvae. A typical malformation was exogastrulation, induced by the exposure to ethynylestradiol (EER) in a defined period of 12 h from 12 h after fertilization (HAF). Morphogenesis for gastrulation was delayed in the treated embryos: protrusion of the archenteron started at 30 HAF when gastrulation had already finished in normal embryos. Exogastrulation induced by EER was cancelled by the antiestrogen chemical, ICI182,780. Feeding larvae were less sensitive to estrogens than those in early embryogenesis and, at certain concentrations, developed without abnormal morphology. The effect of estrogens was examined at the level of gene expression of the major yolk protein (MYP). MYP expression started during the larval stage and was suppressed by estrone at the six-armed stage, but not by beta-estradiol, and in later stage larvae, the expression was not affected by treatment with either estrogen. Estrogens affect sea urchins in the early stage of embryogenesis, leading to abnormal morphogenesis and interference with gene expression.


Differences in mouse strains determine the outcome of Der p 2 allergy induction protocols.
In vivo animal models can provide worthy information on various aspects of asthma mechanism and pathogenesis. The genetic predisposition and phenotype of mice may affect the immune response itself. Here we compare the early immune response to Der p 2 or HDM allergen extract upon injection and inhalation in BALB/c and C57BL/6 mice. Female C57BL/6 and BALB/c mice were immunized with Der p 2 allergen subcutaneously followed by inhalation of Der p 2 or HDM extract. After challenge, the mice were euthanized; blood, bronchoalveolar lavage (BAL), spleens and lungs were collected. Cells from BAL were identified by May-Grünwald Giemsa staining and lung leukocyte populations were analyzed by flow cytometry. Serum antibody levels of Der p 2 specific IgE, IgG, IgG1 and IgG2a were assessed by ELISA, and cytokine secretion (IL-4, IFN-γ and IL-10) was evaluated upon stimulation with Der p 2 or HDM extract. The Th2 immune response was confirmed by elevated allergen-specific immunoglobulin E (IgE) and the allergic reaction was evidenced by infiltration of eosinophils and/or neutrophils into BAL. We found that BALB/c mice were inefficient in integrating local with systemic immune response, evidenced by almost no IgG or IgE production upon one subcutaneous injection and subsequent inhalation of Der p 2 allergen; also, the bronchoalveolar lavage infiltrate in these mice consisted of neutrophil infiltration, unlike C57BL/6 mice in which eosinophilic infiltrate predominated. The differences between BALB/c and C57BL/6 mice strains could be exploited for generating different types of responses to the Der p 2 allergen.


Acupuncture for patients with chronic pruritus: protocol of a systematic review and meta-analysis.
Chronic pruritus (CP) frequently occurs in many skin and systemic diseases, and adversely affects quality of life. This systematic review aims to evaluate treatment effects of acupuncture on CP. An electronic and manual search will be conducted for all acupuncture treatments for CP, from the inception date of predefined database up to 28 February 2020. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database and the Wanfang Database. Other sources, including existing systematic reviews, conference proceedings and reference lists of identified publications will also be searched. Additionally, any clinical randomised controlled trials related to acupuncture treatment for CP, regardless of the publication status and language limitations, will be included. Study selection, data extraction and research quality assessments will be conducted independently by two researchers. The primary outcome measures include the Visual Analogue Scale, Urdu 5D-Itch Scale or other validated scales implemented after at least 2 weeks of treatment. Secondary outcomes include the effective rate, Quality of Life Scale (eg, the EQ-5D third level, the Dermatology Life Quality Index, etc.), Pittsburgh Sleep Quality Index, recurrence rate during the follow-up period and adverse events. If possible, meta-analyses will be performed using RevMan V.5.3 statistical software; otherwise, a descriptive analysis or subgroup analysis will be conducted. The results will be presented as the risk ratio of the binary data and the mean difference (MD) or standardised MD of the continuous data. This systematic review protocol does not require formal ethical approval because the data are not personalised. It will be published in peer-reviewed journals and presented at international academic conferences. CRD42019136727.


Coagulation activation and hyperviscosity in infection.
A serial study of coagulation activation and whole-blood viscosity was performed on 37 patients with local or systemic bacterial infection, malaria, or a viral infection. Thrombocytopenia, without consumption of coagulation factors, was the main feature of benign tertian malaria and viral infection, whereas in septicaemia and malignant tertian malaria it was associated with activation of coagulation and fibrinolysis. Patients with evidence of intravascular coagulation showed the highest levels of factor VIII related antigen which did not correlate with fibrinogen and probably reflected vascular endothelial cell damage rather than an acute-phase protein reaction. Hyperviscosity, which has been implicated in the pathogenesis of endotoxic shock and cerebral malaria, occurred in parallel with the acute-phase rise in plasma fibrinogen. There was, however, no evidence to implicate hyperviscosity as a major causative factor in the pathogenesis of septic shock or severe infective illness.


Specificity of ethylcholine mustard aziridinium as an irreversible inhibitor of choline transport in cholinergic and noncholinergic tissue.
The sensitivity of choline transport to inhibition by ethylcholine mustard aziridinium (ECMA) was studied in several tissues. Choline transport was found to be inhibited irreversibly by ECMA in guinea pig and rat synaptosomes but not inhibited in erythrocytes or kidney slices. If this finding can be extended to other tissues ECMA sensitivity may provide a simple criterion for identifying the choline carrier associated with cholinergic tissue.


Associated medical conditions among 10-year-old children with oral clefts - a retrospective review across three cleft centres: Part 2.
Introduction In many cases, children with oral clefts present with accompanying medical conditions. These associated conditions can add complexity to the patient's dental management, both in terms of their treatment need and risk. Recognition and careful consideration of associated medical conditions is therefore crucial in providing safe and effective care for these patients.Aim This paper is the second in a two-part three-centre series. It investigates the prevalence of medical conditions affecting cleft lip and/or palate patients attending three cleft units within the UK.Method Retrospective review was undertaken within three cleft units: South Wales (SW), Cleft NET East (CNE) and West Midlands (WM). This was completed via assessment of the 10-year audit record appointment clinical notes for the year 2016/2017.Results In total, 144 cases were reviewed (SW = 42; CNE = 52; WM = 50). Of these, 38.9% of patients (n = 56) had associated medical conditions recorded.Discussion The review highlights the variety and impact of medical conditions affecting UK cleft patients providing insight into the consequent complexity of their dental care.Conclusion An awareness of cleft lip and/or palate patients' associated medical conditions is important for all health care professionals involved in their care. Indeed, understanding of the patient's medical needs by multidisciplinary cleft teams is essential for effective planning and completion of holistic care. Involvement of specialists in paediatric dentistry sharing care with general dental practitioners is vital in providing appropriate oral health care and preventive support.


Corrigendum: Effect of Carbon Ion Radiation Induce Bystander Effect on Metastasis of A549 Cells and Metabonomic Correlation Analysis.
[This corrects the article DOI: 10.3389/fonc.2020.601620.].


Trends Analysis of rhBMP Utilization in Single-Level Posterior Lumbar Interbody Fusion in the United States.
Retrospective study. Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been widely used in spinal fusion surgery, but there is little information on rhBMP-2 utilization in single-level posterior lumbar interbody fusion (PLIF). The purpose of our study was to evaluate the trends and demographics of rhBMP-2 utilization in single-level PLIF. Patients who underwent single-level PLIF from 2005 to 2011 were identified by searching ICD-9 diagnosis and procedure codes in the PearlDiver Patient Records Database, a national database of orthopedic insurance records. The year of procedure, age, gender, and region of the United States were recorded for each patient. Results were reported for each variable as the incidence of procedures identified per 100 000 patients searched in the database. A total of 2735 patients had single-level PLIF. The average rate of single-level PLIF with rhBMP-2 maintained at a relatively stable level (28% to 31%) from 2005 to 2009, but decreased in 2010 (9.9%) and 2011 (11.8%). The overall incidence of single-level PLIF without rhBMP-2 (0.68 cases per 100 000 patients) was statistically higher (P < .01) compared to single-level PLIF with rhBMP-2 (0.21 cases per 100 000 patients). The average rate of single-level PLIF with rhBMP-2 utilization was the highest in West (30.1%), followed by Midwest (26.9%), South (20.5%), and Northeast (17.8%). The highest incidence of single-level PLIF with rhBMP-2 was observed in the age group <65 years (0.3 per 100 000 patients). To our knowledge, this is the first study to report on the demographics associated with rhBMP-2 use in single-level PLIF. There was a 3-fold increase in the rate of PLIF without rhBMP-2 compared to PLIF with rhBMP-2, with both procedures being mainly done in patients less than 65 years of age.


On Collective Molecular Dynamics in Biological Systems: A Review of Our Experimental Observations and Theoretical Modeling.
We review processes by which different sounds, such as meditation music, mantra, kindness, or hatred expressions, and noises induce responses from cells and their components. We define 'good' or 'bad' sounds as those enhancing or inhibiting the cell's biological activity, respectively. It is highlighted that the cellular dynamics results in a coherent organization with the formation of ordered patterns due to long-range correlations among the system constituents. Due to coherence, in the framework of quantum field theory, extended domains become independent of quantum fluctuations. Non-dissipative energy transfer on macromolecule chains is briefly discussed. Observed fractal features are analyzed by the fast Fourier transform and a linear relationship between logarithms of conjugate variables is observed. The fractal relation to the generation of forms (morphogenesis) and to the transition from form to form (metamorphosis) is commented. The review is also motivated by the suggestions coming from the cells' responses, which show their ability to move from the syntactic level of the sound component frequencies to the semantic level of their collective envelope. The process by which sounds are selected to be good or bad sounds sheds some light on the problem of the construction of languages.


A photoelastic study of the hip nail-plate in unstable trochanteric fractures. A biomechanical study of unstable trochanteric fractures II.
The photoelastic technique was applied to acrylic models of unstable trochanteric fractures. Model osteosynthesis was performed on nail-plates with different angles. An increase of the angle between the nail and plate was shown to reduce the shear force between those two components considerably. From mecnanical considerations it is recommended that a steep placement of the nail-plate is advantageous in osteosynthesis of unstable trochanteric fractures without medial support.


Simultaneous measurement of neutrophil, lymphocyte, and monocyte glutathione by flow cytometry.
A flow cytometric method for quantitation of glutathione (GSH) was applied to simultaneous analysis of the major leukocyte types in peripheral blood. Cellular thiols (predominantly GSH) were stained with monochlorobimane (MCIB), and thiol fluorescence was measured with a flow cytometer. The fluorescence of the thiols closely reflected the GSH content, as measured by a specific glutathione reductase assay. Fluorescence of individual cell types could be measured after delineating those cells by their light-scatter characteristics, utilizing dual-angle light scatter for discrimination. By this means, GSH contents of 12.5 +/- 2.0 nmol/10(7) neutrophils, 14.5 +/- 2.7 nmol/10(7) monocytes, and 5.0 +/- 1.0 nmol/10(7) lymphocytes were found. The results obtained for neutrophils with the flow cytometer were virtually identical with those obtained with chemical assay in purified samples of neutrophils, indicating the validity of the flow cytometric method.


Utilization of swine to study the risk factor of an elevated salt diet on blood pressure.
Two homogeneous groups of castrated swine were fed identical diets except that one contained an increased sodium chloride content. The diets were initiated at weaning age and the blood pressure of the pig was followed for 8 months. Blood pressures were measured with an automatic blood pressure recorder for a 1-week period every 4th week. At the end of 8 months, the group on the high salt diet had blood pressure elevated above that of the group on the low salt diet.


Pure nongestational choriocarcinoma of ovary.
Primary ovarian choriocarcinoma arising presumably from a germ cell is extremely rare. Besides arising gestationally or nongestationally, it may be pure or mixed with other germ cell tumors like immature teratoma, dysgerminoma, polyembryoma. We present a case of a 22-year-old woman diagnosed with pure nongestational choriocarcinoma of the ovary with a review of the literature and discussion of its origin.


High performance liquid chromatography-tandem mass spectrometric determination of rupatadine in human plasma and its pharmacokinetics.
A simple, rapid, sensitive and selective liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the quantification of rupatadine in human plasma using estazolam as internal standard (IS). Following liquid-liquid extraction, the analytes were separated using a mobile phase of methanol-ammonium acetate (pH 2.2; 5mM) (50:50, v/v) on a reverse phase C18 column and analyzed by a triple-quadrupole mass spectrometer in the positive ion and multiple reaction monitoring (MRM) mode, m/z 416-->309 for rupatadine and m/z 295-->267 for the IS. The assay exhibited a linear dynamic range of 0.1-100 ng/ml for rupatadine in human plasma. The lower limit of quantification (LLOQ) was 0.1 ng/ml with a relative standard deviation of less than 20%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated LC-MS/MS method has been successfully applied to study the pharmacokinetics of rupatadine in healthy volunteers.


High power, compact, picosecond MOPA based on single trench fiber with single polarized diffraction-limited output.
We experimentally demonstrate an all-solid Yb-doped 30 μm core diameter single trench fiber. Measurements ensure a robust effective single-mode operation without the need of tight coiling as required for conventional fibers thanks to the ultralow NA (∼0.038) and resonant ring surrounding the core. All-solid and cylindrical design ensures the suitability for mass scale production with the added benefit of all-fiberized device structure. A compact master oscillator power amplifier (MOPA) has been built using this fiber delivering ∼23.5 ps pulses at 13.5 MHz repetition rate delivering up to ∼52 W of average output power corresponding to a pulse energy of ∼3.8 μJ and peak power of >160 kW, while maintaining ∼76% slope efficiency. The output beam exhibits a polarization extinction ratio of more than 15 dB and a M2 less than 1.15.


Gonadal function and testicular histology in males with Prader-Willi syndrome.
Cryptorchidism is common in Prader-Willi syndrome (PWS) males, but the testicular histology in childhood remains uncertain. The association between testicular histology and long-term gonadal function in PWS males is also unknown. To evaluate the relationship between testicular histology in childhood and long-term gonadal function in PWS males. Forty men with PWS were assessed longitudinally at our institute over the past 24 years. Clinical examinations and blood tests for LH, FSH and testosterone levels were compared with normal reference values. Tissue specimens were collected during orchiopexy and analyzed based on Nistal categories. Of nine testes available for pathological assessments, two showed favourable histology (Nistal I) and seven showed unfavourable histology (Nistal II or III). Of five postpubertal males with histology available, four reached puberty spontaneously, but only one reached Tanner stage 5. In a male with favourable histology, LH and FSH were high, but testosterone was normal, though below the average of the reference range. In three males with unfavourable histology, LH was normal, but FSH was highly elevated, and testosterone was at the lower limit of normal. One patient took hCG treatment to induce puberty; this patient showed favourable histology, but LH, FSH and testosterone were not elevated in adolescence. Testicular histology of PWS men in childhood varies from normal to Sertoli Cell-Only Syndrome. Regardless of the testicular histology in childhood, hypogonadism in PWS adults arises as a consequence of primary testicular dysfunction with highly elevated FSH and insufficient testosterone levels.


Soil carbon and associated bacterial community shifts driven by fine root traits along a chronosequence of Moso bamboo (Phyllostachys edulis) plantations in subtropical China.
Moso bamboo (Phyllostachys edulis) is widely considered to be effective in capturing and sequestering atmospheric C, but the long-term effects of extensive management strategies on soil organic carbon (SOC), bacterial communities, fine root (FR, ø ≤ 2 mm) traits, and their inherent connection remain unclear. In this study, we simultaneously measured the SOC content of the bulk and rhizosphere soil fractions, the aggregate stability, the chemical composition of SOC (solid-state 13C nuclear magnetic resonance [NMR]), the bacterial community structure in the rhizosphere, and the FR morphological traits including biomass, specific root length (SRL), and root length density (RLD) along a chronosequence (stand age of 19, 37, and 64 years) of extensively managed Moso bamboo plantations and in an adjacent secondary forest as a control. The organic C content in both the rhizosphere and bulk soil increased rapidly with plantation age in the 0-20- and 20-40-cm soil layers, accompanied by an increase in the aggregate stability. FR traits including biomass, SRL, and RLD also increased continuously in response to soil C:N:P stoichiometry. All of these traits were significantly correlated with SOC, occluded particulate organic C (oPOC), and mineral-associated organic C (MOC), suggesting that FR traits could drive the soil C sequestration with the plantation age. Further analysis indicated that the microbial biomass C (MBC) content, MBC/total organic carbon (TOC) ratio, and bacterial abundance decreased with the plantation age, and the shift from soil oligotrophy to copiotrophy bacteria were mainly driven by changes in FR traits and SOC properties. Such a reassembly of bacterial communities combined with an increase in root biomass is favorable for the accumulation of stable C functional groups (alkyl C or aromatic C). Our findings indicate that extensive management regimes of Moso bamboo plantations could promote long-term soil C sequestration especially in the rhizosphere by promoting the formation of soil aggregates and organic-mineral complexes and by shifting bacterial community composition, and that these changes can be inferred through changes in the FR traits.


An unusual complication following surgical treatment of deQuervain's disease.
Symptoms of deQuervain's disease were relieved by incision of the first dorsal compartment sheath in a 43-year-old hospital employee. Three months after the operation she developed dysaesthesias in the distribution of the superficial radial nerve with wrist extension and thumb abduction. At reoperation the tendons of the first dorsal compartment were found to glide dorsally onto a fibrous remnant of the sheath and to elevate the overlying superficial radial nerve. Excision of the fibrous ridge resulted in relief of symptoms. The complication could have been avoided, in retrospect, by excising the sheath or by incising it at its dorsal attachment.


ViVGG19: Novel exemplar deep feature extraction-based shoulder rotator cuff tear and biceps tendinosis detection using magnetic resonance images.
Rotator cuff tear (RCT) and biceps tendinosis (BT) are the two most common shoulder disorders worldwide. These disorders can be diagnosed using magnetic resonance imaging (MRI), but the expert interpretation is manual, time-consuming, and subjected to human errors. Therefore, a fixed-size feature extraction model was created to objectively and accurately perform automated binary classification of RCT vs. normal and BT vs. normal on MRI images. We have developed an exemplar deep feature extraction model to diagnose RCT and BT disorders. The model was tested on a new MR image dataset comprising transverse, sagittal, and coronal MRI images of the shoulder that had been organized into three cases. BT was studied on transverse MRI images (Case 1), while RCT was studied on sagittal (Case 2) and coronal MRI images (Case 3). Our model comprised deep feature generation using a pre-trained VGG19, feature selection using iterative neighborhood component analysis (INCA), and classification using shallow standard classifiers k-nearest neighbors (KNN), support vector machine (SVM), and artificial neural network (ANN). In the feature extraction phase, two fully connected layers were used to extract deep features from the original image, and sixteen fixed-size patches obtained by the division of the original image. This model was named Vision VGG19 (ViVGG), analogous to vision transformers (ViT). The feature vector is extracted from the raw image dataset, and 16 feature vectors are extracted from each fixed-size patch. Seventeen feature vectors obtained from each image are obtained from fc6 and fc7 layers of the pre-trained VGG19, are merged to obtain final feature vector. INCA was used to choose the top features from the created features, and the chosen features were classified using shallow classifiers. We defined three cases to evaluate the proposed ViVGG19 to diagnose RT and BCT disorders. Our proposed ViVGG19 model achieved more than 99% accuracy using the KNN classifier. ViVGG19 is a very effective model for detecting RCT and BT disorders on shoulder MRI images. The developed automated system is ready to be tested with a bigger diverse database obtained from different medical centers.


Psychosocial predictors of fruit and vegetable consumption in adults a review of the literature.
Adequate fruit and vegetable intake has been found to promote health and reduce the risk of several cancers and chronic diseases. Understanding the psychological determinants of fruit and vegetable intake is needed to design effective intervention programs. Papers published in English from 1994 to 2006 that described the relationship between psychosocial predictors and fruit and vegetable intake in adults were reviewed. Studies and their constructs were independently rated based on the direction of significant effects, quality of execution, design suitability, and frequency. Methodology from the Guide to Community Preventive Services was used to systematically review and synthesize findings. Twenty-five psychosocial constructs spanning 35 studies were reviewed (14 prospective and 21 cross-sectional/descriptive studies). Strong evidence was found for self-efficacy, social support, and knowledge as predictors of adult fruit and vegetable intake. Weaker evidence was found for variables including barriers, intentions, attitudes/beliefs, stages of change, and autonomous motivation. The findings underscore the need to design future behavioral interventions that use strong experimental designs with efficacious constructs and to conduct formal mediation analyses to determine the strength of these potential predictors of fruit and vegetable intake.


The center of the emotional universe: Alcohol, stress, and CRF1 amygdala circuitry.
The commonalities between different phases of stress and alcohol use as well as the high comorbidity between alcohol use disorders (AUDs) and anxiety disorders suggest common underlying cellular mechanisms governing the rewarding and aversive aspects of these related conditions. As an integrative center that assigns emotional salience to a wide variety of internal and external stimuli, the amygdala complex plays a major role in how alcohol and stress influence cellular physiology to produce disordered behavior. Previous work has illustrated the broad role of the amygdala in alcohol, stress, and anxiety. However, the challenge of current and future studies is to identify the specific dysregulations that occur within distinct amygdala circuits and subpopulations and the commonalities between these alterations in each disorder, with the long-term goal of identifying potential targets for therapeutic intervention. Specific intra-amygdala circuits and cell type-specific subpopulations are emerging as critical targets for stress- and alcohol-induced plasticity, chief among them the corticotropin releasing factor (CRF) and CRF receptor 1 (CRF1) system. CRF and CRF1 have been implicated in the effects of alcohol in several amygdala nuclei, including the basolateral (BLA) and central amygdala (CeA); however, the precise circuitry involved in these effects and the role of these circuits in stress and anxiety are only beginning to be understood.


Inducing regulated necrosis and shifting macrophage polarization with anti-EMMPRIN antibody (161-pAb) and complement factors.
Treatment of solid tumors is often hindered by an immunosuppressive tumor microenvironment (TME) that prevents effector immune cells from eradicating tumor cells and promotes tumor progression, angiogenesis, and metastasis. Therefore, targeting components of the TME to restore the ability of immune cells to drive anti-tumoral responses has become an important goal. One option is to induce an immunogenic cell death (ICD) of tumor cells that would trigger an adaptive anti-tumoral immune response. Here we show that incubating mouse renal cell carcinoma (RENCA) and colon carcinoma cell lines with an anti-extracellular matrix metalloproteinase inducer polyclonal antibody (161-pAb) together with complement factors can induce cell death that inhibits caspase-8 activity and enhances the phosphorylation of receptor-interacting protein kinase 3 (RIPK3) and mixed-lineage kinase-like domain (MLKL). This regulated necrotic death releases high levels of dsRNA molecules to the conditioned medium (CM) relative to the necrotic death of tumor cells induced by H2 O2 or the apoptotic death induced by etoposide. RAW 264.7 macrophages incubated with the CM derived from these dying cells markedly enhanced the secretion of IFNβ, and enhanced their cytotoxicity. Furthermore, degradation of the dsRNA in the CM abolished the ability of RAW 264.7 macrophages to secrete IFNβ, IFNγ-induced protein 10 (IP-10), and TRAIL. When mice bearing RENCA tumors were immunized with the 161-pAb, their lysates displayed elevated levels of phosphorylated RIPK3 and MLKL, as well as increased concentrations of dsRNA, IFNβ, IP-10, and TRAIL. This shows that an antigen-targeted therapy using an antibody and complement factors that triggers ICD can shift the mode of macrophage activation by triggering regulated necrotic death of tumor cells.


Physical function and quality of life in patients with chronic GvHD: a summary of preclinical and clinical studies and a call for exercise intervention trials in patients.
Allogeneic hematopoietic stem cell transplant, to reconstitute the hematopoietic and immune status of patients undergoing myeloablative therapy for hematologic disorders, has been of great benefit in minimizing or eradicating disease and extending survival. Patients who undergo allogeneic hematopoietic stem cell transplant (allo-HSCT) are subject to many comorbidities among which the most significant, affecting quality of life (QoL) and survival, are acute GvHD (aGvHD) and chronic GvHD (cGvHD), resulting from donor lymphocytes reacting to and damaging host tissues. Physical activity and exercise have clearly been shown, in both children and adults, to enhance fitness, improve symptomatology and QoL, reduce disease progression and extend survival for many diseases including malignancies. In some cases, vigorous exercise has been shown to be equal to or more effective than pharmacologic therapy. This review addresses how cGvHD affects patients' physical function and physical domain of QoL, and the potential benefits of exercise interventions along with recommendations for relevant research and evaluation targeted at incorporating this strategy as soon as possible after allo-HSCT and ideally, as soon as possible upon diagnosis of the condition leading to allo-HSCT.


The International Conference on Intelligent Biology and Medicine (ICIBM) 2016: from big data to big analytical tools.
The 2016 International Conference on Intelligent Biology and Medicine (ICIBM 2016) was held on December 8-10, 2016 in Houston, Texas, USA. ICIBM included eight scientific sessions, four tutorials, one poster session, four highlighted talks and four keynotes that covered topics on 3D genomics structural analysis, next generation sequencing (NGS) analysis, computational drug discovery, medical informatics, cancer genomics, and systems biology. Here, we present a summary of the nine research articles selected from ICIBM 2016 program for publishing in BMC Bioinformatics.


[Parkinson's disease: what gets in the way of the partnership relationship?].
What difficulties do patients face in being considered as players in their own treatment pathway? What obstacles do they have to overcome to participate in making decisions concerning them? How do they live the patient-caregiver relationship, sometimes felt to be unequal? Here are a few stories from patients with Parkinson's disease.


T-and B-lymphocyte subsets in patients with Dupuytren's disease. Correlations with disease severity.
Previous reports have indicated that inflammatory mechanisms may be involved in the pathogenesis of Dupuytren's disease and it has even been suggested that this condition is a T-cell mediated autoimmune disorder. We investigated peripheral blood lymphocyte subsets from 21 patients with Dupuytren's disease and compared them with ten healthy blood donors. The Dupuytren's patients had an increase in DR+ T-cells compared with healthy controls. Furthermore, patients with both palmar and plantar involvement had a higher percentage of DR+ T-cells than those with only the palm affected. The percentage of circulating CD5+ B-cells was lower in the Dupuytren's patients compared with the control group; this feature was marginally significant for the whole group of Dupuytren's patients but was strongest in the group of patients with both palmar and plantar involvement. These findings support previous suggestions that immunological mechanisms, involving activated T-cells and probably also B-cells, are involved in the pathogenesis of Dupuytren's disease.


Characteristics of long-term changes in microbial communities from contaminated sediments along the west coast of South Korea: Ecological assessment with eDNA and physicochemical analyses.
The environmental DNA (eDNA) metabarcoding was applied to assess benthic ecological health in the west coast of South Korea by investigating a long-term microbial community change (2015-17). The ecological interaction among microorganisms, from phylum to family level, and their associations to environmental variables across the five regions were highlighted. As part of the study, the available chemistry and toxicological data in the regions during the monitoring periods were incorporated into an integrated sediment triad assessment. The bacterial communities were dominated by Proteobacteria (34.2%), Bacteroidetes (13.8%), and Firmicutes (10.8%). Proteobacteria and Bacteroidetes dominated consistently across regions and years, while Firmicutes and Cyanobacteria significantly varied by region and years (p < 0.05). The abundance of this phylum declined over time with the increasing abundance of Cyanobacteria, indicating their independent interactions to certain environmental changes. Planctomycetes and Gemmatimonadetes linked to some contaminants (ΣPAHs and Cu), implying indicator taxa. Overall, eDNA-based microbial community analysis combined with exposures of contaminants and responses of microorganisms is a promising strategy for the assessment of benthic ecological health in contaminated sediments from coastal waters.


Structural insights of a PI3K/mTOR dual inhibitor with the morpholino-triazine scaffold.
Stimulation of the PI3K/Akt/mTOR pathway, which controls cell proliferation and growth, is often observed in cancer cell. Inhibiting both PI3K and mTOR in this pathway can switch off Akt activation and hence, plays a powerful role for modulating this pathway. PKI-587, a drug containing the structure of morpholino-triazines, shows a dual and nano-molar inhibition activity and is currently in clinical trial. To provide an insight into the mechanism of this dual inhibition, pharmacophore and QSAR models were developed in this work using compounds based on the morpholino-triazines scaffold, followed by a docking study. Pharmacophore model suggested the mechanism of the inhibition of PI3Kα and mTOR by the compounds were mostly the same, which was supported by the docking study showing similar docking modes. The analysis also suggested the importance of the flat plane shape of the ligands, the space surrounding the ligands in the binding pocket, and the slight difference in the shape of the binding sites between PI3Kα and mTOR.


Mechanism, assessment and management of pain in chronic pancreatitis: Recommendations of a multidisciplinary study group.
Pain in patients with chronic pancreatitis (CP) remains the primary clinical complaint and source of poor quality of life. However, clear guidance on evaluation and treatment is lacking. Pancreatic Pain working groups reviewed information on pain mechanisms, clinical pain assessment and pain treatment in CP. Levels of evidence were assigned using the Oxford system, and consensus was based on GRADE. A consensus meeting was held during PancreasFest 2012 with substantial post-meeting discussion, debate, and manuscript refinement. Twelve discussion questions and proposed guidance statements were presented. Conference participates concluded: Disease Mechanism: Pain etiology is multifactorial, but data are lacking to effectively link symptoms with pathologic feature and molecular subtypes. Assessment of Pain: Pain should be assessed at each clinical visit, but evidence to support an optimal approach to assessing pain character, frequency and severity is lacking. There was general agreement on the roles for endoscopic and surgical therapies, but less agreement on optimal patient selection for medical, psychological, endoscopic, surgical and other therapies. Progress is occurring in pain biology and treatment options, but pain in patients with CP remains a major problem that is inadequately understood, measured and managed. The growing body of information needs to be translated into more effective clinical care.