Consolidation Treatment for Primary Central Nervous System Lymphoma: Which Modality for Whom?

Abstract: Primary central nervous system lymphoma is a rare aggressive disease that largely affects elderly patients and is associated with poor prognosis. The optimal treatment approach is not yet defined and it consists of induction and consolidation phases. The combination of high-dose (HD) methotrexate-based chemotherapy followed by whole-brain radiotherapy (WBRT) prolongs the median progression-free survival (PFS) and overall survival 2- to 3-fold as compared to WBRT alone but is associated with significant delayed neurotoxicity. Alternative strategies are being investigated in order to improve disease outcomes and spare patients the neurocognitive side effects. These include reduced-dose WBRT, non-myeloablative HD chemotherapy, or HD chemotherapy with autologous stem cell transplantation (HDC/ASCT). There are no randomized studies that compare all these consolidation regimens head to head but recently HDC/ASCT has been evaluated versus WBRT in prospective randomized studies. These studies proved that WBRT and HDC/ASCT yield similar 2-year PFS with preserved or improved cognitive function after HDC/ASCT. Yet, the proportion of patients treated with such intensive consolidation is low, both in real life and in specialized centers, leaving many unsettled issues. This review is appraising current dilemmas related to the choice of consolidating therapeutic modalities, their associated acute and delayed toxicity, and future prospects for alternative approaches in the elderly.

D000971:Antineoplastic Combined Chemotherapy Protocols

D016543:Central Nervous System Neoplasms

Consolidation
Whole-brain radiotherapy
Autologous stem cell transplantation
CNS lymphoma
High-dose chemotherapy
High-dose methotrexate


High True Ileal Digestibility but Not Postprandial Utilization of Nitrogen from Bovine Meat Protein in Humans Is Moderately Decreased by High-Temperature, Long-Duration Cooking.

Abstract:
BACKGROUND
Meat protein digestibility can be impaired because of indigestible protein aggregates that form during cooking. When the aggregates are subsequently fermented by the microbiota, they can generate potentially harmful compounds for the colonic mucosa.

OBJECTIVE
This study evaluated the quantity of bovine meat protein escaping digestion in the human small intestine and the metabolic fate of exogenous nitrogen, depending on cooking processes.

METHODS
Sixteen volunteers (5 women and 11 men; aged 28 ± 8 y) were equipped with a double lumen intestinal tube positioned at the ileal level. They received a test meal exclusively composed of 120 g of intrinsically (15)N-labeled bovine meat, cooked either at 55°C for 5 min (n = 8) or at 90°C for 30 min (n = 8). Ileal effluents and blood and urine samples were collected over an 8-h period after the meal ingestion, and (15)N enrichments were measured to assess the digestibility of meat proteins and the transfer of dietary nitrogen into the metabolic pools.

RESULTS
Proteins tended to be less digestible for the meat cooked at 90°C for 30 min than at 55°C for 5 min (90.1% ± 2.1% vs. 94.1% ± 0.7% of ingested N; P = 0.08). However, the particle number and size in ileal digesta did not differ between groups. The appearance of variable amounts of intact fibers was observed by microscopy. The kinetics of (15)N appearance in plasma proteins, amino acids, and urea were similar between groups. The amount of exogenous nitrogen lost through deamination did not differ between groups (21.2% ± 0.8% of ingested N).

CONCLUSIONS
Cooking bovine meat at a high temperature for a long time can moderately decrease protein digestibility compared with cooking at a lower temperature for a short time and does not affect postprandial exogenous protein metabolism in young adults. The study was registered at www.clinicaltrials.gov as NCT01685307.

Oberli|Marion|M| Marsset-Baglieri|Agnès|A| Airinei|Gheorghe|G| Santé-Lhoutellier|Véronique|V| Khodorova|Nadezda|N| Rémond|Didier|D| Foucault-Simonin|Angélique|A| Piedcoq|Julien|J| Tomé|Daniel|D| Fromentin|Gilles|G| Benamouzig|Robert|R| Gaudichon|Claire|C|

digestion
postprandial
protein metabolism
healthy volunteers
stables isotopes


Beyond infertility: obstetrical and postpartum complications associated with endometriosis and adenomyosis.

Abstract: The risk of pregnancy and neonatal complications in women with endometriosis and adenomyosis is debatable. A literature review looking at rates, presentation, and management of spontaneous hemoperitoneum, enlargement, abscess, and rupture of an endometrioma, uterine rupture, and bowel perforation in pregnant women with endometriosis was conducted. Moreover, studies addressing differences in early pregnancy (miscarriage), late pregnancy (gestational diabetes mellitus, preeclampsia, prematurity, placenta previa, placental abruption, cesarean section, hemorrhages) and neonatal outcomes (weight at birth) between endometriosis and adenomyosis patients versus control subjects were reviewed. The overall prevalence of endometriosis-related spontaneous hemoperitoneum in pregnancy is estimated to be ∼0.4%. Only four cases of endometrioma rupture in pregnancy have been reported. Although during pregnancy there is no way to anticipate the onset of complications from preexisting endometriosis, it is important, when a specific abdominal pain occurs, to suspect rare but potentially life-threating events. Population-based studies suggest a possible association of endometriosis with preterm birth and placenta previa. Limits of the published studies are noted and discussed.

complication
Endometriosis
adenomyosis
pregnancy
placenta previa
preterm birth


Interval-valued belief entropies for Dempster-Shafer structures.

Abstract: In practical application problems, the uncertainty of an unknown object is often very difficult to accurately determine, so Yager proposed the interval-valued entropies for Dempster-Shafer structures, which is based on Dempster-Shafer structures and classic Shannon entropy and is an interval entropy model. Based on Dempster-Shafer structures and classic Shannon entropy, the interval uncertainty of an unknown object is determined, which provides reference for theoretical research and provides help for industrial applications. Although the interval-valued entropies for Dempster-Shafer structures can solve the uncertainty interval of an object very efficiently, its application scope is only a traditional probability space. How to extend it to the evidential environment is still an open issue. This paper proposes interval-valued belief entropies for Dempster-Shafer structures, which is an extension of the interval-valued entropies for Dempster-Shafer structures. When the belief entropy degenerates to the classic Shannon entropy, the interval-valued belief entropies for Dempster-Shafer structures will degenerate into the interval-valued entropies for Dempster-Shafer structures. Numerical examples are applied to verify the validity of the interval-valued belief entropies for Dempster-Shafer structures. The experimental results demonstrate that the proposed entropy can obtain the interval uncertainty value of a given uncertain object successfully and make decision effectively.

Belief entropy
Uncertainty
Interval-valued entropies
Shannon entropy
Dempster–Shafer structures


Use of fingolimod in patients with relapsing remitting multiple sclerosis in Kuwait.

Abstract:
BACKGROUND
Post-marketing studies are important to confirm what was established in clinical trials, and to assess the intermediate and long-term efficacy and safety.

OBJECTIVE
To assess efficacy and safety of fingolimod in multiple sclerosis (MS) in Kuwait.

METHODS
We retrospectively evaluated MS patients using the MS registries in 3 MS clinics. Relapsing remitting MS patients according to revised 2010 McDonald criteria who had been treated with fingolimod for at least 12 months were included. Primary endpoint was proportion of relapse-free patients at last follow-up. Secondary endpoints were mean change in EDSS and proportion of patients with MRI activity (gadolinium-enhancing or new/enlarging T2 lesions).

RESULTS
76 patients met the inclusion criteria. Mean age and mean disease duration were 34.43 and 7.82 years respectively. Mean duration of exposure to fingolimod was 18.50 months. Proportion of relapse-free patients was 77.6% at last follow-up. Mean EDSS score significantly improved (2.93 versus 1.95; p<0.0001) while 17.1% of patients continued to have MRI activity versus 77.6% at baseline (p<0.0001). Four patients stopped fingolimod due to disease breakthrough (n=3) and lymphadenitis (n=1).

CONCLUSION
Fingolimod is safe and effective in reducing clinical and radiological disease activity in relapsing remitting MS patients. Our results are comparable to reported results of phase III studies.

Alroughani|R|R|
Ahmed|S F|SF|
Behbehani|R|R|
Al-Hashel|J|J|

Fingolimod
Multiple sclerosis
Outcome measures
Treatment


Tau immunotherapy for Alzheimer's disease.

Abstract: Targeting pathological tau protein in Alzheimer's disease (AD) and related tauopathies has shown great potential in animal models. Given that tau lesions correlate better with the degree of dementia than do amyloid-β (Aβ) plaques, their clearance may be clinically more efficacious than removing Aβ when cognitive deficits become evident in AD. Several complementary mechanisms of antibody-mediated removal of tau aggregates are likely to act in concert and the importance of each one may depend on antibody properties, the disease, and its stage. Clinical trials of tau immunotherapy are already underway and several more are likely to be initiated in the near future.

Pedersen|Jan Torleif|JT|
Sigurdsson|Einar M|EM|

immunotherapy
Alzheimer's disease
tau protein
tauopathies


Learning from partnership tensions in transcultural interdisciplinary case discussion seminars: A qualitative study of collaborative youth mental health care informed by game theory.

Abstract: Although collaborative care was adopted in several countries, including Canada, to improve the health and social services system, partnerships are often experienced as challenging. In many cases, transformative partnership remains a political rhetoric rather than a practical reality. This article presents an analysis of partnership relationships in youth mental health (YMH) using insights from game theory and a qualitative analysis of interactions during transcultural interinstitutional and interdisciplinary case discussion seminars (TIICDSs). Drawing on the analysis of 40 seminar sessions and six focus groups with seminar participants conducted in Montréal (Canada) between October 2013 and April 2015, this article interrogates the conditions and processes present in TIICDSs that contribute to building and strengthening YMH partnerships, examining how tensions among TIICDS participants are attended to. Research results indicate that TIICDSs can be seen as a game operating under different rules than real-life clinical work. They are characterized by the establishment of a climate of trust and respect, a high value placed on diversity and creativity, a concern for affects and power dynamics, a process of inclusive dialogue and negotiation, and a consideration for continuity. The game rules allow participants to safely apprehend a situation from a different perspective, a key competence in intercultural and collaborative YMH care. Results also indicate that participants complexify their representations by playing with divergent perceptions of people and situations and that enhanced case formulations are collective game outcomes. In light of our findings, tensions in collaborations can be seen as constituting both obstacles that can be counterproductive if not attended to, as well as powerful and useful learning tools that, under certain conditions, can support the clinical process and contribute to partnership building. Some clinical and partnership impasses may be overcome through clinical case discussions that allow partners to address these tensions and negotiate power relationships.

D000293:Adolescent
D016497:Adolescent Health Services
D003299:Cooperative Behavior
D003431:Cross-Cultural Comparison
D017144:Focus Groups
D005716:Game Theory
D006801:Humans
D033183:Interdisciplinary Communication
D058025:Interdisciplinary Studies
D008605:Mental Health Services
D036301:Qualitative Research
D012947:Social Work

Partnership tensions
Youth mental health
Game theory
Collaborative care
Canada
Intercultural training


Correction of Scanning Electron Microscope Imaging Artifacts in a Novel Digital Image Correlation Framework.

Abstract: The combination of digital image correlation (DIC) and scanning electron microscopy (SEM) enables to extract high resolution full field displacement data, based on the high spatial resolution of SEM and the sub-pixel accuracy of DIC. However, SEM images may exhibit a considerable amount of imaging artifacts, which may seriously compromise the accuracy of the displacements and strains measured from these images. The current study proposes a unified general framework to correct for the three dominant types of SEM artifacts, i.e. spatial distortion, drift distortion and scan line shifts. The artifact fields are measured alongside the mechanical deformations to minimize the artifact induced errors in the latter. To this purpose, Integrated DIC (IDIC) is extended with a series of hierarchical mapping functions that describe the interaction of the imaging process with the mechanics. A new IDIC formulation based on these mapping functions is derived and the potential of the framework is tested by a number of virtual experiments. The effect of noise in the images and different regularization options for the artifact fields are studied. The error in the mechanical displacement fields measured for noise levels up to 5% is within the usual DIC accuracy range for all the cases studied, while it is more than 4 pixels if artifacts are ignored. A validation on real SEM images at three different magnifications confirms that all three distortion fields are accurately captured. The results of all virtual and real experiments demonstrate the accuracy of the methodology proposed, as well as its robustness in terms of convergence.

Maraghechi|S|S|
Hoefnagels|J P M|JPM|
Peerlings|R H J|RHJ|
Rokoš|O|O|
Geers|M G D|MGD|

Imaging artifacts
Scanning electron microscopy
Spatial distortion
Drift distortion
Integrated digital image correlation
Line shift artifacts


Heterotopic Bone Formation 20 Years After Gunshot Wound to the Cervical Spine: A Rare Cause of Progressive Cervical Myelopathy in a Previously Asymptomatic Patient.

Abstract:
BACKGROUND
Gunshot wounds are the most common etiology of penetrating spine injuries and have been increasing in incidence in civilian populations. Although these injuries typically result in severe neurologic deficits, operative intervention remains is controversial and is usually reserved for patients with neurologic deterioration, a persistent externalized cerebrospinal fluid fistula, mechanical instability, metallic toxicity, or a bullet location at high risk of migration.

CASE DESCRIPTION
A previously asymptomatic patient who had sustained a gunshot wound to the cervical spine 20 years previously presented with new-onset progressive myelopathy and radiculopathy secondary to heterotopic ossification (HO) surrounding the retained bullet fragments near the left lateral masses of C5-T1. Computed tomography myelography demonstrated no cranial migration of contrast material past this region of the spine, suggesting severe spinal canal stenosis. Intraoperatively, bullet shrapnel and heterotopic bone fragments were found within the central canal causing compression of the spinal cord. Following decompression and stabilization, the patient had complete resolution of his symptoms and returned to his neurologic baseline. Although HO has been reported as a complication following through and through gunshot wounds, there is a paucity of literature discussing HO formation around retained bullet fragments in the spine.

CONCLUSIONS
HO surrounding retained bullet fragments in the spine is a rare cause of progressive neurologic deterioration following gunshot wounds. Surgical excision of the shrapnel and heterotopic bone can lead to symptomatic relief, and therefore surgery should be considered as a treatment option in carefully selected patients.

Womack|Rachel|R|
Luther|Evan|E|
Perez-Roman|Roberto J|RJ|
Manzano|Glen R|GR|

Gunshot wound
Myelopathy
Radiculopathy
Heterotopic ossification
Retained bullet fragments
Cervical spine injury


Spin-lock MR enhances the detection sensitivity of superparamagnetic iron oxide particles.

Abstract:
PURPOSE
To evaluate spin-lock MR for detecting superparamagnetic iron oxides and compare the detection sensitivity of quantitative T1ρ with T2 imaging.

METHODS
In vitro experiments were performed to investigate the influence of iron oxide particle size and composition on T1ρ . These comprise T1ρ and T2 measurements (B0 = 1.41T) of agar (2%) with concentration ranges of three different iron oxide nanoparticles (IONs) (Sinerem, Resovist, and ION-Micelle) and microparticles of iron oxide (MPIO). T1ρ dispersion was measured for a range of spin-lock amplitudes (γB1 = 6.5-91 kHz). Under relevant in vivo conditions (B0 = 9.4T; γB1 = 100-1500 Hz), T1ρ and T2 mapping of the liver was performed in seven mice pre- and 24 h postinjection of Sinerem.

RESULTS
Addition of iron oxide nanoparticles decreased T1ρ as well as the native T1ρ dispersion of agar, leading to increased contrast at high spin-lock amplitudes. Changes of T1ρ were highly linear with iron concentration and much larger than T2 changes. MPIO did not show this effect. In vivo, a decrease of T1ρ was observed with no clear influence on T1ρ dispersion.

CONCLUSION
By suppression of T1ρ dispersion, iron oxide nanoparticles cause enhanced T1ρ contrast compared to T2 . The underlying mechanism appears to be loss of lock. Spin-lock MR is therefore a promising technique for sensitive detection of iron oxide contrast agents.

Moonen|Rik P M|RP|
van der Tol|Pieternel|P|
Hectors|Stefanie J C G|SJ|
Starmans|Lucas W E|LW|
Nicolay|Klaas|K|
Strijkers|Gustav J|GJ|

D003287:Contrast Media
D003911:Dextrans
D021621:Imaging, Three-Dimensional
D008279:Magnetic Resonance Imaging
D009682:Magnetic Resonance Spectroscopy
D058185:Magnetite Nanoparticles
D008422:Materials Testing
D057054:Molecular Imaging
D015203:Reproducibility of Results
D012680:Sensitivity and Specificity
D013113:Spin Labels

Spin-lock MR
superparamagnetic iron oxide particles
iron oxide nanoparticles
T1ρ dispersion
T1ρ contrast agent
rotating frame relaxation


Accelerated phase chronic myeloid leukemia: evaluation of clinical criteria as predictors of survival, major cytogenetic response and progression to blast phase.

Abstract:
BACKGROUND
Published criteria defining the accelerated phase in chronic myeloid leukemia are heterogeneous and little is known about predictors of poor outcome.

METHODS
This is a retrospective study of 139 subjects in the accelerated phase of chronic myeloid leukemia treated with imatinib at a single center in Brazil. The objective was to identify risk factors for survival, major cytogenetic response and progression to blast phase in this population. The factors analyzed were: blasts 10-29%, basophils≥20%, platelets>1×10(6)/μL or <1×10(5)/μL and white blood cells>1×10(5)/μL in the peripheral blood, as well as clonal evolution, splenomegaly, hemoglobin<10g/dL, time between diagnosis of chronic myeloid leukemia and imatinib treatment, and hematologic toxicity.

RESULTS
Risk factors for poor survival in multivariate analysis were Grades 3-4 hematologic toxicity (p-value=0.001), blasts 10-29% (p-value=0.023), and hemoglobin<10g/dL (p-value=0.04). Risk factors for not achieving major cytogenetic response were blasts 10-29% (p-value=0.007), hemoglobin<10g/dL (p-value=0.001), and previous use of interferon (p-value=0.032). Risk factors for progression to the blast phase were hemoglobin<10g/dL (p-value=0.005), basophils≥20% (p-value=0.023), and time from diagnosis of chronic myeloid leukemia to imatinib treatment>12 months (p-value=0.030).

CONCLUSION
These data indicate that patients with the above risk factors have a worse prognosis. This information can guide the therapy to be used.

Furtado|Vanessa Fiorini|VF|
Santos|Gustavo Rengel|GR|
de Carvalho|Denise Siqueira|DS|
Staziaki|Pedro Vinícius|PV|
Pasquini|Ricardo|R|
Funke|Vaneuza Araújo Moreira|VA|

Accelerated phase
Chronic myeloid leukemia
Imatinib
Mortality
Prognostic factor


A global assessment of knowledge of dental students about nicotine replacement therapy: findings from 43 countries.

Abstract:
OBJECTIVES
Knowledge of nicotine replacement therapy (NRT) is a competency that is expected from receiving training in the treatment for tobacco dependence. This study therefore assessed the knowledge of dental students in 43 countries about NRT.

METHODS
The 2005-2011 dental Global Health Professions Student Survey data were analysed for 13,040 third-year dental students from 43 countries. Knowledge about NRT was self-reported and country-specific prevalence estimates were calculated. To assess for correlates of knowledge about NRT amongst dental students, a multivariate logistic regression model was fitted (P < 0.05), with pooled data from all 43 countries. The model assessed for geographical location, gross national income, tobacco cessation training in school, sex, current tobacco use and survey year.

RESULTS
Amongst all dental students, the proportion that knew about NRT ranged from 37.0% (Mongolia) to 97.6% (Slovakia). The odds of knowing about NRT were lower amongst dental students in the Eastern Mediterranean region (aOR = 0.52; 95% CI: 0.34-0.79) compared to those in the European region. Dental students in upper-middle-income (aOR = 2.46; 95% CI: 1.57-3.85) and high-income countries (aOR=4.55; 95% CI: 2.28-9.09) both had higher odds of knowing about NRT compared to dental students in low-income countries. Also, current use of any tobacco product and receipt of tobacco cessation training in school were both associated with higher likelihood of knowing about NRT. No significant gender differences in knowledge of NRT were observed.

CONCLUSIONS
A large proportion of dental students in several countries knew about NRT. However, disparities in knowledge existed across regions. Enhanced efforts are needed to formally train dental students on tobacco cessation techniques.

D007722:Health Knowledge, Attitudes, Practice

students tobacco cessation counselling dentists education


Effects of lower extremity constraint-induced movement therapy on gait and balance of chronic hemiparetic patients after stroke: description of a study protocol for a randomized controlled clinical trial.

Abstract:
BACKGROUND
Protocols involving intensive practice have shown positive outcomes. Constraint induced movement therapy (CIT) appears to be one of the best options for better outcomes in upper limb rehabilitation, but we still have little data about lower extremity constraint-induced movement therapy (LE-CIT) and its effects on gait and balance.

OBJECTIVE
To evaluate the effects of an LE-CIT protocol on gait functionality and balance in chronic hemiparetic patients following a stroke.

METHODS
The study adopts a randomized, controlled, single-blinded study design. Forty-two patients, who suffered a stroke, who were in the chronic phase of recovery (>6 months), with gait disability (no community gait), and who were able to walk at least 10 m with or without the advice or support of 1 person, will be randomly allocated to 2 groups: the LE-CIT group or the control group (intensive conventional therapy). People will be excluded if they have speech deficits that render them unable to understand and/or answer properly to evaluation scales and exercises selected for the protocol and/or if they have suffered any clinical event between the screening and the beginning of the protocol. Outcome will be assessed at baseline (T0), immediately after the intervention (T1), and after 6 months (T2). The outcome measures chosen for this trial are as follows: 6-min walk test (6minWT), 10-m walk test (10mWT), timed up and go (TUG), 3-D gait analysis (3DGA), Mini Balance Evaluation Systems Test (Mini-BESTest), and as a secondary measure, Lower Extremity Motor Activity Log will be evaluated (LE-MAL). The participants in both groups will receive 15 consecutive days of daily exercise. The participants in the LE-CIT group will be submitted to this protocol 2.5 h/day for 15 consecutive days. It will include (1) intensive supervised training, (2) use of shaping as strategy for motor training, and (3) application of a transfer package (plus 30 min). The control group will receive conventional physiotherapy for 2.5 h/day over 15 consecutive days (the same period as the CIT intervention). Repeated measures analyses will be made to compare differences and define clinically relevant changes between groups.

RESULTS
Data collection is currently on-going and results are expected in 2021.

DISCUSSION
LE-CIT seems to be a good protocol for inclusion into stroke survivors' rehabilitation as it has all the components needed for positive results, as well as intensity and transference of gains to daily life activities.

TRIAL REGISTRATION
www.ensaiosclinicos.gov.br RBR-467cv6 . Registered on 10 October 2017. "Effects of Lower Extremities - Constraint Induced Therapy on gait and balance function in chronic hemipretic post-stroke patients".

D016032:Randomized Controlled Trials as Topic

Constraint-induced movement therapy
Gait
Balance
Stroke
Hemiparesis


Tackling tumor heterogeneity and phenotypic plasticity in cancer precision medicine: our experience and a literature review.

Abstract: The predominant cause of cancer mortality is metastasis. The major impediment to cancer cure is the intrinsic or acquired resistance to currently available therapies. Cancer is heterogeneous at the genetic, epigenetic, and metabolic levels. And, while a molecular-targeted drug may be pathway-precise, it can still fail to achieve wholesome cancer-precise toxicity. In the current review, we discuss the strategic differences between targeting the strengths of cancer cells in phenotypic plasticity and heterogeneity and targeting shared vulnerabilities of cancer cells such as the compromised integrity of membranous organelles. To better recapitulate subpopulations of cancer cells in different phenotypic and functional states, we developed a schematic combination of 2-dimensional culture (2D), 3-dimmensional culture in collagen I (3D), and mammosphere culture for stem cells (mammosphere), designated as Scheme 2D/3D/mammosphere. We investigated how the tumor suppressor maspin may limit carcinoma cell plasticity and affect their context-dependent response to drugs of different mechanisms including docetaxel, histone deacetylase (HDAC) inhibitor MS-275, and ionophore antibiotic salinomycin. We showed that tumor cell phenotypic plasticity is not an exclusive attribute to cancer stem cells. Nonetheless, three subpopulations of prostate cancer cells, enriched through Scheme 2D/3D/mammosphere, show qualitatively different drug responses. Interestingly, salinomycin was the only drug that effectively killed all three cancer cell subpopulations, irrespective of their capacity of stemness. Further, Scheme 2D/3D/mammosphere may be a useful model to accelerate the screening for curative cancer drugs while avoiding costly characterization of compounds that may have only selective toxicity to some, but not all, cancer cell subpopulations.

Sheng|Shijie|S|
Margarida Bernardo|M|M|
Dzinic|Sijana H|SH|
Chen|Kang|K|
Heath|Elisabeth I|EI|
Sakr|Wael A|WA|

D004354:Drug Screening Assays, Antitumor

Integrity of membranous subcellular structures


Prevalence, awareness, treatment, and control of hypertension among very elderly Chinese: results of a community-based study.

Abstract: The epidemiologic distribution of hypertension among very elderly Chinese is still not clear. This study aimed to investigate the prevalence, awareness, treatment, and control rate of hypertension among very elderly in Chengdu. From May 2013 to May 2015, a total of 1056 participants from 20 residential communities were sampled. Standard face-to-face interviews, physical examinations, and biochemical analysis were undertaken. Participants had a mean age of 83.6 ± 3.4 years (range: 80-100), and 49.8% were men. Mean systolic blood pressure (BP) and diastolic BP were 146.4 ± 20.6 and 74.1 ± 11.9 mm Hg, respectively, and both of the highest BP levels were among participants aged 80-84 years. Mean pulse pressure was 72.5 ± 17.1 mm Hg, and the highest pulse pressure level was among participants aged 90 years and older. The overall estimated hypertension prevalence was 75.3% (95% confidence interval: 72.6%-77.9%), and among overall participants, 51.9% were aware of their hypertensive condition and 45.5% were treated. However, only 18.1% of hypertensive participants were controlled (BP < 140/90 mm Hg). Among very elderly Chinese in Chengdu, the prevalence of hypertension is predominantly high, whereas awareness, treatment, and control rates are considerably low. Effective primary and secondary prevention strategies are needed.

Huang|Gang|G| Xu|Jun-Bo|JB| Zhang|Ting-Jie|TJ| Li|Qiu|Q| Nie|Xiao-Li|XL| Liu|Ya|Y| Peng|Shun-Rong|SR| Liu|Jian-Kang|JK| Liu|Xing-Tang|XT| Kang|Xiao-Ling|XL|

prevalence
hypertension
very elderly
Chinese


Accuracy of experimental mandibular osteotomy using the image-guided sagittal saw.

Abstract: The aim of this study was to perform an objective assessment of the accuracy of mandibular osteotomy simulations performed using an image-guided sagittal saw. A total of 16 image-guided mandibular osteotomies were performed on four prefabricated anatomical models according to the virtual plan. Postoperative computed tomography (CT) image data were fused with the preoperative CT scan allowing an objective comparison of the results of the osteotomy executed with the virtual plan. For each operation, the following parameters were analyzed and compared independently twice by two observers: resected bone volume, osteotomy trajectory angle, and marginal point positions. The mean target registration error was 0.95±0.19mm. For all osteotomies performed, the mean difference between the planned and actual bone resection volumes was 8.55±5.51%, the mean angular deviation between planned and actual osteotomy trajectory was 8.08±5.50°, and the mean difference between the preoperative and the postoperative marginal point positions was 2.63±1.27mm. In conclusion, despite the initial stages of the research, encouraging results were obtained. The current limitations of the navigated saw are discussed, as well as the improvements in technology that should increase its predictability and efficiency, making it a reliable method for improving the surgical outcomes of maxillofacial operations.

Pietruski|P|P| Majak|M|M| Swiatek-Najwer|E|E| Popek|M|M| Szram|D|D| Zuk|M|M| Jaworowski|J|J|

D006801:Humans
D021621:Imaging, Three-Dimensional
D008334:Mandible
D063168:Mandibular Osteotomy
D008953:Models, Anatomic
D010027:Osteotomy
D025321:Surgery, Computer-Assisted
D014057:Tomography, X-Ray Computed
D014584:User-Computer Interface

accuracy
computer-assisted surgery
image-guided surgery
intraoperative navigation
orthognathic surgery


Glycogen synthase kinase-3 overexpression replicates electroretinogram anomalies of offspring at high genetic risk for schizophrenia and bipolar disorder.

Abstract:
BACKGROUND
Electroretinogram (ERG) anomalies occur in patients with psychiatric disorders and represent potential biomarkers for diagnosis. For instance, decreased rod ERG (b-wave amplitude at Vmax) is a biological endophenotype in young offspring at high genetic risk (HR) for schizophrenia (SZ) and bipolar disorder (BD). Also, a decrease in cone a-wave and rod a- and b- wave was observed in SZ patients. However, the biological underpinning of these anomalies remains unknown. Several genetic variants associated with enhanced risk for SZ and/or BD can activate glycogen synthase kinase-3 isozymes (GSK3α and β). Here we examined the potential contribution of GSK3α and β in the modulation of the ERG.

METHODS
Cone and rod ERGs were recorded in mice having increased (prpGSK3β mice) or reduced (GSK3β(+/-) mice) GSK3β expression and in GSK3α knockout (KO) mice.

RESULTS
In prpGSK3β mice, we observed a decrease in rod b-wave amplitude at Vmax, whereas enhanced b-wave amplitude at Vmax was found in GSK3β(+/-) mice. An increase in cone a- and b-wave amplitude at Vmax and in rod b-wave amplitude at Vmax was observed in GSK3α-KO mice.

CONCLUSIONS
GSK3 expression modulates some ERG parameters. The phenotype observed in prpGSK3β mice is consistent with observations made in HRs. ERG anomalies observed in GSK3β(+/-) and GSK3α-KO mice confirm an association between the rod and cone b-wave amplitude and the expression of GSK3 isozymes. Changes in GSK3 expression or activity may explain some ERG anomalies in HRs and patients, thus supporting the biological validity of ERG measurements as a valuable biomarker for psychiatric research.

D020022:Genetic Predisposition to Disease

D000071679:Glycogen Synthase Kinase 3 beta

glycogen synthase kinase-3
electroretinogram
schizophrenia
bipolar disorder
Biomarker
risk factor


Gene Therapy for Glaucoma by Ciliary Body Aquaporin 1 Disruption Using CRISPR-Cas9.

Abstract: Glaucoma is a common cause of blindness, yet current therapeutic options are imperfect. Clinical trials have invariably shown that reduction in intraocular pressure (IOP) regardless of disease subtype prevents visual loss. Reducing ciliary body aqueous humor production can lower IOP, and the adeno-associated virus ShH10 serotype was identified as able to transduce mouse ciliary body epithelium following intravitreal injection. Using ShH10 to deliver a single vector CRISPR-Cas9 system disrupting Aquaporin 1 resulted in reduced IOP in treated eyes (10.4 ± 2.4 mmHg) compared with control (13.2 ± 2.0 mmHg) or non-injected eyes (13.1 ± 2.8 mmHg; p < 0.001; n = 12). Editing in the aquaporin 1 gene could be detected in ciliary body, and no off-target increases in corneal or retinal thickness were identified. In experimental mouse models of corticosteroid and microbead-induced ocular hypertension, IOP could be reduced to prevent ganglion cell loss (32 ± 4 /mm2) compared with untreated eyes (25 ± 5/mm2; p < 0.01). ShH10 could transduce human ciliary body from post-mortem donor eyes in ex vivo culture with indel formation detectable in the Aquaporin 1 locus. Clinical translation of this approach to patients with glaucoma may permit long-term reduction of IOP following a single injection.

Wu|Jiahui|J|
Bell|Oliver H|OH|
Copland|David A|DA|
Young|Alison|A|
Pooley|John R|JR|
Maswood|Ryea|R|
Evans|Rachel S|RS|
Khaw|Peng Tee|PT|
Ali|Robin R|RR|
Dick|Andrew D|AD|
Chu|Colin J|CJ|

Glaucoma
ciliary body
Aquaporin
CRISPR-Cas9
intraocular pressure
AAV
gene editing


A novel calibration method incorporating nonlinear optimization and ball-bearing markers for cone-beam CT with a parameterized trajectory.

Abstract:
PURPOSE
Cone-beam (CB) CT is a powerful noninvasive imaging modality, and is widely used in many applications. Accurate geometric parameters are essential for high-quality image reconstruction. Usually, a CBCT system with higher spatial resolution, particularly on the order of microns or nanometers, will be more sensitive to the parametric accuracy. Here, we propose a novel calibration method combining a simple phantom containing ball bearing markers and an advanced optimization procedure. This method can be applied to CBCT with reproducible geometry and frame-to-frame invariant geometric parameters.

METHODS
Our proposed simplex-simulated annealing procedure minimizes the cost function that associates the geometrical parameters with the degree to which the back projections of the ball bearings in projections from various viewing angles converge, and the global minimum of the cost function corresponds to the actual geometric parameters. Specifically, six geometric parameters can be directly obtained by minimizing the cost function, and the last parameter, the distance from source to rotation axis (SRD), can be obtained using prior knowledge of the phantom - the spacing between the two ball bearings.

RESULTS
Numerical simulation was performed to validate that the proposed method with various noise levels. With the proposed method, the mean errors and standard deviations can be reduced to ∼10% and less than 1/3 of a competing benchmark method in the case of strong Gaussian noise (sigma = 200% of the pixel size) and large tilt angle (tilt angle =   ). The calibration experiments with micro-CT and high-resolution CT scanners demonstrate that the proposed method recovers imaging parameters accurately, leading to superior image quality.

CONCLUSION
The proposed method can obtain accurate geometric parameters of a CBCT system with a circular trajectory. While in the case of micro-CT the proposed method has a performance comparable to the competing method, for high-resolution CT, which is more sensitive to geometric calibration, the proposed method demonstrates higher calibration accuracy and more robustness than the benchmark algorithm.

Li|Guang|G| Luo|Shouhua|S| You|Chenyu|C| Getzin|Matthew|M| Zheng|Liang|L| Wang|Ge|G| Gu|Ning|N|

optimization
cone-beam CT
geometric calibration


Nitrate and Nitrogen Oxides: Sources, Health Effects and Their Remediation.

Abstract: Increased use of nitrogenous (N) fertilizers in agriculture has significantly altered the global N-cycle because they release nitrogenous gases of environmental concerns. The emission of nitrous oxide (N2O) contributes to the global greenhouse gas accumulation and the stratospheric ozone depletion. In addition, it causes nitrate leaching problem deteriorating ground water quality. The nitrate toxicity has been reported in a number of studies showing the health hazards like methemoglobinemia in infants and is a potent cause of cancer. Despite these evident negative environmental as well as health impacts, consumption of N fertilizer cannot be reduced in view of the food security for the teeming growing world population. Various agronomic and genetic modifications have been practiced to tackle this problem. Some agronomic techniques adopted include split application of N, use of slow-release fertilizers, nitrification inhibitors and encouraging the use of organic manure over chemical fertilizers. As a matter of fact, the use of chemical means to remediate nitrate from the environment is very difficult and costly. Particularly, removal of nitrate from water is difficult task because it is chemically non-reactive in dilute aqueous solutions. Hence, the use of biological means for nitrate remediation offers a promising strategy to minimize the ill effects of nitrates and nitrites. One of the important goals to reduce N-fertilizer application can be effectively achieved by choosing N-efficient genotypes. This will ensure the optimum uptake of applied N in a balanced manner and exploring the molecular mechanisms for their uptake as well as metabolism in assimilatory pathways. The objectives of this paper are to evaluate the interrelations which exist in the terrestrial ecosystems between the plant type and characteristics of nutrient uptake and analyze the global consumption and demand for fertilizer nitrogen in relation to cereal production, evaluate the various methods used to determine nitrogen use efficincy (NUE), determine NUE for the major cereals grown across large agroclimatic regions, determine the key factors that control NUE, and finally analyze various strategies available to improve the use efficiency of fertilizer nitrogen.

Hakeem|Khalid Rehman|KR|
Sabir|Muhammad|M|
Ozturk|Munir|M|
Akhtar|Mohd Sayeed|MS|
Ibrahim|Faridah Hanum|FH|

D052918:Environmental Restoration and Remediation

Nitrogen oxides
Nitrous oxide
Ozone depletion
Nitrate toxicity
Methemoglobinemia
Slow-release fertilizers
Environment
N-efficient genotypes
Environmental pollution
Fertilizer use efficiency
Global climate change
Global warming
Glutamine synthase
Nitrate assimilation
Nitrate pollution
Nitrate reductase
Nitrate uptake
Nitrite reductase
Nitrogen emission
Nitrogen metabolism pathway
Nitrogen use efficiency
Nitrosamines
Phytoremediation
Transcription factors
Transgenic plants

P P P P P P P P M R M M U M M M R M R R R U U M M


Valorization of biodiesel side stream waste glycerol for rhamnolipids production by Pseudomonas aeruginosa RS6.

Abstract: Biodiesel side stream waste glycerol was identified as a cheap carbon source for rhamnolipids (RLs) production which at the same time could improve the management of waste. The present study aimed to produce RLs by using Pseudomonas aeruginosa RS6 utilizing waste glycerol as a substrate and to evaluate their physico-chemicals properties. Fermentation conditions such as temperature, initial medium pH, waste glycerol concentration, nitrogen sources and concentrations resulted in different compositions of the mono- and di-RLs produced. The maximum RLs production of 2.73 g/L was obtained when P. aeruginosa RS6 was grown in a basal salt medium supplemented with 1% waste glycerol and 0.2 M sodium nitrate at 35 °C and pH 6.5. At optimal fermentation conditions, the emulsification index (E24) values of cooking oil, diesel oil, benzene, olive oil, petroleum, and kerosene were all above E24=50%. The surface tension reduction obtained from 72.13 mN/m to 29.4-30.4 mN/m was better than the surface activity of some chemical-based surfactants. The RLs produced possessed antimicrobial activities against Gram-negative and Gram-positive bacteria with values ranging from 37% to 77% of growth inhibition when 1 mg/mL of RLs was used. Concentrations of RLs below 1500 μg/mL did not induce phytotoxicity effects on the tested seeds (Vigna radiata) compared to the chemical-based- surfactant, SDS. Furthermore, RLs tested on zebrafish (Danio rerio) embryos only exhibited low acute toxicity with an LC50 value of 72.97 μg/mL at 48 h of exposure suggesting a green and eco-biochemical worthy of future applications to replace chemical-based surfactants.

Baskaran|Shobanah Menon|SM|
Zakaria|Mohd Rafein|MR|
Mukhlis Ahmad Sabri|Ahmad Syafiq|AS|
Mohamed|Mohd Shamzi|MS|
Wasoh|Helmi|H|
Toshinari|Maeda|M|
Hassan|Mohd Ali|MA|
Banat|Ibrahim M|IM|

Valorization
Waste glycerol
Rhamnolipid
Green chemicals
P. aeruginosa, eco-biomaterial


A novel mutation in the leptin gene (W121X) in an Egyptian family.

Abstract: Congenital leptin deficiency is a rare recessively inherited condition due to homozygous mutations in the LEP gene. To date, only nine mutations have been identified in the LEP gene (p.L72S, p.N103K, p.R105W, p.H118L, p.S141C, c.104_106delTCA, c.135del3bp, c.398delG and c.481_482delCT). In this study we present a novel homozygous nonsense mutation (W121X) in LEP in a twelve year old obese male and his severely obese sister. As this disorder is treatable with recombinant leptin, it is intriguing to report a novel homozygous nonsense mutation in LEP in two obese children of consanguineous parents. These patients showed features in accordance with leptin deficiency.

Mazen|Inas|I|
Amr|Khalda|K|
Tantawy|Sally|S|
Farooqi|I Sadaf|IS|
El Gammal|Mona|M|


Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection.

Abstract: Johne's disease or paratuberculosis is a chronic debilitating disease in ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). The disease causes significant economic losses in livestock industries worldwide. There are no effective control measures to eradicate the disease because there are no appropriate diagnostic methods to detect subclinically infected animals. Therefore, it is very difficult to control the disease using only test and cull strategies. Vaccination against paratuberculosis has been considered as an alternative strategy to control the disease when combined with management interventions. Understanding host-pathogen interactions is extremely important to development of vaccines. It has long been known that Th1-mediated cellular immune responses are play a crucial role in protection against MAP infection. However, recent studies suggested that innate immune responses are more closely related to protective effects than adaptive immunity. Based on this understanding, several attempts have been made to develop vaccines against paratuberculosis. A variety of ideas for designing novel vaccines have emerged, and the tests of the efficacy of these vaccines are conducted constantly. However, no effective vaccines are commercially available. In this study, studies of the development of vaccines for MAP were reviewed and summarized.


Photo-induced toxicity of titanium dioxide nanoparticles to Daphnia magna under natural sunlight.

Abstract: Titanium dioxide nanoparticles (TiO2 NP) are one of the most abundantly utilized nanoparticles in the world. Studies have demonstrated the ability of the anatase crystal of TiO2 NP to produce reactive oxygen species (ROS) in the presence of ultraviolet radiation (UVR), a co-exposure likely to occur in aquatic ecosystems. The goal of this study was to examine the photo-induced toxicity of anatase TiO2 NP under natural sunlight to Daphnia magna. D. magna were exposed to a range of UVR intensities and anatase TiO2 concentrations in an outdoor exposure system using the sun as the source of UVR. Different UVR intensities were achieved using UVR opaque and transparent plastics. AnataseTiO2-NP demonstrated the reciprocal relationship seen in other phototoxic compounds such as polycyclic aromatic hydrocarbons (PAHs) at higher UVR treatments. The calculated 8h LC50 of anatase TiO2 NP was 139 ppb under full intensity ambient natural sunlight, 778 ppb under 50% natural sunlight, and >500 ppm under 10% natural sunlight. Mortality was also compared between animals allowed to accumulate a body burden of anatase TiO2 for 1h and organisms whose first exposure to anatase TiO2 aqueous suspensions occurred under UVR. A significantly greater toxic effect was observed in aqueous, low body burden suspensions than that of TiO2 1h body burdens, which is dissimilar from the model presented in PAHs. Anatase TiO2 presents a unique photo-induced toxic model that is different than that of established phototoxic compounds.

Mansfield|C M|CM|
Alloy|M M|MM|
Hamilton|J|J|
Verbeck|G F|GF|
Newton|K|K|
Klaine|S J|SJ|
Roberts|A P|AP|

Photo-induced toxicity
Titanium dioxide
Nanoparticles
Ultraviolet radiation


Revegetation of the riparian zone of the Three Gorges Dam Reservoir leads to increased soil bacterial diversity.

Abstract: As one of the most active components in soil, bacteria can affect soil physicochemical properties, its biological characteristics, and even its quality and health. We characterized dynamics of the soil bacterial diversity in planted (with Taxodium distichum) and unplanted soil in the riparian zone of the Three Gorges Dam Reservoir (TGDR), in southwestern China, in order to accurately quantify the changes in long-term soil bacterial community structure after revegetation. Measurements were taken annually in situ in the TGDR over the course of 5 years, from 2012 to 2016. Soil chemical properties and bacterial diversity were analyzed in both the planted and unplanted soil. After revegetation, the soil chemical properties in planted soil were significantly different than in unplanted soil. The effects of treatment, time, and the interaction of both time and treatment had significant impacts on most diversity indices. Specifically, the bacterial community diversity indices in planted soil were significantly higher and more stable than that in unplanted soil. The correlation analyses indicated that the diversity indices correlated with the pH value, organic matter, and soil available nutrients. After revegetation in the riparian zone of the TGDR, the soil quality and health is closely related to the observed bacterial diversity, and a higher bacterial diversity avails the maintenance of soil functionality. Thus, more reforestation should be carried out in the riparian zone of the TGDR, so as to effectively mitigate the negative ecological impacts of the dam. Vegetating the reservoir banks with Taxodium distichum proved successful, but planting mixed stands of native tree species could promote even higher riparian soil biodiversity and improved levels of ecosystem functioning within the TGDR.

Ren|Qingshui|Q|
Li|Changxiao|C|
Yang|Wenhang|W|
Song|Hong|H|
Ma|Peng|P|
Wang|Chaoying|C|
Schneider|Rebecca L|RL|
Morreale|Stephen J|SJ|

D003247:Conservation of Natural Resources

Revegetation
Bacterial diversity
Taxodium distichum
Hydro-fluctuation zone
T-RFLP
The Three Gorges Reservoir Region


Which probiotic has the best effect on preventing Clostridium difficile-associated diarrhea? A systematic review and network meta-analysis.

Abstract:
OBJECTIVE
Clostridium difficile-associated diarrhea (CDAD) accounts for up to 25% of patients with antibiotic-associated diarrhea (AAD). We aimed to determine which probiotic is most effective in preventing CDAD using a network meta-analysis.

METHODS
Studies were identified by searching PubMed, EMBASE and the Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the efficacy of probiotic interventions for CDAD. Primary outcomes were the incidence rates of AAD and CDAD, and secondary outcomes were the duration of diarrhea and the time until onset of diarrhea. The PROSPERO registered number of this study is CRD42018106115.

RESULTS
Ten RCTs including 11 analyses and including 4 692 patients were identified. Compared with the control group, probiotic intervention reduced the incidence rates of CDAD (odds ratio [OR] 0.33, 95% confidence interval [CI] 0.17-0.61) and AAD (OR 0.39, 95% CI 0.23-0.66). Similar results were observed regarding the duration of diarrhea and the time until onset of diarrhea. Meta-regression analysis showed a correlation between the type of probiotic used and the incidence of CDAD and AAD. All nine kinds of probiotic interventions were statistically more effective than the placebo, with Lactobacillus casei ranking as the best intervention (OR 0.19, 95% credible interval [CrI] 0.06-0.63) for decreasing the incidence rate of CDAD. L. casei also ranked the highest in reducing the incidence rate of AAD (OR 0.32, 95% CrI 0.14-0.74).

CONCLUSION
Lactobacilli strains, especially L. casei, have a good effect on the prevention of CDAD and AAD.

probiotics
prevention
network meta-analysis
antibiotic-associated diarrhea
Clostridium difficile


Targeted Drug Delivery Technologies Potentiate the Overall Therapeutic Efficacy of an Indole Derivative in a Mouse Cystic Fibrosis Setting.

Abstract: Inflammation plays a major role in the pathophysiology of cystic fibrosis (CF), a multisystem disease. Anti-inflammatory therapies are, therefore, of interest in CF, provided that the inhibition of inflammation does not compromise the ability to fight pathogens. Here, we assess whether indole-3-aldehyde (3-IAld), a ligand of the aryl hydrocarbon receptor (AhR), may encompass such an activity. We resorted to biopharmaceutical technologies in order to deliver 3-IAld directly into the lung, via dry powder inhalation, or into the gut, via enteric microparticles, in murine models of CF infection and inflammation. We found the site-specific delivery of 3-IAld to be an efficient strategy to restore immune and microbial homeostasis in CF organs, and mitigate lung and gut inflammatory pathology in response to fungal infections, in the relative absence of local and systemic inflammatory toxicity. Thus, enhanced delivery to target organs of AhR agonists, such as 3-IAld, may pave the way for the development of safe and effective anti-inflammatory agents in CF.

D019005:Cystic Fibrosis Transmembrane Conductance Regulator

drug delivery
cystic fibrosis
inflammation
3-IAld
aryl hydrocarbon receptor


Development of Neutral pH-Responsive Microgels by Tuning Cross-Linking Conditions.

Abstract: Polymer microgels that respond in a range of neutral pH can be useful for the development of molecular imaging tools and drug-delivery carriers. Here, we describe a simple approach in developing microgels that undergo volume phase transitions and substantial nuclear magnetic resonance (NMR) relaxometric changes within a narrow pH range of 6.4 to 7.4. The pH-responsive microgels were synthesized using methacrylic acid and a series of ethylene glycol dimethacrylate cross-linkers with repeating units of ethylene glycol that range from one to four. NMR relaxometry demonstrated that the transverse relaxation time (T2) of a suspension containing microgels that were cross-linked with diethylene glycol dimethacrylate sharply decreases at the pH where volume phase transition occurs. The polymer microgels cross-linked with 40 and 45 mol% of diethylene glycol dimethacrylate caused about 50% T2 reduction with decreasing pH from 6.8 to 6.4. These results demonstrated that responses of microgels to a range of neutral pH can be easily tuned by using appropriate cross-linkers with certain cross-linking degree. This approach can be useful in developing highly sensitive molecular sensors for magnetic resonance imaging (MRI) of tissue pH values.

D005026:Ethylene Glycols
D006863:Hydrogen-Ion Concentration
D000080386:Microgels
D011109:Polymethacrylic Acids

pH-responsive microgels
volume phase transition
MRI
NMR relaxation time


Ghrelin exhibited antidepressant and anxiolytic effect via the p38-MAPK signaling pathway in hippocampus.

Abstract: Ghrelin, a peptide derived from stomach, is an endogenous ligand for growth hormone secretagogue receptor (GHSR). So far, the exact role of ghrelin in depression and anxiety is still being debated. The p38 mitogen-activated protein kinase (p38-MAPK) is known to be activated in response to various stress stimuli. Thus, we hypothesize that ghrelin has an antidepressant effect, to which the p38-MAPK signaling pathway significantly contributes. To test this hypothesis, chronic social defeat stress (CSDS) was used as a model of depression. We employed the adeno-associated virus-mediated siRNA approach to down-regulate GHSR expression in the hippocampus of mice in vivo. Both ghrelin and the p38 inhibitor, SB203580, were administered to identify the effect of ghrelin on depressive-like behavior of stressed mice and to better assess the role of the p38-MAPK signaling pathway in this process. We found that CSDS activated the endogenous ghrelin-GHSR in hippocampal neurons, which possibly resulted in opposing the formation of depression- and anxiety-like behaviors in mice. Furthermore, the p38-MAPK signaling pathway had an important role in the antidepressant effect of ghrelin. Therefore, we conclude that ghrelin may reduce CSDS-induced depression- and anxiety-like behaviors via inhibiting the p38-MAPK signaling pathway in hippocampal neurons of mice.

Han|Qiu-Qin|QQ| Huang|Hui-Jie|HJ| Wang|Ya-Lin|YL| Yang|Liu|L| Pilot|Adam|A| Zhu|Xiao-Cang|XC| Yu|Rui|R| Wang|Jing|J| Chen|Xiao-Rong|XR| Liu|Qiong|Q| Li|Bing|B| Wu|Gen-Cheng|GC| Yu|Jin|J|

Ghrelin
Depression
P38
Chronic social defeat stress (CSDS)


How to set up a standard regional anesthesia service?

Abstract: The practice of regional anesthesia is getting more popular after the introduction of ultrasound technology in anesthesia practice. The biggest obstacle in conducting regional anesthesia is the delay in operation room time. This brief report focuses on the set up of the so called "block room".

regional anesthesia
Block room
quality management


Flotation/ultrasound-assisted microextraction followed by HPLC for determination of fat-soluble vitamins in multivitamin pharmaceutical preparations.

Abstract: Dissolved carbon dioxide flotation-emulsification microextraction technique coupled with high-performance liquid chromatography was developed for separation and determination of fat-soluble vitamins (A, D3 , E, and K3 ) in multivitamin pharmaceutical preparations. Dissolved carbon dioxide flotation was used to break up the emulsion of extraction solvent in water and to collect the extraction solvent on the surface of aqueous sample in narrowed capillary part of extraction cell. Carbon dioxide bubbles were generated in situ through the addition of 300 μL of concentrated hydrochloric acid into the alkaline sample solution at pH = 11.5 (1% w/v sodium carbonate), which was sonicated to intensify the carbon dioxide bubble generation. Several factors affecting the extraction process were optimized. Under the optimal conditions, the limits of detection were 0.11, 0.47, 0.20 and 0.35 μg/L for A, E, D3 , and K3 vitamins in water samples, respectively. The inter-day and intra-day precision of the proposed method were evaluated in terms of the relative standard deviation and were <10.5%.

D002851:Chromatography, High Pressure Liquid

microextraction
fat-soluble vitamins
high-performance liquid chromatography
dissolved carbon dioxide flotation
multivitamin analysis


International transfers of health data between the EU and USA: a sector-specific approach for the USA to ensure an 'adequate' level of protection.

Abstract: International health research increasingly depends on collaboration and combination using medical data to advance treatment and drug discovery. The European Union (EU), through its General Data Protection Regulation, has tightened the rules for sharing data across borders to protect individual privacy. These new rules threaten cooperation between the EU and the USA, the two largest public funders of biomedical research. This article analyzes the primary pathway for sharing research data with the USA, the US-EU Privacy Shield, and argues that the Shield is ill-suited to support complex health studies. Its legitimacy is in question under both EU and US law, and its terms are too restrictive for the variety of exchanges underlying research, treatment, and care. As an alternative, we propose that the USA seek an additional sector-based adequacy determination based on the existing US health privacy law, the Health Insurance Portability and Accountability Act. A sector-specific approach to adequacy for health would avoid many of the most contentious issues that divide the USA and EU on data protection. It could also serve as a model for other third-party jurisdictions and facilitate international harmonization of health research practices.

EU–US privacy shield
GDPR
HIPAA
cross-border transfers
privacy and data protection


Rational Design and Synthesis of Naphthalene Diimide Linked Bis-Naphthalimides as DNA Interactive Agents.

Abstract: A molecular modeling assisted rational design and synthesis of naphthalene diimide linked bis-naphthalimides as potential DNA interactive agents is described. Chemical templates incorporating naphthalene diimide as a linker in bis-naphthalimide motif were subjected to molecular docking analysis at specific intercalation and telomeric DNA G-quadruplex sites. Excellent results were obtained, which were better than the standards. A short and convenient synthetic route was employed to access these hybrids experimentally, followed by evaluation of their ability to cause thermal denaturation of DNA and cytotoxic properties along with ADME predictions. The obtained results provided useful insights and two potential molecules were identified for further development.

Malik|M Shaheer|MS|
Farooq Adil|Syed|S|
Moussa|Ziad|Z|
Altass|Hatem M|HM|
Althagafi|Ismail I|II|
Morad|Moataz|M|
Ansari|Mohammad Azam|MA|
Sajid Jamal|Qazi Mohammad|QM|
Obaid|Rami J|RJ|
Al-Warthan|Abdulrahman A|AA|
Shaik|Thokhir B|TB|
Ahmed|Saleh A|SA|

naphthalene diimide
bis-naphthalimides
DNA interactive
molecular modeling
anticancer agents


Cloning of the promoter of NDE1, a gene implicated in psychiatric and neurodevelopmental disorders through copy number variation.

Abstract: Copy number variation at 16p13.11 has been associated with a range of neurodevelopmental and psychiatric conditions, with duplication of this region being more common in individuals with schizophrenia. A prominent candidate gene within this locus is NDE1 (Nuclear Distribution Element 1) given its known importance for neurodevelopment, previous associations with mental illness and its well characterized interaction with the Disrupted in Schizophrenia 1 (DISC1) protein. In order to accurately model the effect of NDE1 duplication, it is important to first gain an understanding of how the gene is expressed. The complex promoter system of NDE1, which produces three distinct transcripts, each encoding for the same full-length NDE1 protein (also known as NudE), was therefore cloned and tested in human cell lines. The promoter for the longest of these three NDE1 transcripts was found to be responsible for the majority of expression in these systems, with its extended 5' untranslated region (UTR) having a limiting effect on its expression. These results thus highlight and clone the promoter elements required to generate systems in which the NDE1 protein is exogenously expressed under its native promoter, providing a biologically relevant model of 16p13.11 duplication in major mental illness.

D017398:Alternative Splicing
D001483:Base Sequence
D045744:Cell Line, Tumor
D003001:Cloning, Molecular
D056915:DNA Copy Number Variations
D057809:HEK293 Cells
D006801:Humans
D008869:Microtubule-Associated Proteins
D011401:Promoter Regions, Genetic

schizophrenia
Nuclear Distribution Element 1 (NDE1)
alternate splicing
chromosome 16p13.11 duplication
copy number variation (CNV)
promoter characterization


6-Substituted 9-fluoroquino[3,2-b]benzo[1,4]thiazines display strong antiproliferative and antitumor properties.

Abstract: 6-Substituted 9-fluoroquino[3,2-b]benzo[1,4]thiazines - a new type of tetracyclic azaphenothiazines-were obtained from of 6H-9-fluoroquinobenzothiazine by the introduction of appropriate substituents to the thiazine nitrogen atom (alkyl, aminoalkyl, amidoalkyl, sulfonamidoalkyl and nitrogen half-mustard groups). The compounds displayed differential cytotoxic as well as antiproliferative actions against human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin A (PHA). In addition, they suppressed lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-α) production by whole blood human cell cultures. Two compounds (4 and 15, with the propargyl and methanesulfonamidopropyl groups) were selected for further experiments because of lack of cytotoxicity and strong antiproliferative actions. Compound 4 showed strong suppressive actions on growth of L1210, SW948, A-431 and CX-1 tumor cell lines which were close to those of cisplatin, the reference drug (e.g. GI50 of 2.28 μg/mL vs. 1.86 μg/mL for L1210 cells). Further, the compound appeared to be equally effective as cyclosporine A (CsA) in the inhibition of human two-way mixed lymphocyte reaction (MLR). The compound did not significantly inhibit interleukin 2 (IL-2)-induced growth of CTLL-2 cell line. In addition, inhibition of prostaglandin (PG) synthesis by indomethacin or block of PG receptors did not interfere with the inhibitory effect of the compound on PHA-induced cell proliferation. Therefore, it is likely that the compound acts by inhibiting cell cycle as proposed for other phenothiazines. Further studies are required for the elucidation of the mechanism of action and therapeutic utility of these compounds in more advanced in vivo models.

Jeleń|Małgorzata|M| Pluta|Krystian|K| Zimecki|Michał|M| Morak-Młodawska|Beata|B| Artym|Jolanta|J| Kocięba|Maja|M|

D000818:Animals
D000970:Antineoplastic Agents
D002453:Cell Cycle
D045744:Cell Line, Tumor
D049109:Cell Proliferation
D002470:Cell Survival
D015195:Drug Design
D024841:Fluoroquinolones
D006801:Humans
D007963:Leukocytes, Mononuclear
D015394:Molecular Structure
D010640:Phenothiazines
D013329:Structure-Activity Relationship
D014409:Tumor Necrosis Factor-alpha

Phenothiazines
Anticancer activity
Antiproliferative activity
Azaphenothiazines
Thiazine ring formation


Catalytic Carbonylation and Carboxylation of Organosulfur Compounds via C-S Cleavage.

Abstract: Transition-metal-catalyzed carbonylation with CO gas occupies a privileged position in organic synthesis for the synthesis of carbonyl compounds. Although this attractive and useful chemistry has led many researchers to investigate carbonylative transformations of various organic (pseudo)halides, C-S-cleaving carbonylation of organosulfur compounds has been fairly limited. Recently, a broad spectrum of C-S-cleaving transformations has been emerging in the field of cross-coupling. In light of the importance of carbonyl compounds as well as considerable advancement for employing organosulfur compounds as competent surrogates of (pseudo)halides, carbonylative transformations of C-S bonds should be of high value. This Minireview focuses on catalytic C-S carbonylation of organosulfur compounds with CO or its equivalents. In addition, reductive carboxylation of C-S bonds with CO2 is described.

Carbonylation
Carboxylation
Organosulfur compounds
C−S cleavage


Genomics Characterization of an Engineered Corynebacterium glutamicum in Bioreactor Cultivation Under Ionic Liquid Stress.

Abstract: Corynebacterium glutamicum is an ideal microbial chassis for production of valuable bioproducts including amino acids and next generation biofuels. Here we resequence engineered isopentenol (IP) producing C. glutamicum BRC-JBEI 1.1.2 strain and assess differential transcriptional profiles using RNA sequencing under industrially relevant conditions including scale transition and compare the presence vs absence of an ionic liquid, cholinium lysinate ([Ch][Lys]). Analysis of the scale transition from shake flask to bioreactor with transcriptomics identified a distinct pattern of metabolic and regulatory responses needed for growth in this industrial format. These differential changes in gene expression corroborate altered accumulation of organic acids and bioproducts, including succinate, acetate, and acetoin that occur when cells are grown in the presence of 50 mM [Ch][Lys] in the stirred-tank reactor. This new genome assembly and differential expression analysis of cells grown in a stirred tank bioreactor clarify the cell response of an C. glutamicum strain engineered to produce IP.

Banerjee|Deepanwita|D|
Eng|Thomas|T|
Sasaki|Yusuke|Y|
Srinivasan|Aparajitha|A|
Oka|Asun|A|
Herbert|Robin A|RA|
Trinh|Jessica|J|
Singan|Vasanth R|VR|
Sun|Ning|N|
Putnam|Dan|D|
Scown|Corinne D|CD|
Simmons|Blake|B|
Mukhopadhyay|Aindrila|A|

Corynebacterium glutamicum
bioreactor
ionic Liquid
isopentenol
acetoin
RNAseq
fed-batch
lignin hydrolysate


Rituximab induced cytokine release syndrome in an MS patient: A case report.

Abstract: Cytokine release syndrome with rituximab has been reported in certain diseases, however, it is rarely reported in MS patients treated with rituximab. The treating physician should suspect the syndrome when typical signs and symptoms appear.

rituximab
cytokine release syndrome
multiple sclerosis


Morphological features of the mandible as predictors for neurosensory disturbances after bilateral sagittal split osteotomy.

Abstract: This retrospective study aimed to identify anatomical predictors of neurosensory disturbance (NSD) after bilateral sagittal split ramus osteotomy (BSSO) by evaluating the morphology of the mandible on lateral cephalograms (LCs) and orthopantomograms (OPTs). The LCs and OPTs of 142 patients who underwent BSSO were reviewed. The influence of the mandibular angle was assessed on LCs, while the following morphological landmarks and subsequent measurements were analysed on OPTs: vertical and horizontal positions of the lingula, ramus width, mandibular body height, mandibular canal position and mandibular angle length. Post-operative NSD (hypoaesthesia) was considered permanent when objective tests or subjective evaluations indicated altered sensation one year after BSSO. Generalised linear mixed models were used to take into account the repeated measurement design (left and right measurements within one patient). Hypoaesthesia was present in 10.6% of the patients (5.6% of sites). After adjusting for age, a small mandibular body height was found to significantly increase the risk of hypoaesthesia. The other measurements showed no significant association with hypoaesthesia. These findings show a relationship between mandibular morphology and hypoaesthesia after BSSO and can aid surgeons in pre-operative assessments of the risk of NSD. Further research is needed to identify risk factors for NSD based on mandibular morphology.

Verweij|Jop P|JP|
Mensink|Gertjan|G|
Fiocco|Marta|M|
van Merkesteyn|J P Richard|JP|

Sagittal split osteotomy
Orthopantomogram
Hypoaesthesia
Mandibular morphology
Inferior alveolar nerve
Orthognathic surgery


Physical activity and sedentary behavior thresholds for identifying childhood hypertension and its phenotypes: The Healthy Growth Study.

Abstract: Hypertension phenotypes may represent differential pathophysiologic mechanisms and clinical impact, yet they have been poorly investigated. The study aimed to examine the associations of physical activity and sedentary behavior with hypertension phenotypes in a large group of Greek children and to identify thresholds regarding risk of hypertension. This was a cross-sectional study with a regionally representative sample of 2473 schoolchildren aged 9-13 years, with full data on physical activity and sedentary behavior indices, as well as arterial blood pressure measurements, physical examination, and anthropometry. Hypertensive children of both sexes had lower levels of physical activity (steps/d). Hypertensive girls had lower moderate-to-vigorous physical activity (MVPA), whereas hypertensive boys with isolated systolic hypertension (ISH) had more screen time than their normotensive counterparts. Increased levels of physical activity was associated with 33%-54% lower risk of all hypertension phenotypes in both sexes, whereas increased MVPA was associated with 41%-65% lower risk of all phenotypes in girls and with ISH and systolic and diastolic hypertension (SDH) in boys. In boys, higher sedentary time was associated with 11%-13% higher risk for SDH and ISH. Cutoff points of 12,378 steps/d, 47.3 min/d of MVPA, and 2.9 h/d of sedentary behavior were determined for identifying children at increased risk of hypertension. Physical activity is inversely associated with all hypertension phenotypes, whereas sedentary behavior is positively associated with ISH and SDH in boys. More studies should confirm the hypertension-specific cutoff values identified to be used in future prevention programs for childhood hypertension.

Karatzi|Kalliopi|K|
Moschonis|George|G|
Botelli|Sofia|S|
Androutsos|Odysseas|O|
Chrousos|George P|GP|
Lionis|Christos|C|
Manios|Yannis|Y|

physical activity
sedentary behavior
Childhood hypertension
hypertension phenotypes


Use of a smartphone thermometer to monitor thermal conductivity changes in diabetic foot ulcers: a pilot study.

Abstract:
OBJECTIVE
To investigate the dependability of a thermal gadget connecting to a smartphone. Comparing the exact temperature of damaged tissue with adjacent parts of the limb and to evaluate the changes in thermal conductivity of hard-to-heal wounds in patients with a diabetic foot ulcer (DFU).

METHODS
Potential candidates were divided into three groups and selected from different hospitals in Tehran. Group 1 contained patients with inflammation, Group 2 were patients with vascular complications, and Group 3 were patients who were managing to control their glucose levels to an acceptable level, according to their medical records (i.e. 'healthy cases'). All thermal images were taken without any external stimulus, in room temperature conditions after 15 minutes' rest. All medical records were confirmed by therapeutic supervisors. Moreover, the tissue conditions in patients were considered in the computational part of the study. The temperatures of the ulcer and adjacent tissues were observed and compared. The collected data were used in a suggested model for human tissues and the method of calculation in this study was trial and error. In this study, patients in Group 2 were considered in the computational section of the study.

RESULTS
Temperature difference between the wounds and adjacent tissues for the big toe in three patients in Group 2 was 2.2ºC for the healthier candidate and almost 6.9ºC in the worst case. By comparing the thermal conductivity of normal and damaged tissues, a significant reduction in thermal conductivity was observed for the candidate with the worst status of big toe by about 84.3%. For the other two candidates in this category, it was almost 68.86% and 20.47%.

CONCLUSION
The variation in thermal conductivity represents the change in tissue properties. Thermal conductivity can be applied for early DFU detection. This data may allow introduction of the smartphone thermometer as an authentic and alternative apparatus that is beneficial in diabetic clinics as well as self-assessment by patients. Moreover, due to the decrease in thermal conductivity, this study suggests using intelligent thermal sheets in vulnerable parts of the diabetic foot.

smartphone thermometer
thermal conductivity
diabetic foot ulcer
temperature
chronic wound


Volume changes of biochar-amended landfill cover soil under a thermal cycle.

Abstract: Biochar has been identified as a favourable amendment for landfill cover soils. So far, the effects of biochar on soil response to temperature variations are still unclear. Waste heat generates when municipal solid waste decomposes, and the temperature of landfill can increase up to 90°C. The present study aims to investigate the thermally induced volumetric behaviour of biochar-amended sand with different biochar application ratios of 0%, 5% and 10%. Experimental results show that, during heating from 23-83°C, pure sand expands. However, during the heating process biochar-amended sand samples contract first and then expand. This is because biochar treatment not only decreases soil density, but also promotes the formation of big size macro-aggregations with more macro-pores, which may be destroyed when particle rearrangements induced by thermal expansion occur. During the cooling process from 83-23°C, all the specimens with three biochar application ratios show contraction. Moreover, with an increasing biochar application ratio, the thermal expansion coefficient of the soil specimen decreases. This is because biochar is insensitive to temperature variation as it is produced in very high temperature. Therefore, biochar-amended soil is a promising alternative landfill cover material for municipal solid waste landfill, and the effect of temperature effect on its volume change in landfill cover design is also essential to be considered.

Qing|Cheng|C| Haowen|Guo|G| Tugen|Feng|F| Yang|Lu|L|

volume change
landfill cover
Biochar
temperature
thermal expansion coefficient


A systematic review and meta-analysis of the diagnostic accuracy of MRI for suspected ACL and meniscal tears of the knee.

Abstract:
PURPOSE
To determine the diagnostic accuracy of magnetic resonance imaging (MRI) and ultrasound (US) in the diagnosis of anterior cruciate ligament (ACL), medial meniscus and lateral meniscus tears in people with suspected ACL and/or meniscal tears.

METHODS
MEDLINE, Web of Science and the Cochrane library were searched from inception to March 2014. All prospective studies of the diagnostic accuracy of MRI or US against arthroscopy as the reference standard were included in the systematic review. Studies with a retrospective design and those with evidence of verification bias were excluded. Methodological quality of included studies was assessed using the QUADAS-2 tool. A meta-analysis of studies evaluating MRI to calculate the pooled sensitivity and specificity for each target condition was performed using a bivariate model with random effects. Sub-group and sensitivity analysis were used to examine the effect of methodological and other study variables.

RESULTS
There were 14 studies included in the meta-analysis of the accuracy of MRI for ACL tears, 19 studies included for medial meniscal tears and 19 studies for lateral meniscal tears. The summary estimates of sensitivity and specificity of MRI were 87 % (95 % CI 77-94 %) and 93 % (95 % CI 91-96 %), respectively, for ACL tears; 89 % (95 % CI 83-94 %) and 88 % (95 % CI 82-93 %), respectively, for medial meniscal tears; and 78 % (95 % CI 66-87 %) and 95 % (95 % CI 91-97 %), respectively, for lateral meniscal tears. Magnetic field strength had no significant effect on accuracy. Most studies had a high or unclear risk of bias. There were an insufficient number of studies that evaluated US to perform a meta-analysis.

CONCLUSION
This study provides a systematic review and meta-analysis of diagnostic accuracy studies of MRI and applies strict exclusion criteria in relation to the risk of verification bias. The risk of bias in most studies is high or unclear in relation to the reference standard. Concerns regarding the applicability of patient selection are also present in most studies.

LEVEL OF EVIDENCE
III.

Phelan|Nigel|N|
Rowland|Patrick|P|
Galvin|Rose|R|
O'Byrne|John M|JM|

D000070598:Anterior Cruciate Ligament Injuries

Magnetic resonance imaging
Anterior cruciate ligament
Medial meniscus
Lateral meniscus
Diagnostic test accuracy
Ultrasonography


The behaviour of monazite from greenschist facies phyllites to anatectic gneisses: An example from the Chugach Metamorphic Complex, southern Alaska.

Abstract: Monazite is a common accessory mineral in various metamorphic and magmatic rocks, and is widely used for U-Pb geochronology. However, linking monazite U-Pb ages with the PT evolution of the rock is not always straightforward. We investigated the behaviour of monazite in a metasedimentary sequence ranging from greenschist facies phyllites into upper amphibolites facies anatectic gneisses, which is exposed in the Eocene Chugach Metamorphic Complex of southern Alaska. We investigated textures, chemical compositions and U-Pb dates of monazite grains in samples of differing bulk rock composition and metamorphic grade, with particular focus on the relationship between monazite and other REE-bearing minerals such as allanite and xenotime. In the greenschist facies phyllites, detrital and metamorphic allanite is present, whereas monazite is absent. In lower amphibolites facies schists (~ 550-650 °C and ≥ 3.4 kbar), small, medium-Y monazite is wide-spread (Mnz1), indicating monazite growth prior and/or simultaneous with growth of garnet and andalusite. In anatectic gneisses, new low-Y, high-Th monazite (Mnz2) crystallised from partial melts, and a third, high-Y, low-Th monazite generation (Mnz3) formed during initial cooling and garnet resorption. U-Pb SHRIMP analysis of the second and third monazite generations yields ages of ~ 55-50 Ma. Monazite became unstable and was overgrown by allanite and/or allanite/epidote/apatite coronas within retrograde muscovite- and/or chlorite-bearing shear zones. This study documents polyphase, complex monazite growth and dissolution during a single, relatively short-lived metamorphic cycle.

Gasser|Deta|D| Bruand|Emilie|E| Rubatto|Daniela|D| Stüwe|Kurt|K|

Monazite
Chugach Metamorphic Complex
Alaska
Allanite
SHRIMP U–Pb geochronology


Rational Design of Memory-Based Sensors: the Case of Molecular Calorimeters.

Abstract: Thermodynamic characterization is crucial for understanding molecular interactions. However, methodologies for measuring heat changes in small open systems are extremely limited. We document a new approach for designing molecular sensors, that function as calorimeters: sensors based on memory. To design a memory-based sensor, we take advantage of the unique kinetic properties of nucleic acid scaffolds. Particularly, we elaborate on the differences in folding and unfolding rates in nucleic acid quadruplexes. DNA-based i-motifs unfold fast in response to small heats but do not fold back when the system is equilibrated with surroundings. We translated this behavior into a molecular memory function that enables the measurement of heat changes in open environments. The new sensors are biocompatible, operate homogeneously, and measure small heats released over long time periods. As a proof-of-concept, we demonstrate how the molecular calorimeters report heat changes generated in water/propanol mixing and in ligand/protein binding.

sensors
nucleic acids
biosensors
calorimetry
molecular devices


Modified energy settings are mandatory to minimize oesophageal injury using the novel multipolar irrigated radiofrequency ablation catheter for pulmonary vein isolation.

Abstract:
AIMS
The multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ™) is a novel tool for pulmonary vein isolation (PVI). We investigated the incidence of thermal oesophageal injury (EI) using the nMARQ™ for PVI.

METHODS AND RESULTS
In the initial six patients (Group 1), RF was delivered at the posterior wall with a maximum duration of 60 s and a maximum power (maxP) of 20 W for unipolar ablation, and a maxP of 10 W for the bipolar ablation. In the latter 15 patients (Group 2), RF application was limited at the posterior wall to a maximum duration of 30 s and a maxP of 15 W for unipolar ablation a max P of 10 W for bipolar ablation. Oesophageal temperature monitoring was performed in all patients and ablation was terminated at a temperature rise >41°C. Endoscopy was carried out within 2 days post-ablation. Pulmonary vein isolation was performed during sinus rhythm and was successfully achieved in 83 of 84 PVs except the septal inferior vein in one patient. Charring was seen in 3 of 21 (14.3%) patients without any evidence of embolism. Phrenic nerve palsy occurred in one patient. Endoscopy revealed severe EI in 3 of 6 (50%) patients in Group 1 and in 1 of 15 patients (6.7%) in Group 2. Procedure times between Groups 1 and 2 were similar (228.3 ± 60.2 min vs. 221.3 ± 51.8 min; P = 0.79).

CONCLUSION
An unexpectedly high incidence of thermal EI was noted following PVI using the nMARQ™ with the initial ablation protocol. However, the incidence of thermal EI can be sigificantly reduced with limited power and RF application time at the posterior left atrium.

Rillig|Andreas|A|
Lin|Tina|T|
Burchard|Andre|A|
Kamioka|Masashi|M|
Heeger|Christian|C|
Makimoto|Hisaki|H|
Metzner|Andreas|A|
Wissner|Erik|E|
Wohlmuth|Peter|P|
Ouyang|Feifan|F|
Kuck|Karl-Heinz|KH|
Tilz|Roland Richard|RR|

Multipolar irrigated radiofrequency ablation


Substance use prevention program for adolescents with intellectual disabilities on special education schools: a cluster randomised control trial.

Abstract:
BACKGROUND
Students without intellectual disability (ID) start experimenting with tobacco and alcohol between 12 and 15 years of age. However, data for 12- to 15-year old students with ID are unavailable. Prevention programs, like 'PREPARED ON TIME' (based on the attitude-social influence-efficacy model), are successful, but their efficacy has not been studied in students with ID. The objectives of this study were (1) to undertake a cluster randomised control trial to test the efficacy of the e-learning program among 12- to 15-year old students with mild and borderline ID in secondary special-needs schools and (2) to examine the tobacco and alcohol use for this population.

METHODS
Five schools, randomly selected to be part of either the experimental group or the control group, participated in this study. Passive informed consent was used in which parents and their children can refuse to participate in the study, resulting in 111 students in the experimental group and 143 students in the control group. A total of 210 students completed both baseline and follow-up questionnaires. Primary outcome variables are the knowledge and attitude towards alcohol and tobacco use. This study is registered in the ISRCTN registry with number ISRCTN95279686.

RESULTS
Baseline findings showed that a large proportion of all respondents had initiated smoking (49%) and drinking (75%), well above the expected numbers based on national figures. 'PREPARED ON TIME' did not affect the behavioural determinants (i.e. attitude, subjective norm and self-efficacy), except modelling on smoking. Additionally, alcohol-related knowledge of students in the experimental group increased after the completion of the program.

CONCLUSIONS
To obtain effective results on behavioural outcomes from 'PREPARED ON TIME', a greater degree of flexibility (i.e. repetition, extension of the program, role playing, etc.) is required. Furthermore, prevention needs to be implemented at a younger age, as 6% of the students tried their first cigarette and 15% of the students drank alcohol at the age of 10 years or younger.

Kiewik|M|M|
VanDerNagel|J E L|JE|
Kemna|L E M|LE|
Engels|R C M E|RC|
DeJong|C A J|CA|

D004495:Education of Intellectually Disabled

prevention
adolescents
intellectual disability
special education
alcohol use
tobacco use


Differentiation of human blood from animal blood using Raman spectroscopy: A survey of forensically relevant species.

Abstract: The identification of blood samples is a crucial facet of forensic investigations, particularly for violent crimes. One step in forensic serology (i.e., the analysis of bodily fluids) that is often skipped or overlooked is the determination that a bloodstain is of human or nonhuman origin. Typically, subsequent to identifying a stain as blood using a presumptive blood test, which have the propensity of providing false positive results, the stain is submitted for extraction of a DNA profile to compare with those in a database. It is extremely uncommon that evidentiary bloodstains are confirmed as being of human origin throughout the serological analysis. Therefore, time, money, and other resources can be wasted on obtaining a DNA profile from a bloodstain that may not be of human origin; if the intent was to obtain a human DNA profile and not that of an animal. This work demonstrates an important advancement of a previous study for nondestructive differentiation of human and animal blood using Raman spectroscopy coupled with partial least squares discriminant analysis (PLSDA). Raman spectra of blood from six species of animals, not previously accounted for, including chimpanzee, deer, elk, ferret, fish, and macaque were used to test a PLSDA classification method. These animal species are forensically relevant since they are (i) involved in wildlife crimes, (ii) consumed by humans, or (iii) known to produce a false positive result when their blood is tested with certain presumptive human blood tests. An external validation sensitivity of 1.00 and specificity of 0.93 for human class predictions was obtained from the PLSDA model constructed for this study. Using receiver operating characteristic (ROC) analysis of external human class predictions, the PLSDA model demonstrated 99% accuracy in being able to correctly classify any random blood sample as human or nonhuman. This is a significant advancement over the previous work and a very important finding as it demonstrates the superb selectivity of the developed method with high accuracy in being able to correctly predict the nonhuman origin of bloodstains from unknown animal species.

Partial least squares discriminant analysis (PLSDA)


Potential cytotoxic Diels-Alder type adducts from liquid medium of Morus Alba var. shalun root cultures.

Abstract: A new Diels-Alder type adduct named morushalunin (1), together with three similar compounds, guangsangon E (2), chalcomoracin (3), and kuwanon J (4) were isolated from the EtOAc extract of liquid medium of Morus alba var. shalun root cultures. The structures of the isolated compounds were determined based on spectroscopic data, including 1D, 2D NMR, and MS data. Cytotoxic properties of compounds 1-4 were evaluated against murine leukemia P-388 cells. Morushalunin (1), guangsangon E (2), and chalcomoracin (3) were found to have significant cytotoxicity with IC50 values 0.7, 2.5, and 1.7 μg/mL, respectively, while kuwanon J (4) showed weak cytotoxicity (IC50 = 5.9 μg/mL).

Fitriani|Rizki|R|
Happyana|Nizar|N|
Hakim|Euis Holisotan|EH|

D066241:Carbon-13 Magnetic Resonance Spectroscopy

D066244:Proton Magnetic Resonance Spectroscopy

cytotoxicity
liquid medium
Morus
Morus alba var. shalun
Root cultures
Diels-Alder adducts


Predicting T and N Staging of Resectable Gastric Cancer According to Whole Tumor Histogram Analysis About a Non-Cartesian k-Space Acquisition DCE-MRI: A Feasibility Study.

Abstract:
Objective
To explore the feasibility of the whole tumor histogram analysis parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) based on stack-of stars (StarVIBE) to predict T and N staging of resectable gastric cancer (GC).

Methods
Eighty-seven patients confirmed as GC by histopathology were enrolled in this prospective study. DCE-MRI were performed before surgery, and quantitative DCE parameters (Ktrans, Kep, Ve) and histogram metrics (Skewness, Kurtosis and Entropy) were measured by Omni-Kinetics software. Intraclass correlation coefficient (ICC) testing was used to determine the consistency of Ktrans, Kep and Ve values and histogram metrics values between two radiologists using Bland-Altman analysis. The quantitative DCE parameters or histogram metrics values between T stage or N stage were compared using ANOVA or Kruskal-Wallis testing. Receiver operating characteristic (ROC) analyses was performed to find out the best parameters for identifying T and N staging.

Results
There was statistical difference in Ktrans, Kep, Ve and entropy to identify T staging (P=0.015, 0.033, <0.001, and 0.007, respectively), and in pairwise comparisons of Ve values showed statistically difference between T1+2 and T3 group (P<0.001), T1+2 and T4 group (P<0.001). There were statistical differences in Ve to identify N staging (P=0.041). In ROC analysis, Ve was the best parameter for identifying T staging (AUC: 0.788, the sensitivity and specificity was 0.929 and 0.578, respectively) and N staging (AUC: 0.590, the sensitivity and specificity was 0.714 and 0.899, respectively).

Conclusion
The whole tumor histogram analysis parameters derived from StarVIBE DCE-MRI may be able to quantitatively evaluate T and N staging of GC, so as to help clinical treatment decision optimization.

Yan|Liangliang|L| Qu|Jinrong|J|0000-0001-8751-9988 Li|Jing|J|0000-0003-0532-8171 Zhang|Hongkai|H| Lu|Yanan|Y| Gao|Jianbo|J|

T and N staging
starVIBE
quantitative DCE parameters
histogram metrics
magnetic resonance imaging
stomach neoplasms


Inequality in early childhood chronic health conditions requiring hospitalisation: A data linkage study of health service utilisation and costs.

Abstract:
BACKGROUND
The cost of socioeconomic inequality in health service use among Australian children with chronic health conditions is poorly understood.

OBJECTIVES
To quantify the cost of socioeconomic inequality in health service use among Australian children with chronic health conditions.

METHODS
Cohort study using a whole-of-population linked administrative data for all births in Queensland, Australia, between July 2015 and July 2018. Socioeconomic status was defined by an areas-based measure, grouping children into quintiles from most disadvantaged (Q1) to least disadvantaged (Q5) based on their postcode at birth. Study outcomes included health service utilisation (inpatient, emergency department, outpatient, general practitioner, specialist, pathology and diagnostic imaging services) and healthcare costs.

RESULTS
Of the 238,600 children included in the analysis, 10.4% had at least one chronic health condition. Children with chronic health conditions in Q1 had higher rates of inpatient (6.6, 95% confidence interval [CI] 6.4, 6.7), emergency department (7.2, 95% CI 7.0, 7.5) and outpatient (20.3, 95% CI 19.4, 21.3) service use compared to children with chronic health conditions in Q5. They also had lower rates of general practitioner (37.5, 95% CI 36.7, 38.4), specialist (8.9, 95% CI 8.5, 9.3), pathology (10.7, 95% CI 10.2, 11.3), and diagnostic imaging (4.3, 95% CI 4.2,4.5) service use. Children with any chronic health condition in Q1 incurred lower median out-of-pocket fees than children in Q5 ($0 vs $741, respectively), lower median Medicare funding ($2710, vs $3408, respectively), and higher median public hospital funding ($31, 052 vs $23, 017, respectively).

CONCLUSIONS
Children of most disadvantage are more likely to access public hospital provided services, which are accessible free of charge to patients. These children are less likely to access general practitioner, specialist, pathology and diagnostic imaging services; all of which are critical to the ongoing management of chronic health conditions, but often attract an out-of-pocket fee.

cost
access
equality
private health care
public health care


Pulmonary function tests in ulcerative colitis.

Abstract:
BACKGROUND
Pulmonary impairment in patients suffering ulcerative colitis (UC) has been suggested by several investigators using standard pulmonary function tests (PFTs). This changes in pulmonary function associated with minimal respiratory symptoms have been documented, especially in patients with active disease. The aim of this prospective study was to determine airway resistance and lung volumes in patients with UC who have no respiratory symptoms in comparisons to a healthy control group.

MATERIALS AND METHODS
We evaluated a total of 30 patients with UC by means of spirometry, body plethysmography, and impulse oscillometry. The patients were not complaining of any pulmonary symptoms and did not present any history of previous respiratory diseases. As controls we examined 30 healthy subjects matched for gender, age, and smoking status. The relationship between PFT, lung volume, and airway resistance; and the activity, localization, and duration of the UC disease were analyzed.

RESULTS
There was a significant difference between airway resistances (kPa/L/s) measured by body plethysmography in patients with UC and those of the controls (R5hz; 0.60 ± 0.44 vs. 0.39 ± 0.13; P < 0.001) and R20hz (0.37 ± 0.19 vs. 0.29 ± 0.1, P = 0.02). There were no correlation between PFT, airway resistance and site and scoring activity (P > 0.05).

CONCLUSION
Despite the lack of pulmonary symptoms, increased airway resistance was found in UC patients. We also have not found correlation between PFT, lung volume and airway resistance values and scoring of UC activity.

Amra|Babak|B|
Ataabadi|Ghazal|G|
Emami|Mohamad Hassan|MH|
Hassanzadeh|Akbar|A|
Golshan|Mohammad|M|
Soltaninejad|Forogh|F|

ulcerative colitis
Body plethysmography
impulse oscillometry


The behavioural homing response of adult chum salmon Oncorhynchus keta to amino-acid profiles.

Abstract: Adult chum salmon Oncorhynchus keta homing behaviour in a two-choice test tank (Y-maze) was monitored using a passive integrated transponder (PIT)-tag system in response to river-specific dissolved free amino-acid (DFAA) profiles and revealed that the majority of O. keta showed a preference for artificial natal-stream water and tended to stay in this maze arm for a longer period; natal-stream water was chosen over a nearby tributary's water, but not when the O. keta were presented with a non-tributary water. The results demonstrate the ability of O. keta to discriminate artificial stream waters containing natural levels of DFAA.

Chen|E Y|EY|
Leonard|J B K|JBK|
Ueda|H|H|

homing behaviour
Y-maze
artificial stream waters
PIT tag
dissolved free amino acids


Doctors' trustworthiness, practice orientation, performance and patient satisfaction.

Abstract:
PURPOSE
The purpose of this paper is to provide a greater understanding of the general practitioner (GP)-patient relationship for academics and practitioners. A new model for dyadic professional relationships specifically designed for research into the doctor-patient relationship was developed and tested. Various conceptual models of trust and related constructs in the literature were considered and assessed for their relevance as were various related scales.

DESIGN/METHODOLOGY/APPROACH
The model was designed and tested using purposefully designed scales measuring doctors' trustworthiness, practice orientation performance and patient satisfaction. A quantitative survey used closed-ended questions and 372 patients responded from seven GP practices. The sample closely reflected the profile of the patients who responded to the DoH/NHS GP Patient Survey for England, 2010.

FINDINGS
Hierarchical regression and partial least squares both accounted for 74 per cent of the variance in "overall patient satisfaction", the dependent variable. Trust accounted for 39 per cent of the variance explained, with the other independent variables accounting for the other 35 per cent. ANOVA showed good model fit.

PRACTICAL IMPLICATIONS
The findings on the factors which affect patient satisfaction and the doctor-patient relationship have direct implications for GPs and other health professionals. They are of particular relevance at a time of health reform and change.

ORIGINALITY/VALUE
The paper provides: a new model of the doctor-patient relationship and specifically designed scales to test it; a greater understanding of the effects of doctors' trustworthiness, practice orientation and performance on patient satisfaction; and a new framework for examining the breadth and meaning of the doctor-patient relationship and the management of care from the patient's viewpoint.

Van Den Assem|Barend|B|
Dulewicz|Victor|V|

Patient satisfaction
Trust
Continuity of care
Outcomes
Patient expectation
Patient perception