Risk stratification for implantable cardioverter defibrillator therapy: the role of the wearable cardioverter-defibrillator.

Abstract: The benefit of implantable cardioverter-defibrillator (ICD) therapy depends upon appropriate evaluation of a persisting risk of sudden death and estimation of the patient's overall survival. Assessment of a stable and unchangeable arrhythmogenic substrate is often difficult. Structural abnormality and ventricular dysfunction, the two major risk parameters, may recover, and heart failure symptoms can improve so that ICD therapy may not be indicated. Risk stratification can take time while the patient continues to be at high risk of arrhythmic death, and patients may need temporary bridging by a defibrillator in cases of interrupted ICD therapy. The wearable cardioverter-defibrillator (WCD) combines a long-term electrocardiogram (ECG)-monitoring system with an external automatic defibrillator. The LIfeVest® (ZOLL, Pittsburgh, PA, USA) is composed of a garment, containing two defibrillation patch electrodes on the back, and an elastic belt with a front-defibrillation patch electrode and four non-adhesive ECG electrodes, connected to a monitoring and defibrillation unit. The WCD is a safe and effective tool to terminate ventricular tachycardia/ventricular fibrillation events, unless a conscious patient withholds shock delivery. It may be used in patients in the early phase after acute myocardial infarction with poor left ventricular function, after acute coronary revascularization procedures (percutaneous coronary intervention or coronary artery bypass grafting) and reduced left ventricular ejection fraction (≤35%), in patients with acute heart failure in non-ischaemic cardiomyopathy of uncertain aetiology and prognosis. The WCD may be helpful in subjects with syncope of assumed tachyarrhythmia origin or in patients with inherited arrhythmia syndromes. The WCD may replace ICD implantation in patients waiting for heart transplantation or who need a ventricular-assist device. This review describes the technical details and characteristics of the WCD, discusses its various potential applications, and reports the currently available experience with the wearable defibrillator.

Klein|Helmut U|HU|
Goldenberg|Ilan|I|
Moss|Arthur J|AJ|

D001145:Arrhythmias, Cardiac
D016757:Death, Sudden, Cardiac
D047548:Defibrillators
D017147:Defibrillators, Implantable
D004554:Electric Countershock
D004562:Electrocardiography
D006333:Heart Failure
D016027:Heart Transplantation
D006353:Heart-Assist Devices
D006801:Humans
D011300:Preoperative Care
D011474:Prosthesis Design
D018570:Risk Assessment
D012308:Risk Management
D013575:Syncope

Risk stratification
Wearable cardioverter-defibrillator
ICD therapy
Sudden cardiac death


Auto-Penectomy: A Devastating Complication of Advanced, Neglected Penile Carcinoma: Autopenectomy due to penile carcinoma.

Abstract: Auto-penectomy is a rare consequence of penile carcinoma (PC). Two men, 65 and 74 years of age, presented with total penile loss secondary to PC. Due to poor hygiene and negligence, the ulcer was infected with maggots. The management was by local debridement and suprapubic cystostomy. No further treatment was done as the patients did not come for follow-up.

Kumar|Arvind|A|
Goel|Apul|A|
Sankhwar|Satya N|SN|


Genetic susceptibility to toxicologic lung responses among inbred mouse strains following exposure to carbon nanotubes and profiling of underlying gene networks.

Abstract: The risk of human exposure to fiber nanoparticles has risen in recent years due to increases in the manufacture and utilization of carbon nanotubes (CNTs). CNTs are present as airborne particulates in occupational settings and their hazard potential has been demonstrated in experimental lung exposure studies using inbred mouse strains. However, it is not known whether different inbred strains differ in lung responses to CNTs by virtue of their genetics. In this work, common inbred strains (BALB/c, C57Bl/6, DBA/2, and C3H/He) were exposed to CNTs via oropharyngeal aspiration and lung histology and bronchoalveolar lavage (BAL) samples were evaluated over 28days with the objective of evaluating sensitivity/resistance among strains. C57Bl/6 mice developed significantly more extensive type II pneumocyte (T2P) hyperplasia and alveolar infiltrate compared to DBA/2 mice, which were resistant. Surprisingly, DBA/2 but not C57Bl/6 mice were extremely sensitive to increases in leukocytes recovered in BAL fluid. Underlying global gene expression patterns in the two strains were compared using mRNA sequencing to investigate regulatory networks associated with the different effects. The impact of exposure on gene networks regulating various aspects of immune response and cell survival was limited in DBA/2 mice compared to C57Bl/6. Investigation of B6D2F1 (C57Bl/6×DBA/2 hybrid) mice demonstrated inheritance of sensitivity to CNT exposures in regard to toxicologic lung pathology and BAL leukocyte accumulations. These findings demonstrate a genetic basis of susceptibility to CNT particle exposures and both inform the use of inbred mouse models and suggest the likelihood of differences in genetic susceptibility among humans.

Frank|Evan A|EA|
Carreira|Vinicius S|VS|
Shanmukhappa|Kumar|K|
Medvedovic|Mario|M|
Prows|Daniel R|DR|
Yadav|Jagjit S|JS|

D020022:Genetic Predisposition to Disease

Genetic susceptibility
Carbon nanotubes
Nanoparticles
Inbred strains
Mouse models
Toxicologic pathology


Investigation of O-polysaccharides from bacterial strains of Pseudomonas genus as potential receptors of bacteriophage BIM BV-45.

Abstract: The structure of potential bacteriophage receptors located on cell walls of Gram-negative bacteria deposited at Belarusian collection of microorganisms was investigated. Studies by 1D and 2D 1H and 13C NMR spectroscopy enabled to elucidate the structure of the O-specific polysaccharides (OPS) constituting lipopolysaccharide (LPS) of some Pseudomonas species. The capacity of bacteriophage to adsorb to LPS molecules was tested.

Zdorovenko|Evelina L|EL|
Besarab|Natalya V|NV|
Shashkov|Alexander S|AS|
Novik|Galina I|GI|
Shirokov|Alexander A|AA|
Burov|Andrei M|AM|
Knirel|Yuriy A|YA|

Pseudomonas
Bacteriophages
NMR spectroscopy
Adsorption
Electron microscopy
O-polysaccharides (OPS)


Siloxanes removal from biogas by a lab-scale biotrickling filter inoculated with Pseudomonas aeruginosa S240.

Abstract: Removing volatile methyl siloxanes (VMSs) from biogas remains a longstanding challenge in the field of biological process due to their low bioavailability and biodegradation. To address this issue, a lab-scale aerobic biotrickling filter, packed with porous lava and inoculated with an effective strain of Pseudomonas aeruginosa, was developed and its performance for octamethylcyclotetrasiloxane (D4, selected as a model VMS) removal from an aerobic synthetic gas was monitored. The biotrickling filter exhibited a relatively high removal efficiency over 74% at empty bed residence time of 13.2 min. Rhamnolipids, biosurfactants produced by P. aeruginosa, were identified in the liquid phase of the biotrickling filter by HPLC-MS and ATR-FTIR, and they were found to be the main factor of improving D4 removal. Moreover, dimethylsilanediol, methanol, silicic acid in the liquid phase and carbon dioxide in the gas phase, as the biodegradation products of D4, were determined by GC-MS, silicic acid analysis and non-dispersive infrared analysis. To our knowledge, it is the first time to report the existence of methanol in the D4 degradation products. Finally, a metabolic pathway for D4 degradation by P. aeruginosa was proposed based on our results.

Siloxanes
Biotrickling filter
Pseudomonas aeruginosa
Rhamnolipids
GC–MS


Perceptions of social and environmental changes in a Mediterranean forest during the last 100 years: the Gavarres Massif.

Abstract: During the last century the landscape of the mid-Mediterranean mountains has undergone major transformations. The precipitous decline in the economic viability of forest products has engendered ever-thickening forests and agricultural lands have reverted to forest land cover. The related exodus of existing inhabitants since 1960 has led to new styles of occupancy: residential and touristic land uses have emerged while the primary and secondary sectors have largely disappeared. The object of the present study is to review how these transformations have developed in a specific area of north-eastern of Catalonia, known as the Gavarres Massif. The study applies a qualitative approach, based on interviews with stakeholders including active members of the local community and others who utilize or visit the area, all of whom are representatives of different social groups with a wide range of interests and points of view with regard to the massif. The information collected from the perspectives and opinions of the participants is coupled with objective data about the area. The result of this investigation is a rich variety of perceptions on landscape and social transformation and its current functional dynamics. Analyzing the information obtained allows us to understand the fact that the disappearance of the rural world is directly related to the collapse of an entire economic system that relied on the environment. In this study, two divergent points of view arise, one which supports recovering past landscapes and another which favours managing changes, conserving the existing landscape. Proposals for the current and future territorial management of Les Gavarres are presented. The diversity of opinions which emerges with regard to managing necessary changes in the massif emphasizes the importance of increased social dialogue.

Rodríguez-Carreras|Roser|R| Ubeda|Xavier|X| Outeiro|Luís|L| Asperó|Francesc|F|

D003247:Conservation of Natural Resources

Gavarres
Catalonia
Territorial management
Mediterranean mountains
Sense of place
Social perceptions
Socio-environmental transformations


An investigation into the functional and structural connectivity of the Default Mode Network.

Abstract: Connectivity analyses based on both resting-state (rs-)fMRI and diffusion weighted imaging studies suggest that the human brain contains regions that act as hubs for the entire brain, and that elements of the Default Mode Network (DMN) play a pivotal role in this network. In the present study, the detailed functional and structural connectivity of the DMN was investigated. Resting state fMRI (35 minute duration) and Diffusion Weighted Imaging (DWI) data (256 directions) were acquired from forty-seven healthy subjects at 3 T. Tractography was performed on the DWI data. The resting state data were analysed using a combination of Independent Component Analysis, partial correlation analysis and graph theory. This forms a data driven approach for examining the connectivity of the DMN. ICA defined regions of interest were used as a basis for a partial correlation analysis. The resulting partial correlation coefficients were used to compute graph theoretical measures. This was performed on a single subject basis, and combined to compute group results depicting the spatial distribution of betweenness centrality within the DMN. Hubs with high betweenness centrality were frequently found in association areas of the brain. This approach makes it possible to distinguish the hubs in the DMN as belonging to different anatomical association systems. The start and end points of the fibre tracts coincide with hubs found using the resting state analysis.

van Oort|E S B|ES|
van Cappellen van Walsum|A M|AM|
Norris|D G|DG|

Connectivity
Default Mode Network
Diffusion Weighted Imaging
Hubs
Resting state fMRI
Graph theory


The endocannabinoid system and retinoic acid signaling combine to influence bone growth.

Abstract: Osteoporosis is an increasing burden on public health as the world-wide population ages and effective therapeutics are severely needed. Two pathways with high potential for osteoporosis treatment are the retinoic acid (RA) and endocannabinoid system (ECS) signaling pathways. We sought to elucidate the roles that these pathways play in bone development and maturation. Here, we use chemical treatments to modulate the RA and ECS pathways at distinct early, intermediate, and late times bone development in zebrafish. We further assessed osteoclast activity later in zebrafish and medaka. Finally, by combining sub-optimal doses of AR and ECS modulators, we show that enhancing RA signaling or reducing the ECS promote bone formation and decrease osteoclast abundance and activity. These data demonstrate that RA signaling and the ECS can be combined as sub-optimal doses to influence bone growth and may be key targets for potential therapeutics.

Fraher|Daniel|D|
Mann|Robert J|RJ|
Dubuisson|Matthew J|MJ|
Ellis|Megan K|MK|
Yu|Tingsheng|T|
Walder|Ken|K|
Ward|Alister C|AC|
Winkler|Christoph|C|
Gibert|Yann|Y|

Endocannabinoid
Retinoic acid
Zebrafish
Osteoclast
Medaka
Osteoblast


Responses and recovery pattern of sex steroid hormones in testis of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl.

Abstract: Tilapia were exposed to sublethal methomyl concentrations of 0, 0.2, 2, 20 or 200 μg/L for 30 days, and then transferred to methomyl-free water for 18 days. The sexual steroid hormones 17β-estradiol (E2), testosterone (T), and 11-ketotestosterone (11-KT) in tilapia testes were examined at 0, 6, 12, 18, 24 and 30 days after methomyl exposure, and at 18 days after fish were transferred to methomyl-free water. There were no significant changes in the hormone parameters in testes of tilapia exposed to low concentration 0.2 and 2 μg/L methomyl compared with the controls. However, high concentration 20 and 200 μg/L methomyl had the potential to disrupt the endocrine system of male tilapia, as shown by an increase in E2 and a decrease in T and 11-KT in the testes. Thus, it would appear that the 2 μg/L methomyl might be considered the no-observed-adverse-effect level. Recovery data showed that the effects produced by the lower concentration of 20 μg/L were reversible but the effects were not reversible at the higher concentration of 200 μg/L.

Meng|Shun Long|SL|
Qiu|Li Ping|LP|
Hu|Geng Dong|GD|
Fan|Li Min|LM|
Song|Chao|C|
Zheng|Yao|Y|
Wu|Wei|W|
Qu|Jian Hong|JH|
Li|Dan Dan|DD|
Chen|Jia Zhang|JZ|
Xu|Pao|P|

Recovery pattern
Sex steroid hormone
Testis
Tilapia
Methomyl


Risk factors for pulmonary embolism in patients preliminarily diagnosed with community-acquired pneumonia: a prospective cohort study.

Abstract: D-dimer levels are increased in patients with acute pulmonary embolism (PE). However, D-dimer levels are also increased in patients with community-acquired pneumonia (CAP). The aim of this prospective cohort study was to examine the incidence and clinical features of patients preliminarily diagnosed with CAP and with increased D-dimer levels, and who finally were diagnosed with PE. Patients diagnosed with CAP and hospitalized in the Respiratory Department of the Tenth People's Hospital Affiliated to Tongji University between May 2011 and May 2013 were enrolled. D-dimer levels were measured routinely after admission. For patients with increased D-dimer levels, those suspected with PE underwent computed tomography pulmonary angiography (CTPA). A total of 2387 patients with CAP was included: 724 (30.3 %) had increased D-dimer levels (median of 0.91 mg/L). CTPA was performed for 139 of the 724 patients (median D-dimer levels of 1.99 mg/L). Among the 139 patients, 80 were diagnosed with PE, and 59 without PE; D-dimer levels were 2.83 and 1.41 mg/L, respectively (p < 0.05). Multivariate analysis showed that age, coronary heart disease, chronic obstructive pulmonary disease (COPD), lower limb varicosity, chest pain, shortness of breath, hemoptysis, fever, and increased levels of troponin I were independent risk factors for PE. Presentation of PE and CAP are similar. Nevertheless, these results indicated that for hospitalized patients with CAP and elevated D-dimer levels, PE should be considered for those >60 years; with CHD, COPD, or lower limb varicosity; with chest pain, shortness of breath, hemoptysis, increased troponin I, or low fever.

Zhang|Yunfeng|Y| Zhou|Qixing|Q| Zou|Ying|Y| Song|Xiaolian|X| Xie|Shuanshuan|S| Tan|Min|M| Zhang|Guoliang|G| Wang|Changhui|C|

D005338:Fibrin Fibrinogen Degradation Products

D029424:Pulmonary Disease, Chronic Obstructive

Risk factors
Community-acquired pneumonia
Prospective cohort study
D-dimer
Complications
Pulmonary thromboembolism


Pregnancy complications in women with polycystic ovary syndrome.

Abstract:
BACKGROUND
The great majority of studies performed so far concerning women diagnosed with polycystic ovary syndrome (PCOS) have focused on diagnosis, menstrual cycle abnormalities, hirsutism and infertility. Although progress has been made in developing methods for achieving a pregnancy and reducing multiple gestations in women with PCOS, little attention has been paid to pregnancy complications and subsequent child outcomes. This review aims to summarize current knowledge regarding the clinical and pathophysiological features of pregnancy and children in women with PCOS.

METHODS
A literature search up to April 2015 was performed in PubMed, Medline, the Cochrane Library and Web of Science without language restriction. All articles were initially screened for title and abstract and full texts of eligible articles were subsequently selected. Systematic reviews with meta-analysis were initially included for each specific subject. Recent randomised controlled trials (RCTs), which were not included in the systematic reviews, were also included. In addition to evidence from meta-analyses or RCTs, we used non-randomized prospective, uncontrolled prospective, retrospective and experimental studies. When specific data for patients with PCOS were lacking, results from general population studies were reported.

RESULTS
Women with PCOS exhibit a clinically significant increased risk of pregnancy complications compared with controls. Data which were not adjusted for BMI or other confounders demonstrated in PCOS a 3-4-fold increased risk of pregnancy-induced hypertension and pre-eclampsia, a 3-fold increased risk of gestational diabetes and 2-fold higher chance for premature delivery. Features characteristic of PCOS, such as hyperandrogenism, obesity, insulin resistance and metabolic abnormalities, may contribute to the increased risk of obstetric and neonatal complications. Limited available data suggest that offspring of women with PCOS have an increased risk for future metabolic and reproductive dysfunction. Underlying pathophysiological mechanisms of pregnancy complications along with its association with health of offspring remain uncertain. To date, the strategies for prevention and management of pregnancy complications in women with PCOS, and whether long-term health of these women is influenced, and to what extent, by pregnancy and/or pregnancy complications, remain to be elucidated.

CONCLUSIONS
Women with PCOS show an increased risk of pregnancy complications. Heterogeneous aetiological factors involved in PCOS and associated co-morbidities may all be involved in compromised pregnancy and child outcomes. In women with PCOS, a possible relationship with genetic, environmental, clinical and biochemical factors involved in this complex condition, as well as with pregnancy complications and long-term health for both mother and child, remains to be established.

Palomba|Stefano|S|
de Wilde|Marlieke A|MA|
Falbo|Angela|A|
Koster|Maria P H|MP|
La Sala|Giovanni Battista|GB|
Fauser|Bart C J M|BC|

D011297:Prenatal Exposure Delayed Effects

D016032:Randomized Controlled Trials as Topic

pregnancy
complications
polycystic ovary syndrome
PCOS
obstetrics


Taurocholic acid metabolism by gut microbes and colon cancer.

Abstract: Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively.

Ridlon|Jason M|JM|
Wolf|Patricia G|PG|
Gaskins|H Rex|HR|

colon cancer
diet
bile acid
deoxycholic acid
taurine
hydrogen sulfide


Potential cardiovascular implications of Sea Buckthorn berry consumption in humans.

Abstract: Diets rich in fruits and vegetables have been correlated with decreased risks of cardiovascular disease. Particularly, berry consumption has been associated with reductions in cardiovascular risk. Despite the range of potentially beneficial phytochemical components (vitamins, polyphenols, carotenoids, and fatty acids), there is little evidence underpinning the cardiovascular effects of sea buckthorn (SB) berries. The purpose of this review is to evaluate the benefits of SB consumption on cardiovascular health in human trials. Only six human studies were found, which examine the effect of SB berries on cardiovascular outcomes (i.e., lipid metabolism, platelet aggregation, and inflammation). Although there appears to be an inverse association between SB consumption and cardiovascular risk factors, the evidence is still scarce and the results are inconsistent. In addition, limitations in study design made it difficult to form firm conclusions. More "high-quality" human clinical trials are needed in order to establish the cardio-protective benefits of SB berries.

sea buckthorn berries
platelet aggregation
inflammation
Blood lipids
phytonutrients


Treatment of Femoral Vein Obstruction Concomitant with Iliofemoral Stenting in Patients with Severe Post-thrombotic Syndrome.

Abstract:
BACKGROUND
The aim was to assess the clinical and anatomical outcomes of iliofemoral stenting, with concomitant femoral stenting or balloon angioplasty alone, in patients with severe post-thrombotic syndrome (PTS) and compromised inflow.

METHODS
A database of patients with severe PTS who successfully underwent endovascular iliofemoral stenting was reviewed retrospectively. Patients with impaired inflow with chronic post-thrombotic obstructive lesions in the femoral vein (FV), but patent profunda vein, were selected and divided into two groups: the FV stenting (FV-S) group and the FV angioplasty (FV-A) group. Patients in the FV-S group were treated with concomitant iliofemoral and FV stenting, and patients in the FV-A group were treated with iliofemoral stenting and balloon angioplasty alone of the obstructed femoral vein. The clinical and stent outcomes were recorded and compared in the two groups.

RESULTS
There were 45 patients in the FV-S group and 69 patients in the FV-A group. The groups were well matched for age, gender, and diseased limbs. The pre-procedural symptoms, CEAP classifications, VCSS scores, Villalta scores, and prevalence of active ulcers were also similar between the two groups. Immediate failure (<30 days post-procedure) in the femoral segment occurred more frequently in the FV-A group (70% in FV-A group vs. 24% in FV-S group, p < .001); however, all treated femoral vein segments had occluded at 12 months. There was no significant difference between the FV-S and FV-A groups in cumulative primary and secondary patency rates of the iliofemoral stent at 3 years (55% vs. 52%, p = .71, and 77% vs. 85%, p = .32, respectively). Complete pain relief, swelling relief, VCSS score, Villalta score, and freedom from ulcers at a median of 22 months (1-48 months) following the procedure were similar in the two groups.

CONCLUSIONS
Stent placement to treat post-thrombotic iliofemoral obstruction with concomitant obstructed femoral vein but patent profunda vein shows cumulative patency rates and clinical outcomes similar to previous reports. Adjunctive femoral stenting or angioplasty of the obstructed femoral vein does not appear to improve clinical or stent outcomes in patients with severe PTS.

Ye|Kaichuang|K| Shi|Huihua|H| Yin|Minyi|M| Qin|Jinbao|J| Yang|Xinrui|X| Liu|Xiaobing|X| Jiang|Mier|M| Lu|Xinwu|X|

D019917:Blood Vessel Prosthesis Implantation

Femoral vein
Stent
Post-thrombotic syndrome
Chronic post-thrombotic obstruction
Iliac vein


Anomalous relaxation and the high-temperature structure factor of XXZ spin chains.

Abstract: We compute the spin-structure factor of XXZ spin chains in the Heisenberg and gapped (Ising) regimes in the high-temperature limit for nonzero magnetization, within the framework of generalized hydrodynamics, including diffusive corrections. The structure factor shows a hierarchy of timescales in the gapped phase, owing to s-spin magnon bound states ("strings") of various sizes. Although short strings move ballistically, long strings move primarily diffusively as a result of their collisions with short strings. The interplay between these effects gives rise to anomalous power-law decay of the spin-structure factor, with continuously varying exponents, at any fixed separation in the late-time limit. We elucidate the cross-over to diffusion (in the gapped phase) and to superdiffusion (at the isotropic point) in the half-filling limit. We verify our results via extensive matrix product operator calculations.

matrix product operators
anomalous diffusion
integrable systems
spin transport


Translocation of Trace Elements from Sewage Sludge Amendments to Plants in a Reclaimed Area.

Abstract: The goal of the study was to evaluate bioaccumulation of trace elements in plants grown in post-mining soils amended with the biosolids material. Phaseolus vulgaris was investigated on the laboratory scale, and a mixture of grasses, Melilotus albus, Beta vulgaris, Zea mays L. and Miscanthus × giganteus were evaluated on the field scale. The results of the research showed that P. vulgaris fertilized with the Carbocrash substrate was able to grow. In addition, growth was enhanced following stimulation with gibberellic acid. Transfer of trace elements should be evaluated on the plot scale. Therefore, we monitored the level of trace elements on an experimental plot in a reclaimed area. Crops plants were sown in multi-year periods. During the growing season the mixture of grasses and crop plants had a low bioaccumulation factor, which also showed a positive effect of fertilization with the Carbocrash substrate.

Trace elements
Biosolids
Bioaccumulation factor
Land reclamation
Plant growth stimulation


Fifty Years of Mountain Passes: A Perspective on Dan Janzen's Classic Article.

Abstract: In 1967, Dan Janzen published "Why Mountain Passes Are Higher in the Tropics" in The American Naturalist. Janzen's seminal article has captured the attention of generations of biologists and continues to inspire theoretical and empirical work. The underlying assumptions and derived predictions are broadly synthetic and widely applicable. Consequently, Janzen's "seasonality hypothesis" has proven relevant to physiology, climate change, ecology, and evolution. To celebrate the fiftieth anniversary of this highly influential article, we highlight the past, present, and future of this work and include a unique historical perspective from Janzen himself.

Sheldon|Kimberly S|KS|
Huey|Raymond B|RB|
Kaspari|Michael|M|
Sanders|Nathan J|NJ|

tropics
seasonality
dispersal
geographic range size
temperature variation
thermal sensitivity


Adhering to the principles of clinical pharmacology - the correct fixed combinations of antihypertensive drugs.

Abstract: Hypertension is one of the primary modifiable risk factor for cardiac and renal diseases with the prevalence around 30-45% of the general population, with a steep increase with ageing. The administration of blood pressure-lowering drugs is to reduce the risk of major clinical cardiovascular outcomes. Hypertension guidelines recommend combination therapy in patients with high cardiovascular risk and with subclinical organ damage as well as when monotherapy fails. Areas covered: As the etiology of essential hypertension is multifactorial, combination therapy using different classes of antihypertensive agents have greater effect than each on its own (synergistic effect), may have better tolerability (two components minimizing each other's side effects) and lead to improved patient compliance. Several studies assess the hypotensive efficacy on drug combination; there are also studies on triple drug combination. Expert commentary: At present, dual and triple combination therapy is available to hypertensive patients with good clinical outcomes, compliance and low profile of side effects. It is critical as patients' adherence to the pharmacological therapy significantly decreases the risk of long-term adverse events including mortality. It appears that combinations not only of hypotensive drugs but also with statins (as well as antidiabetics) will be widely used.

Lopatowska|Paulina|P| Mlodawska|Elzbieta|E| Tomaszuk-Kazberuk|Anna|A| Banach|Maciej|M| Malyszko|Jolanta|J|

D000959:Antihypertensive Agents
D001794:Blood Pressure
D002318:Cardiovascular Diseases
D004338:Drug Combinations
D004357:Drug Synergism
D004359:Drug Therapy, Combination
D006801:Humans
D006973:Hypertension
D055118:Medication Adherence
D017410:Practice Guidelines as Topic
D012307:Risk Factors

Antihypertensive drugs
combination therapy
single pill combination


Marasmius oreades agglutinin enhances resistance of Arabidopsis against plant-parasitic nematodes and a herbivorous insect.

Abstract:
BACKGROUND
Plant-parasitic nematodes and herbivorous insects have a significant negative impact on global crop production. A successful approach to protect crops from these pests is the in planta expression of nematotoxic or entomotoxic proteins such as crystal proteins from Bacillus thuringiensis (Bt) or plant lectins. However, the efficacy of this approach is threatened by emergence of resistance in nematode and insect populations to these proteins. To solve this problem, novel nematotoxic and entomotoxic proteins are needed. During the last two decades, several cytoplasmic lectins from mushrooms with nematicidal and insecticidal activity have been characterized. In this study, we tested the potential of Marasmius oreades agglutinin (MOA) to furnish Arabidopsis plants with resistance towards three economically important crop pests: the two plant-parasitic nematodes Heterodera schachtii and Meloidogyne incognita and the herbivorous diamondback moth Plutella xylostella.

RESULTS
The expression of MOA does not affect plant growth under axenic conditions which is an essential parameter in the engineering of genetically modified crops. The transgenic Arabidopsis lines showed nearly complete resistance to H. schachtii, in that the number of female and male nematodes per cm root was reduced by 86-91 % and 43-93 % compared to WT, respectively. M. incognita proved to be less susceptible to the MOA protein in that 18-25 % and 26-35 % less galls and nematode egg masses, respectively, were observed in the transgenic lines. Larvae of the herbivorous P. xylostella foraging on MOA-expression lines showed a lower relative mass gain (22-38 %) and survival rate (15-24 %) than those feeding on WT plants.

CONCLUSIONS
The results of our in planta experiments reveal a robust nematicidal and insecticidal activity of the fungal lectin MOA against important agricultural pests which may be exploited for crop protection.

Moradi|Aboubakr|A|
Austerlitz|Tina|T|
Dahlin|Paul|P|
Robert|Christelle Am|CA|
Maurer|Corina|C|
Steinauer|Katja|K|
van Doan|Cong|C|
Himmighofen|Paul Anton|PA|
Wieczorek|Krzysztof|K|
Künzler|Markus|M|
Mauch|Felix|F|

D018506:Gene Expression Regulation, Plant

Marasmius oreades agglutinin
Arabidopsis
Heterodera schachtii
Meloidogyne incognita
Plutella xylostella


Trends and Developments in Mindfulness Research over 55 Years: A Bibliometric Analysis of Publications Indexed in Web of Science.

Abstract:
Objectives
This study aimed to identify historical developments, active research areas, and emerging trends within scientific literature on mindfulness published so far, using bibliometric methods. We also aimed to identify prominent journals, authors, organizations, and countries in the field of mindfulness.

Methods
Articles or reviews which mention mindfulness in the title, abstract, or keywords were identified using the Web of Science. A descriptive summary of the literature was obtained from the Web of Science Analysis tool. Country collaboration, co-authorship, and keyword co-occurrence networks were visualized using VOSviewer. CiteSpace, which uses document co-citation analysis, was used to identify emerging trends and transient patterns in the literature.

Results
From 1966 to 2021, 16,581 publications on mindfulness were identified. There has been an exponential growth of publications since 2006. Almost half (47%) of the publications were in psychology and about one-fifth (20.8%) in psychiatry. The most prolific journal was Mindfulness (contributing 7% of all publications) and the most prolific author was Eric L. Garland. The vast majority of publications originated from Western countries but representation from Asian countries has increased. The most frequently co-occurring keywords were meditation, depression, stress, and anxiety. Co-citation analysis of the early period (1966-2015) revealed how scholarly work on spiritual themes has inspired early mindfulness research. Recent trends (2016-2021) revealed a rising interest in mechanisms and moderators, long-term meditation, neuroscientific studies, and smartphone/online delivery of interventions.

Conclusions
This comprehensive bibliometric study summarized and visualized 55 years of mindfulness research, revealing pivotal points, active research areas, and emerging trends.

Trends
Mindfulness
Bibliometrics
Co-citation analysis
Patterns


Delayed pacemaker requirement after transcatheter aortic valve implantation with a new-generation balloon expandable valve: Should we monitor longer?

Abstract:
OBJECTIVES
To analyze the timing of appearance of conduction abnormalities (CAs) after transcatheter aortic valve implantation (TAVI), to identify predictors of delayed CAs requiring pacemaker (PM) implantation and to provide guidance regarding the duration of telemetry monitoring.

BACKGROUND
How long patients remain at risk of development of CAs requiring PM implantation after TAVI and for how long they should be monitored remains unclear but is crucial when considering early discharge.

METHODS
Development of CAs was studied in 701 consecutive patients treated with Edwards Sapien 3 valves and monitored with telemetry for 7 days in a single center. After excluding valve-in-valve procedures and patients with previous PM, 606 patients remained for analysis. Predictors of CAs requiring PM and the time of onset of CAs were analyzed.

RESULTS
Of 606 patients 76 (12.5%) required a PM after TAVI. CAs requiring PM implantation occurred after 48 h in 22.4% (17 patients) and in 10.5% (8 patients) even after 5 days. Of the patients who developed high grade CAs requiring PM after 48 h, 47.1% had no CAs prior to TAVI, and 23.5% had neither pre-existing CAs nor new-developed CAs within the first 48 h after TAVI.

CONCLUSION
After TAVI using a new-generation balloon-expandable valve, delayed development of CAs requiring PM implantation is not uncommon, even after 5 days. More importantly, 23.5% of patients eventually requiring a delayed PM implantation had still no CAs at 48 h after TAVI in this study. These results question the safety of early discharge and support ECG monitoring for a longer time period. The most optimal way to monitor these patients is yet to be determined.

De-Torres-Alba|Fernando|F| Kaleschke|Gerrit|G| Vormbrock|Julia|J| Orwat|Stefan|S| Radke|Robert|R| Feurle|Monika|M| Diller|Gerhard-Paul|GP| Reinecke|Holger|H| Baumgartner|Helmut|H|

D065467:Transcatheter Aortic Valve Replacement

Transcatheter aortic valve interventions


In support of "no-fault" civil liability rules for artificial intelligence.

Abstract: Civil liability is traditionally understood as indirect market regulation, since the risk of incurring liability for damages gives incentives to invest in safety. Such an approach, however, is inappropriate in the markets of artificial intelligence devices. In fact, according to the current paradigm of civil liability, compensation is allowed only to the extent that "someone" is identified as a debtor. However, in many cases it would not be useful to impose the obligation to pay such compensation to producers and programmers: the algorithms, in fact, can "behave" far independently from the instructions initially provided by programmers so that they can err despite no flaw in design or implementation. Therefore, application of "traditional" civil liability to AI may represent a disincentive to new technologies based on artificial intelligence. This is why I think artificial intelligence requires that the law evolves, on this matter, from an issue of civil liability into one of financial management of losses. No-fault redress schemes could be an interesting and worthy regulatory strategy in order to enable this evolution. Of course, such schemes should apply only in cases where there is no evidence that producers and programmers have acted under conditions of negligence, imprudence or unskillfulness and their activity is adequately compliant with scientifically validated standards.

No-fault
Civil liability
Artificial intelligence
Robots
Self driving cars
Tort law


Trends and characteristics of ocular exposures related to e-cigarettes and e-liquids reported to Poison Control Centers in the United States, 2010-2019.

Abstract:
INTRODUCTION
Ocular injuries and unintended exposures involving electronic nicotine delivery systems (ENDS), also known as e-cigarettes, have been reported. However, trends and characteristics of ENDS-related ocular exposures at the population level are not well documented. This study was designed to describe trends and characteristics of ENDS-related ocular exposure cases reported to poison control centers (PCCs) in the U.S.

METHODS
We computed descriptive statistics of ENDS-related ocular exposure cases reported to PCCs between January 1, 2010 and December 31, 2019, including number of cases per year and the distribution of characteristics of those cases. We also summarized case narrative review findings.

RESULTS
A total of 1,393 ENDS-related ocular exposure cases were reported to PCCs during the study period. Overall number of cases increased from two in 2010 to a peak of 389 in 2014, followed by a steady decline in 2015-2018. Of the 1,393 cases, 42.5% occurred among individuals aged 25 years and older; 20.4 and 17.7% occurred among young adults aged 18-24 years and children younger than five years, respectively. Nearly one quarter (23.8%) of the individuals experiencing ocular exposure sought or were recommended to seek medical attention. Case narrative review found that 59 of 127 (46.5%) cases were due, at least in part, to incorrect use or handling of the products.

DISCUSSION AND CONCLUSIONS
Our study shows that more than 1,000 ENDS-related ocular exposure cases were reported to PCCs during the study period. Many of these cases involved young children; nearly half were due, at least in part, to incorrect use or handling of the products. Future efforts to prevent these exposures may focus on improving the awareness of the potential harmful effects of ENDS products and the importance of appropriate handling of ENDS products. Health care professionals may play an important role in educating patients and improving surveillance of ENDS-related ocular exposure cases.

ocular
e-cigarette
poison
Electronical nicotine delivery systems
ENDS


Perioperative management of antithrombotic treatment during implantation or revision of cardiac implantable electronic devices: the European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI).

Abstract: The European Snapshot Survey on Procedural Routines for Electronic Device Implantation (ESS-PREDI) was a prospective European survey of consecutive adults who had undergone implantation/surgical revision of a cardiac implantable electronic device (CIED) on chronic antithrombotic therapy (enrolment March-June 2015). The aim of the survey was to investigate perioperative treatment with oral anticoagulants and antiplatelets in CIED implantation or surgical revision and to determine the incidence of complications, including clinically significant pocket haematomas. Information on antithrombotic therapy before and after surgery and bleeding and thromboembolic complications occurring after the intervention was collected at first follow-up. The study population comprised 723 patients (66.7% men, 76.9% aged ≥66 years). Antithrombotic treatment was continued during surgery in 489 (67.6%) patients; 6 (0.8%) had their treatment definitively stopped; 46 (6.4%) were switched to another antithrombotic therapy. Heparin bridging was used in 55 out of 154 (35.8%) patients when interrupting vitamin K antagonist (VKA) treatment. Non-vitamin K oral anticoagulant (NOAC) treatment was interrupted in 88.7% of patients, with heparin bridging in 25.6%, but accounted for only 25.3% of the oral anticoagulants used. A total of 108 complications were observed in 98 patients. No intracranial haemorrhage or embolic events were observed. Chronic NOAC treatment before surgery was associated with lower rates of minor pocket haematoma (1.4%; P= 0.042) vs. dual antiplatelet therapy (13.0%), VKA (11.4%), VKA + antiplatelet (9.2%), or NOAC + antiplatelet (7.7%). Similar results were observed for bleeding complications (P= 0.028). Perioperative management of patients undergoing CIED implantation/surgical revision while on chronic antithrombotic therapy varies, with evidence of a disparity between guideline recommendations and practice patterns in Europe. Haemorrhagic complications were significantly less frequent in patients treated with NOACs. Despite this, the incidence of severe pocket haematomas was low.

Deharo|Jean-Claude|JC|
Sciaraffia|Elena|E|
Leclercq|Christophe|C|
Amara|Walid|W|
Doering|Michael|M|
Bongiorni|Maria G|MG|
Chen|Jian|J|
Dagres|Nicolaus|N|
Estner|Heidi|H|
Larsen|Torben B|TB|
Johansen|Jens B|JB|
Potpara|Tatjana S|TS|
Proclemer|Alessandro|A|
Pison|Laurent|L|
Brunet|Caroline|C|
Blomström-Lundqvist|Carina|C|
|||

Cardiac implantable electronic device
Antithrombotic therapy
Antiplatelet
Pocket haematoma
Bleeding
Non-vitamin K oral anticoagulants
EHRA survey
Warfarin


Platelet-Rich Plasma Versus Hyaluronic Acid Injections for the Treatment of Knee Osteoarthritis: Results at 5 Years of a Double-Blind, Randomized Controlled Trial.

Abstract:
BACKGROUND
Platelet-rich plasma (PRP) injections have been proposed as a new conservative option for knee degeneration to provide symptomatic relief and delay surgical intervention. Although the current literature provides some evidence on the benefits of this technique compared with viscosupplementation, no studies have been performed to compare their long-term effects.

PURPOSE
To compare the long-term clinical outcomes provided by intra-articular injections of either PRP or hyaluronic acid (HA) to treat knee degenerative disease.

STUDY DESIGN
Randomized controlled trial; Level of evidence, 1.

METHODS
Patients with a history of chronic symptomatic knee degenerative changes and osteoarthritis (Kellgren-Lawrence grade 0-3) were enrolled: 192 patients were randomized to undergo 3 blinded weekly intra-articular injections of either PRP or HA. Patients were prospectively evaluated before the injection and then at 2, 6, 12, and 24 months and a mean of 64.3 months (SD, 7.8 months) of follow-up. Evaluation was based on International Knee Documentation Committee (IKDC) subjective (main outcome), EuroQol visual analog scale, and Tegner scores; 167 patients reached the final evaluation.

RESULTS
Both treatments were effective in improving knee functional status and symptoms over time: Mean ± SD IKDC subjective score improved significantly for both PRP and HA groups ( P < .0005) and remained stable over time up to 24 months (from 53.3 ± 14.3 to 67.3 ± 18.1 and from 50.3 ± 13.2 to 62.1 ± 20.8 for PRP and HA groups, respectively). At final evaluation, a significant IKDC reduction was observed in both treatment groups, with the PRP group still presenting significantly higher values compared with baseline: PRP 60.5 ± 19.0 ( P < .001 vs baseline), HA 55.7 ± 18.8 (not significant vs baseline). A comparative analysis showed no significant intergroup difference in any of the clinical scores at any follow-up point. The median duration of patient subjective perception of symptomatic relief was 9 months for HA and 12 months for PRP (not significant). The only significant difference was observed in the rate of reintervention at 24 months, which was significantly lower in the PRP group (22.6% vs 37.1%, P = .036).

CONCLUSION
Both treatments were effective in improving knee functional status and symptoms over time. PRP did not provide an overall superior clinical improvement compared with HA in terms of either symptomatic-functional improvement at different follow-up points or effect duration.

REGISTRATION
NCT01670578 (ClinicalTrials.gov identifier).

Di Martino|Alessandro|A|
Di Matteo|Berardo|B|
Papio|Tiziana|T|
Tentoni|Francesco|F|
Selleri|Filippo|F|
Cenacchi|Annarita|A|
Kon|Elizaveta|E|
Filardo|Giuseppe|G|

platelet-rich plasma
injections
osteoarthritis
viscosupplementation
intra-articular
cartilage
growth factors


Renal biopsy: it is time for pragmatism and consensus.

Abstract: To obtain truly informed consent, we must be able to advise our patients accurately about the relative risk and benefit of any treatment plan. Percutaneous renal biopsy remains the gold standard investigation in the evaluation of intrinsic renal disease. There have been significant improvements in practice over the past decades with regards to percutaneous renal biopsy. Across centres, we appear now to have reached agreement on many aspects of this procedure, such as the need for blood pressure control, avoidance of coagulopathy, use of spring-loaded needles under direct imaging guidance and a need to monitor for complications. The authors from Rush University Medical Centre provide reassurance that renal biopsy in the modern era remains a safe procedure with a low rate of significant bleeding. There remain areas of divergence in practice that may have unintended and deleterious consequences: administration of desmopressin and discontinuation of aspirin, for example, both carry a risk of thrombosis. It is our opinion that it is time to reach consensus on our interpretation of the available data and to draw up guidelines to standardize our biopsy practice internationally.

Lees|Jennifer S|JS|
McQuarrie|Emily P|EP|
Mackinnon|Bruce|B|

renal biopsy complication bleeding aspirin


Cost-effective survival prediction for patients with advanced prostate cancer using clinical trial and real-world hospital registry datasets.

Abstract:
INTRODUCTION
Predictive survival modeling offers systematic tools for clinical decision-making and individualized tailoring of treatment strategies to improve patient outcomes while reducing overall healthcare costs. In 2015, a number of machine learning and statistical models were benchmarked in the DREAM 9.5 Prostate Cancer Challenge, based on open clinical trial data for metastatic castration resistant prostate cancer (mCRPC). However, applying these models into clinical practice poses a practical challenge due to the inclusion of a large number of model variables, some of which are not routinely monitored or are expensive to measure.

OBJECTIVES
To develop cost-specified variable selection algorithms for constructing cost-effective prognostic models of overall survival that still preserve sufficient model performance for clinical decision making.

METHODS
Penalized Cox regression models were used for the survival prediction. For the variable selection, we implemented two algorithms: (i) LASSO regularization approach; and (ii) a greedy cost-specified variable selection algorithm. The models were compared in three cohorts of mCRPC patients from randomized clinical trials (RCT), as well as in a real-world cohort (RWC) of advanced prostate cancer patients treated at the Turku University Hospital. Hospital laboratory expenses were utilized as a reference for computing the costs of introducing new variables into the models.

RESULTS
Compared to measuring the full set of clinical variables, economic costs could be reduced by half without a significant loss of model performance. The greedy algorithm outperformed the LASSO-based variable selection with the lowest tested budgets. The overall top performance was higher with the LASSO algorithm.

CONCLUSION
The cost-specified variable selection offers significant budget optimization capability for the real-world survival prediction without compromising the predictive power of the model.

Murtojärvi|Mika|M|
Halkola|Anni S|AS|
Airola|Antti|A|
Laajala|Teemu D|TD|
Mirtti|Tuomas|T|
Aittokallio|Tero|T|
Pahikkala|Tapio|T|

Survival prediction
Prostate cancer
Cost optimization
Feature selection


Initial geochemical characteristics of fluid fine tailings in an oil sands end pit lake.

Abstract: Geochemical characteristics of fluid fine tailings (FFT) were examined in Base Mine Lake (BML), which is the first full-scale demonstration oil sands end pit lake (EPL) in northern Alberta, Canada. Approximately 186Mm(3) of FFT was deposited between 1994 and 2012, before BML was established on December 31, 2012. Bulk FFT samples (n=588) were collected in July and August 2013 at various depths at 15 sampling sites. Temperature, solid content, electrical conductivity (EC), pH, Eh and alkalinity were measured for all samples. Detailed geochemical analyses were performed on a subset of samples (n=284). Pore-water pH decreased with depth by approximately 0.5 within the upper 10m of the FFT. Major pore-water constituents included Na (880±96mgL(-1)) and Cl (560±95mgL(-1)); Ca (19±4.1mgL(-1)), Mg (11±2.0mgL(-1)), K (16±2.3mgL(-1)) and NH3 (9.9±4.7mgL(-1)) were consistently observed. Iron and Mn concentrations were low within FFT pore water, whereas SO4 concentrations decreased sharply across the FFT-water interface. Geochemical modeling indicated that FeS(s) precipitation was favoured under SO4-reducing conditions. Pore water was also under-saturated with respect to gypsum [CaSO4·2H2O], and near saturation with respect to calcite [CaCO3], dolomite [CaMg(CO3)2] and siderite [FeCO3]. X-ray diffraction (XRD) suggested that carbonate-mineral dissolution largely depleted calcite and dolomite. X-ray absorption near edge structure (XANES) spectroscopy revealed the presence of FeS(s), pyrite [FeS2], and siderite. Carbonate-mineral dissolution and secondary mineral precipitation have likely contributed to FFT dewatering and settlement. However, the long-term importance of these processes within EPLs remains unknown. These results provide a reference for assessing the long-term geochemical evolution of oil sands EPLs, and offer insight into the chemistry of pore water released from FFT to the overlying water cover.

Dompierre|Kathryn A|KA|
Lindsay|Matthew B J|MB|
Cruz-Hernández|Pablo|P|
Halferdahl|Geoffrey M|GM|

Tailings
Oil sands
End pit lakes
Mine closure
Process-affected water
Reclamation


Curcumin loaded sub-30 nm targeting therapeutic lipid nanoparticles for synergistically blocking nasopharyngeal cancer growth and metastasis.

Abstract: Systemic chemotherapy is still the primary treatment for advanced-stage nasopharyngeal carcinoma (NPC), but only limited therapeutic success has been achieved in the past decade because of drug resistance and systemic toxicity. Curcumin (Cur) is an effective alternative to chemotherapeutics because it showed remarkable therapeutic potential in the treatment of NPC. However, lack of tissue specificity and poor penetration in solid tumors are the major obstacles to effective therapy. Therefore, in this work, a self-assembled sub-30 nm therapeutic lipid nanoparticle loaded with Cur, named as Cur@α-NTP-LN, was constructed, specifically targeting scavenger receptor class B member 1 (SR-B1) and enhancing its therapeutic effects on NPC in vivo. Our results showed that Cur@α-NTP-LNs were effective and superior to free Cur on NPC cell-specific targeting, suppressing cell proliferation and inducing cell apoptosis. In vivo and ex vivo optical imaging revealed that Cur@α-NTP-LNs exerted high targeting efficiency, specifically accumulating in NPC xenograft tumors and delivering Cur into the tumor center after systemic administration. Furthermore, Cur@α-NTP-LNs exhibited a remarkable inhibitory effect on the growth of NPC subcutaneous tumors, with over 71 and 47% inhibition compared to Cur- and α-NTP-LNs-treated groups, respectively. In addition, Cur@α-NTP-LNs almost blocked NPC metastasis in a lung metastasis model of NPC and significantly improved the survival rate. Thus, the sub-30 nm Cur@α-NTP-LNs enhanced the solubility of Cur and demonstrated the ability of targeted Cur delivery into the center of the solid NPC tumor, performing synergistic inhibitory effects on the growth of NPC tumor and its metastasis with high efficiency.

Curcumin
Lipid nanoparticles
Nasopharyngeal carcinoma
Peptide
Targeted therapy


Fluorescent nuclear track detectors for alpha radiation microdosimetry.

Abstract:
BACKGROUND
While alpha microdosimetry dates back a couple of decades, the effects of localized energy deposition of alpha particles are often still unclear since few comparative studies have been performed. Most modern alpha microdosimetry studies rely for large parts on simulations, which negatively impacts both the simplicity of the calculations and the reliability of the results. A novel microdosimetry method based on the Fluorescent Nuclear Track Detector, a versatile tool that can measure individual alpha particles at sub-micron resolution, yielding accurate energy, fluence and dose rate measurements, was introduced to address these issues.

METHODS
Both the detectors and U87 glioblastoma cell cultures were irradiated using an external Am241 alpha source. The alpha particle tracks measured with a Fluorescent Nuclear Track Detector were used together with high resolution 3D cell geometries images to calculate the nucleus dose distribution in the U87 glioblastoma cells. The experimentally obtained microdosimetry parameters were thereafter applied to simulations of 3D U87 cells cultures (spheroids) with various spatial distributions of isotopes to evaluate the effect of the nucleus dose distribution on the expected cell survival.

RESULTS
The new experimental method showed good agreement with the analytically derived nucleus dose distributions. Small differences (< 5%) in the relative effectiveness were found for isotopes in the cytoplasm and on the cell membrane versus external irradiation, while isotopes located in the nucleus or on the nuclear membrane showed a substantial increase in relative effectiveness (33 - 51%).

CONCLUSIONS
The ease-of-use, good accuracy and use of experimentally derived characteristics of the radiation field make this method superior to conventional simulation-based microdosimetry studies. Considering the uncertainties found in alpha radionuclide carriers in-vivo and in-vitro, together with the large contributions from the relative biological effectiveness and the oxygen enhancement ratio, it is expected that only carriers penetrating or surrounding the cell nucleus will substantially benefit from microdosimetry.

Fluorescent nuclear track detector
Alpha radiation
Microdosimetry
Spheroid
Alpha radionuclide therapy
FNTD


A Designed Experiment: Polymorphism Analysis of Angiotensin-Converting Enzyme Gene from Human Buccal Epithelial Cells.

Abstract: For medical students, we combine the laboratory practice with clinical applications by developing biochemical and molecular biology experiments. In this experiment, students first collect their own buccal epithelial cells by a noninvasive mouthwash method. Then, they extract genomic DNA and perform polymerase chain reaction (PCR) to amplify angiotensin-converting enzyme (ACE) gene using genomic DNA as a template. Finally, the polymorphism of ACE gene is observed by electrophoresis. Students not only learn the techniques but also acquire knowledge of the ACE gene polymorphism. By establishing the relationship among ACE polymorphism and high blood pressure and myocardial hypertrophy, students should be able to understand the gene polymorphism and its association with susceptibility to disease. This laboratory practice teaching can also stimulate desire to do scientific research. Experimental results from many individuals can help us determine and analyze the fractions of ACE gene types in Chinese cohorts. Such an experiment strongly activates students and provides a solid foundation for the medical students' future research and clinical application. © 2019 International Union of Biochemistry and Molecular Biology, 47(2): 168-174, 2019.

Jiao|Li|L|0000-0001-9446-5076 Xueli|Li|L| Xiujuan|Shi|S| Song|Jia|J| Jie|Xu|X| Lixia|Lv|L| Wenzhuo|Yang|Y| Lei|Xu|X|

D004847:Epithelial Cells
D006801:Humans
D007753:Laboratories
D007703:Peptidyl-Dipeptidase A
D011110:Polymorphism, Genetic
D013337:Students, Medical

Laboratory practice
ACE
gene polymorphism
gene diagnosis


Advantages of Short-term Personalized Vestibular Rehabilitation at Home Guided by Professional Therapist for Treatment of Decompensated Vestibular Vertigo.

Abstract:
OBJECTIVE
Patients suffered a lot from decompensated vestibular vertigo. Pharmacotherapy and vestibular rehabilitation training have been proven to be effective in prompting vestibular compensation. Routine rehabilitation training is faced with the challenges of patients' compliance, completion, the average recuperation time and so on. This study is aimed to investigate advantages of short-term personalized vestibular rehabihitation at home guided by professional therapist.

METHODS
A short-term personalized vestibular rehabilitation program (ST-PVR) was designed for patients with decompensated vestibular vertigo in this study.

RESULTS
Patients experiencing the ST-PVR program showed significant improvement of Self-Rating Anxiety Scale (SAS), Dizziness Handicap Inventory (DHI), Activities-Specific Balance Confidence Scale (ABC) scores by the second follow-up (at 2nd week after treatment, P<0.05). However-improvement in the medication group occurred slightly later, DHI for 1 month and SAS for 2 months after treatment (P<0.05). Also, the improvement in the onset time of unilateral weakness (UW) at 2nd week after treatment in the personalized vestibular rehabilitation (PVR) group was faster than that in the medication group.

CONCLUSION
In general, the short-term PVR program showed great advantages by prompting vestibular compensation quickly and putting forward future direction for clinical treatment on decompensated vestibular vertigo.

Ding|Chen-Ru|CR| Gao|Ying-Qi|YQ| Zhou|Yu-Juan|YJ| Gu|Jun|J| Wang|Jing|J|

vestibular rehabilitation
vertigo
vestibular compensation
medication
personalized program
therapy


Inhibition of KCa2 Channels Decreased the Risk of Ventricular Arrhythmia in the Guinea Pig Heart During Induced Hypokalemia.

Abstract:
Background
Hypokalemia reduces the cardiac repolarization reserve. This prolongs the QT-interval and increases the risk of ventricular arrhythmia; a risk that is exacerbated by administration of classical class 3 anti-arrhythmic agents.Small conductance Ca2+-activated K+-channels (KCa2) are a promising new atrial selective target for treatment of atrial fibrillation. Under physiological conditions KCa2 plays a minor role in ventricular repolarization. However, this might change under hypokalemia because of concomitant increases in ventriculay -60r intracellur Ca2+.

Purpose
To study the effects of pharmacological KCa2 channel inhibition by the compounds AP14145, ICA, or AP30663 under hypokalemic conditions as compared to dofetilide and hypokalemia alone time-matched controls (TMC).

Methods
The current at +10 mV was compared in HEK293 cells stably expressing KCa2.3 perfused first with normo- and then hypokalemic solutions (4 mM K+ and 2.5 mM K+, respectively). Guinea pig hearts were isolated and perfused with normokalemic (4 mM K+) Krebs-Henseleit solution, followed by perfusion with drug or vehicle control. The perfusion was then changed to hypokalemic solution (2.5 mM K+) in presence of drug. 30 animals were randomly assigned to 5 groups: ICA, AP14145, AP30663, dofetilide, or TMC. QT-interval, the interval from the peak to the end of the T wave (Tp-Te), ventricular effective refractory period (VERP), arrhythmia score, and ventricular fibrillation (VF) incidence were recorded.

Results
Hypokalemia slightly increased KCa2.3 current compared to normokalemia. Application of KCa2 channel inhibitors and dofetilide prolonged the QT interval corrected for heart rate. Dofetilide, but none of the KCa2 channel inhibitors increased Tp-Te during hypokalemia. During hypokalemia 4/6 hearts in the TMC group developed VF (two spontaneously, two by S1S2 stimulation) whereas 5/6 hearts developed VF in the dofetilide group (two spontaneously, three by S1S2 stimulation). In comparison, 0/6, 1/6, and 1/6 hearts developed VF when treated with the KCa2 channel inhibitors AP30663, ICA, or AP14145, respectively.

Conclusion
Hypokalemia was associated with an increased incidence of VF, an effect that also seen in the presence of dofetilide. In comparison, the structurally and functionally different KCa2 channel inhibitors, ICA, AP14145, and AP30663 protected the heart from hypokalemia induced VF. These results support that KCa2 inhibition may be associated with a better safety and tolerability profile than dofetilide.

Diness|Jonas Goldin|JG|
Abildgaard|Lea|L|
Bomholtz|Sofia Hammami|SH|
Skarsfeldt|Mark Alexander|MA|
Edvardsson|Nils|N|
Sørensen|Ulrik S|US|
Grunnet|Morten|M|
Bentzen|Bo Hjorth|BH|

arrhythmia
hypokalemia
dofetilide
KCa2 channel inhibitor
Kv11.1 blockers
SK channel
SK channel inhibitor
antiarrhythmic drug


Matrix Metalloproteinase 3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease and Cell Differentiation.

Abstract: Cells must alter their expression profiles and morphological characteristics but also reshape the extracellular matrix (ECM) to fulfill their functions throughout their lifespan. Matrix metalloproteinase 3 (MMP-3) is a member of the matrix metalloproteinase (MMP) family, which can degrade multiple ECM components. MMP-3 can activate multiple pro-MMPs and thus initiates the MMP-mediated degradation reactions. In this review, we summarized the function of MMP-3 and discussed its effects on biological activities. From this point of view, we emphasized the positive and negative roles of MMP-3 in the pathogenesis of disease and cell differentiation, highlighting that MMP-3 is especially closely involved in the occurrence and development of osteoarthritis. Then, we discussed some pathways that were shown to regulate MMP-3. By writing this review, we hope to provide new topics of interest for researchers and attract more researchers to investigate MMP-3.

Wan|Jiangtao|J| Zhang|Guowei|G| Li|Xin|X| Qiu|Xianshuai|X| Ouyang|Jun|J| Dai|Jingxing|J| Min|Shaoxiong|S|

matrix metalloproteinase 3
cell differentiation
extracellular matrix
osteoarthritis
stem cells


Genotyping Echinococcus granulosus from Canine Isolates in Ilam Province, West of Iran.

Abstract:
Background
Cystic Echinococcosis (CE) is one of the most common parasitic zoonosis caused by Echinococcus granulosus worldwide. This study investigated genotype diversity of Echinococcus granulosus isolated from stray dogs and golden jackals in Ilam province, West of Iran.

Methods
Adult worms were collected from the small intestine of the stray dogs and golden jackals from Ilam Province roads during 2012-2014. DNA was extracted from the adult worms and the partial mitochondrial NADH dehydrogenase subunit1 (nad1) was amplified by PCR then the products were digested by using HpaII, Rsa1, and Alu1 restriction enzymes. In order to confirm RFLP results, a number of PCR products were bi-directionally sequenced.

Results
Totally, 20 stray dogs out of 75 (26.66%) and two out of 73 (2.74%) golden jackal showed infection with E. granulosus. Amplified PCR product for all isolates was a band of approximately 550bp. Alu1 digested the product into two bands of approximately 160bp and 390bp fragments, while the Rsa1 cut the product into 320bp and 230bp fragments and the HpaII had no effect on the PCR product for both dog and jackal samples. The isolate sequences of mtDNAnad1 gene indicated 100% homology with references G1, G2 and G3 sequences in the GenBank database.

Conclusion
The genotype of adult E. granulosus was similar to larval stage genotypes of parasite (G1-G3 complex).

Dalimi|Abdolhossein|A| Shamsi|Morteza|M| Khosravi|Afra|A| Ghaffarifar|Fatemeh|F|

Genotyping
Echinococcus granulosus
Iran
Stray dog
Golden jackal


Homology modeling and heterologous expression of highly alkaline subtilisin-like serine protease from Bacillus halodurans C-125.

Abstract: Here we report heterologous expression, enzymatic characterization and structure homology modeling of a subtilisin-like alkaline serine protease (ASP) from Bacillus halodurans C-125. Encoding gene was successfully obtained by PCR and cloned into pMA0911 shuttle vector under the control of strong HpaII promoter and expressed extracellularly. ASP enzyme was successfully expressed in B. subtilis WB800 cell line lacking eight extracellular proteases and produced extracellularly in the culture medium. Km, Vmax and specific activity parameters of the recombinantly produced ASP were identified as 0.2899 mg/ml, 76.12 U/ml and 9500 U/mg, respectively. The purified enzyme revealed remarkable proteolytic activity at highly alkaline conditions with a pH optimum 12.0 and notable thermostability with temperature optimum at 60 °C. Furthermore, substrate-free enzyme revealed remarkable pH stability at pH 12.0 and maintained 93% of its initial activity when incubated at 37 °C for 24 h and 60% of its initial activity upon incubation at 60 °C for 1 h. Theoretically calculated molecular mass of ASP protein was confirmed through SDS-PAGE and western blot analysis (Mw: 28.3 kDa). The secondary and tertiary structures of ASP protein were also identified through homology modeling and further examined in detail. ASP harbors a typical S8/S53 peptidase domain comprising 17 β-sheets and 9 α-helixes within its secondary structure. The structure dynamics analysis of modeled 3D structure further revealed that transient inactivating propeptide chain is the most dynamic region of ASP enzyme with 8.52 Å2 β-Factor value. Additional residue-dependent fluctuation plot analysis also confirmed the elevated structure dynamics patterning of ASP N-terminus which could be the potential prerequisite for the autonomous propeptide removal of alkaline serine peptidases. Yet the functional domain of ASP becomes quite stable after autonomous exclusion of its propeptide. Although the sequence homology between ASP and commercial detergent additive B. lentus protease (PDB ID:1GCI) was moderate (65.4% sequence similarity), their overlaid 3D structures revealed much higher similarity (98.14%) within 0.80 Å RMSD. In conclusions, with remarkable pH stability, notable thermostability and particularly high specific activity at extreme alkaline conditions, the unveiled ASP protein stands out as a novel protease candidate for various industrial sectors such as textile, detergent, leather, feed, waste, pharmaceutical and others.

D015964:Gene Expression Regulation, Bacterial

Subtilisin-like alkaline serine protease


AprilTag array-aided extrinsic calibration of camera-laser multi-sensor system.

Abstract: This paper presents a new algorithm for extrinsically calibrating a multi-sensor system including multiple cameras and a 2D laser scanner. On the basis of the camera pose estimation using AprilTag, we design an AprilTag array as the calibration target and employ a nonlinear optimization to calculate the single-camera extrinsic parameters when multiple tags are in the field of view of the camera. The extrinsic parameters of camera-camera and laser-camera are then calibrated, respectively. A global optimization is finally used to refine all the extrinsic parameters by minimizing a re-projection error. This algorithm is adapted to the extrinsic calibration of multiple cameras even if there is non-overlapping field of view. For algorithm validation, we have built a micro-aerial vehicle platform with multi-sensor system to collect real data, and the experiment results confirmed that the proposed algorithm yields great performance.

Tang|Dengqing|D| Hu|Tianjiang|T| Shen|Lincheng|L| Ma|Zhaowei|Z| Pan|Congyu|C|

Extrinsic calibration
Multi-sensor
AprilTag array
Non-overlapping


Unusual prenatal presentation of Rubinstein-Taybi syndrome: a case report.

Abstract: Rubinstein-Taybi syndrome (RTS) is a rare multiple congenital anomalies-intellectual disability syndrome. The diagnosis is made after birth and based on the detection of signs such as growth and developmental delay, minor facial anomalies, and broad thumbs and halluces. It is rare to suspect RTS during the prenatal period. We report here the approach to a patient with RTS whose pregnancy was complicated by multiple congenital anomalies. However, in the presence of the broad thumb and facial anomalies, we were able to suggest the correct diagnosis. The RTS was confirmed at birth and the molecular analysis of the major causative gene revealed a previously unreported heterozygous truncating mutation of CREBBP. This report provides new knowledge of the fetal phenotype of RTS.

Bedeschi|Maria Francesca|MF|
Crippa|Beatrice Letizia|BL|
Colombo|Lorenzo|L|
Guez|Sophie|S|
Cerruti|Marta|M|
Fogliani|Roberto|R|
Gervasini|Cristina|C|
Lalatta|Faustina|F|

Rubinstein-Taybi syndrome
RTS
CNS malformation
broad thumb-hallux
distinctive face
prenatal diagnosis


IMPDH2 promotes colorectal cancer progression through activation of the PI3K/AKT/mTOR and PI3K/AKT/FOXO1 signaling pathways.

Abstract:
BACKGROUND
Inosine 5'-monophosphate dehydrogenase type II (IMPDH2) was originally identified as an oncogene in several human cancers. However, the clinical significance and biological role of IMPDH2 remain poorly understood in colorectal cancer (CRC).

METHODS
Quantitative real-time polymerase chain reaction (qPCR), western blotting analysis, the Cancer Genome Atlas (TCGA) data mining and immunohistochemistry were employed to examine IMPDH2 expression in CRC cell lines and tissues. A series of in-vivo and in-vitro assays were performed to demonstrate the function of IMPDH2 and its possible mechanisms in CRC.

RESULTS
IMPDH2 was upregulated in CRC cells and tissues at both mRNA and protein level. High IMPDH2 expression was closely associated with T stage, lymph node state, distant metastasis, lymphovascular invasion and clinical stage, and significantly correlated with poor survival of CRC patients. Further study revealed that overexpression of IMPDH2 significantly promoted the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of CRC cells in vitro and accelerated xenograft tumour growth in nude mice. On the contrary, knockdown of IMPDH2 achieved the opposite effect. Gene set enrichment analysis (GSEA) showed that the gene set related to cell cycle was linked to upregulation of IMPDH2 expression. Our study verified that overexpressing IMPDH2 could promote G1/S phase cell cycle transition through activation of PI3K/AKT/mTOR and PI3K/AKT/FOXO1 pathways and facilitate cell invasion, migration and EMT by regulating PI3K/AKT/mTOR pathway.

CONCLUSIONS
These results suggest that IMPDH2 plays an important role in the development and progression of human CRC and may serve as a novel prognostic biomarker and therapeutic target for CRC.

Duan|Shiyu|S| Huang|Wenqing|W| Liu|Xiaoting|X| Liu|Xuming|X| Chen|Nana|N| Xu|Qiong|Q| Hu|Yukun|Y| Song|Wen|W| Zhou|Jun|J|

IMPDH2
Colorectal cancer
Proliferation
EMT
Cell cycle


Microbial Inoculants: Silver Bullet or Microbial Jurassic Park?

Abstract: The appeal of using microbial inoculants to mediate plant traits and productivity in managed ecosystems has increased over the past decade, because microbes represent an alternative to fertilizers, pesticides, and direct genetic modification of plants. Using microbes bypasses many societal and environmental concerns because microbial products are considered a more sustainable and benign technology. In our desire to harness the power of plant-microbial symbioses, are we ignoring the possibility of precipitating microbial invasions, potentially setting ourselves up for a microbial Jurassic Park? Here, we outline potential negative consequences of microbial invasions and describe a set of practices (Testing, Regulation, Engineering, and Eradication, TREE) based on the four stages of invasion to prevent microbial inoculants from becoming invasive. We aim to stimulate discussion about best practices to proactively prevent microbial invasions.

Jack|Chandra N|CN|
Petipas|Renee H|RH|
Cheeke|Tanya E|TE|
Rowland|Jennifer L|JL|
Friesen|Maren L|ML|

microbial invasion
agricultural sustainability
biostimulant
microbiome engineering
mycorrhizal fungi
rhizobia


Cellular projections from sensory hair cells form polarity-specific scaffolds during synaptogenesis.

Abstract: The assembly of a nervous system requires the extension of axons and dendrites to specific regions where they are matched with appropriate synaptic targets. Although the cues that guide long-range outgrowth have been characterized extensively, additional mechanisms are required to explain short-range guidance in neural development. Using a complementary combination of time-lapse imaging by fluorescence confocal microscopy and serial block-face electron microscopy, we identified a novel type of presynaptic projection that participates in the assembly of the vertebrate nervous system. Synapse formation by each hair cell of the zebrafish's lateral line occurs during a particular interval after the cell's birth. During the same period, projections emerge from the cellular soma, extending toward a specific subpopulation of mature hair cells and interacting with polarity-specific afferent nerve terminals. The terminals then extend along the projections to reach appropriately matched presynaptic sites, after which the projections recede. Our results suggest that presynaptic projections act as transient scaffolds for short-range partner matching, a mechanism that may occur elsewhere in the nervous system.

Dow|Eliot|E|
Siletti|Kimberly|K|
Hudspeth|Albert J|AJ|

zebrafish
lateral line
auditory system
filopodium
ribbon synapse
vestibular system


Branch-Selective Alkene Hydroarylation by Cooperative Destabilization: Iridium-Catalyzed ortho-Alkylation of Acetanilides.

Abstract: An iridium(I) catalyst system, modified with the wide-bite-angle and electron-deficient bisphosphine d(F) ppb (1,4-bis(di(pentafluorophenyl)phosphino)butane) promotes highly branch-selective hydroarylation reactions between diverse acetanilides and aryl- or alkyl-substituted alkenes. This provides direct and ortho-selective access to synthetically challenging anilines, and addresses long-standing issues associated with related Friedel-Crafts alkylations.

Crisenza|Giacomo E M|GE|
Sokolova|Olga O|OO|
Bower|John F|JF|

hydroarylation
acetanilides
branch selectivity
iridium
phosphine ligands


Responses of sea urchin larvae to field and laboratory acidification.

Abstract: Understanding the extent to which laboratory findings of low pH on marine organisms can be extrapolated to the natural environment is key toward making better projections about the impacts of global change on marine ecosystems. We simultaneously exposed larvae of the sea urchin Arbacia lixula to ocean acidification in laboratory and natural CO2 vents and assessed the arm growth response as a proxy of net calcification. Populations of embryos were simultaneously placed at both control and volcanic CO2 vent sites in Ischia (Italy), with a parallel group maintained in the laboratory in control and low pH treatments corresponding to the mean pH levels of the field sites. As expected, larvae grown at constant low pH (pHT 7.8) in the laboratory exhibited reduced arm growth, but counter to expectations, the larvae that developed at the low pH vent site (pHT 7.33-7.99) had the longest arms. The larvae at the control field site (pHT 7.87-7.99) grew at a similar rate to laboratory controls. Salinity, temperature, oxygen and flow regimes were comparable between control and vent sites; however, chlorophyll a levels and particulate organic carbon were higher at the vent site than at the control field site. This increased food availability may have modulated the effects of low pH, creating an opposite calcification response in the laboratory from that in the field. Divergent responses of the same larval populations developing in laboratory and field environments show the importance of considering larval phenotypic plasticity and the complex interactions among decreased pH, food availability and larval responses.

Foo|Shawna A|SA|
Koweek|David A|DA|
Munari|Marco|M|
Gambi|Maria Cristina|MC|
Byrne|Maria|M|
Caldeira|Ken|K|

Global change
Ocean acidification
Calcification
Carbon dioxide vents
Echinoplutei
Field experiments


An Examination of Health Inequities among College Students by Sexual Orientation Identity and Sex.

Abstract:
BACKGROUND
Lesbian, gay, and bisexual (LGB) college students may have an increased number of health inequities compared to their heterosexual counterparts. However, to date, no research has provided a comprehensive examination of health-related factors by sexual orientation identity and sex among a national sample of college students. Thus, the purpose of this study was to examine physical, sexual, interpersonal relations/safety, and mental health inequities by sexual orientation identity and sex among a national sample of college students.

DESIGN AND METHODS
Participants (n=39,767) completed the National College Health Assessment II during the fall 2008/spring 2009 academic year. Hierarchical binary logistic regression analyses were used to examine health inequities by sexual orientation identity and sex.

RESULTS
LGB students compared to heterosexual students, experienced multiple health inequities including higher rates of being verbally threatened and lower rates of physical activity and condom use.

CONCLUSIONS
An understanding of health inequities experienced by LGB college students is critical as during these years of transition, students engage in protective (e.g., physical activity) and risky (e.g., lack of condom use) health behaviours, establishing habits that could last a lifetime. Future research should be used to design and implement targeted public health strategies and policies to reduce health inequities and improve health-related quality of life among LGB college students. Significance for public healthHealth inequities based on sexual orientation identity and sex among college students is a critical public health concern. Based on the results of the current study, lesbian, gay, and bisexual (LGB) college students experienced multiple physical, sexual, interpersonal relations and safety, and mental health inequities. This understanding of health inequities experienced by LGB college students is critical as during these years of transition, students engage in protective (e.g., physical activity) and risky (e.g., lack of condom use) health behaviours, establishing habits that could last a lifetime. By intervening during the college years, targeted public health strategies and policies can be designed and implemented to reduce health inequities and improve health-related quality of life among LGB individuals during mid-to-later adulthood.

Brittain|Danielle R|DR|
Dinger|Mary K|MK|

health inequities
college students
lesbian
gay
bisexual
heterosexual


An observational study on the incidence of tuberculosis among a cohort of HIV infected adults in a setting with low prevalence of tuberculosis.

Abstract:
BACKGROUND
Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low TB burden where screening for latent TB infection is not routinely carried out.

METHODS
an observational cohort study on HIV-infected adults attending the HIV clinic at Queen Elizabeth Hospital Birmingham, UK between 1 January 2011 and 30 September 2015. Patients with culture-proven TB after HIV diagnosis, or those treated for clinical diagnosis of the infection, were classified as having "active TB".

RESULTS
1824 patients were included in the study (5347 patient years of follow up), of whom 21 patients developed TB (16 microbiology confirmed). Of the 666 new HIV diagnoses, six patients developed TB within one month, giving a TB prevalence at the time of HIV diagnosis of 0.9%. The total TB incidence for the remaining 1818 patients was 2.81 cases per 1000 patient years (95% CI: 1.63-4.53). TB incidence was significantly more common among patients with CD4 ≤ 200 cells/mm3 compared to those with CD4 > 500 cells/mm3 (28.2 vs. 1.22 per 1000 patient years, p < 0.001), and in patients with VL ≥ 40 copies/mL compared to <40 copies/mL (8.30 vs. 1.42, p < 0.001).

CONCLUSION
In settings with low TB prevalence, early start of combined antiretroviral therapy and intensified TB case finding protocols may significantly reduce the incidence of TB.

HIV
TB
incidence of TB
isoniazid prophylaxis


Influence of Vitamin C on Urine Dipstick Test Results.

Abstract:
BACKGROUND
Vitamin C is a strong reducing agent found at high levels in various foods, and it may influence the results of urine strip tests even at an ordinary consumption levels. After oral administration, we measured urine vitamin C levels using urine strips and evaluated whether vitamin C interfered with various test items. The utility of a urine strip with a vitamin C indicator was assessed.

METHODS
Thirty-three healthy volunteers each ingested 1,000 mg of vitamin C. Their urine samples were tested for vitamin C using a URiSCAN 11 strip (YD Diagnostics, Korea) before and after administration of vitamin C. Standard materials were added to normal pooled urine to generate urine samples with various concentrations of the analytes tested (blood, bilirubin, nitrite, leukocytes, and glucose), and vitamin C was spiked to predetermined levels. These samples were then tested using two urine strips - URiSCAN and Chemstrip test strip (Roche Diagnostics, Germany) - to evaluate interference from vitamin C. In clinical samples with positive vitamin C results, microscopic and chemical analyses were also conducted to examine the differences.

RESULTS
Thirteen urine samples from the 33 volunteers were positive for vitamin C before ingestion, and all subjects were positive after ingestion. Vitamin C spiking of urine demonstrated false-negative results at various concentrations. Of 159 specimens with positive results for vitamin C, 14 showed discrepant results after additional confirmatory tests.

CONCLUSIONS
Vitamin C in urine can cause significant interference with urine strip tests. A urine strip with a vitamin C indicator is useful to reduce the risk of incorrect results in regard to disease states.

Ko|Dae-Hyun|DH| Jeong|Tae-Dong|TD| Kim|Sollip|S| Chung|Hee-Jung|HJ| Lee|Woochang|W| Chun|Sail|S| Min|Won-Ki|WK|


OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels.

Abstract: Mechanically activated (MA) ion channels convert physical forces into electrical signals, and are essential for eukaryotic physiology. Despite their importance, few bona-fide MA channels have been described in plants and animals. Here, we show that various members of the OSCA and TMEM63 family of proteins from plants, flies, and mammals confer mechanosensitivity to naïve cells. We conclusively demonstrate that OSCA1.2, one of the Arabidopsis thaliana OSCA proteins, is an inherently mechanosensitive, pore-forming ion channel. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. Our findings will enable studies to gain deep insight into molecular mechanisms of MA channel gating, and will facilitate a better understanding of mechanosensory processes in vivo across plants and animals.

OSCA
mechanically activated
ion channels
<i>a. thaliana</i>
D. melanogaster
evolutionary biology
human
mechanotransduction
molecular biophysics
mouse
structural biology


Dynamic regulation of chromatin topology and transcription by inverted repeat-derived small RNAs in sunflower.

Abstract: Transposable elements (TEs) are extremely abundant in complex plant genomes. siRNAs of 24 nucleotides in length control transposon activity in a process that involves de novo methylation of targeted loci. Usually, these epigenetic modifications trigger nucleosome condensation and a permanent silencing of the affected loci. Here, we show that a TE-derived inverted repeat (IR) element, inserted near the sunflower HaWRKY6 locus, dynamically regulates the expression of the gene by altering chromatin topology. The transcripts of this IR element are processed into 24-nt siRNAs, triggering DNA methylation on its locus. These epigenetic marks stabilize the formation of tissue-specific loops in the chromatin. In leaves, an intragenic loop is formed, blocking HaWRKY6 transcription. While in cotyledons (Cots), formation of an alternative loop, encompassing the whole HaWRKY6 gene, enhances transcription of the gene. The formation of this loop changes the promoter directionality, reducing IR transcription, and ultimately releasing the loop. Our results provide evidence that TEs can act as active and dynamic regulatory elements within coding loci in a mechanism that combines RNA silencing, epigenetic modification, and chromatin remodeling machineries.

D042002:Chromatin Assembly and Disassembly

D012045:Regulatory Sequences, Nucleic Acid

small RNAs
sunflower
DNA methylation
chromatin loops


Safety evaluations of adalimumab for childhood chronic rheumatic diseases.

Abstract:
INTRODUCTION
Childhood rheumatic diseases (CRD) are chronic inflammatory conditions, often leading to severe functional impairment and disability. They produce high direct and indirect costs for patients, their families and society overall. Biologic treatment, adalimumab of note, has drastically changed the disease management, significantly decreasing morbidity, over childhood, and eventually lifelong. After 12 years of pediatric experience with adalimumab, safety data resulted of great interest.

AREAS COVERED
This review summarizes published knowledge about safety of adalimumab in clinical trials and real-life setting studies. Infections and site injection reactions are considered the most frequent adverse events, but the occurrence of second autoimmune diseases as well as malignancy development are the two major concerns of the medical community and families.

EXPERT OPINION
Adalimumab has revolutionized treatment and prognosis of most of CRD, resulting in good outcomes with highly acceptable safety profile. Number and type of entered adverse events differ from clinical trials and registries, these latter mirroring clinical real life. Different temporal observations and sample cohorts mainly account of this discrepancy. Both randomized clinical trials and real-world data are complementary. Clinical trials coupled with long-term registries will help to improve the evidence-based safety for children with CRD.

safety
Adalimumab
pediatric
adverse events
registry
children
JIA
TNFα
anti-TNFα
monoclonal antibody
rheumatologic
uveitis


Why do doctors seek peer support? A qualitative interview study.

Abstract:
OBJECTIVES
To understand how doctors reflect on when and why they seek help from an organised peer-support service.

DESIGN
Data were collected through audiotaped, qualitative, semi-structured interviews. The interviews were analysed with systematic text condensation.

SETTING
A peer-support service accessible to all doctors in Norway.

PARTICIPANTS
Thirteen doctors were interviewed after attending a counselling service in fall 2018. They were selected to represent variation in gender, demographics, and medical specialty. Doctors were excluded if the interview could not be held within 10 days after they had accessed peer support.

RESULTS
The doctors' perspectives and experiences of when and why they seek support and their expectations of the help they would receive are presented, and barriers to and facilitators of seeking support are discussed. Three categories of help-seeking behaviour were identified: (1) 'Concerned-looking for advice' describing help seeking in a strenuous situation with need for guidance; (2) 'Fear of not coping any longer' describing help seeking when struggling due to unreasonable stress and/or conflict in their lives; and (3) 'Looking for a way back or out' describing help seeking when out of work. Expectations to the help they would receive varied widely. Motivations for seeking help had more to do with factors enabling or restricting help-seeking than with the severity of symptoms.

CONCLUSIONS
Many different situations lead doctors to seek peer support, and they have various expectations of the service as well as diverse needs, motivations and constraints to seeking peer support. Further research is warranted to investigate the impact of peer support and how to tailor the service to best suit doctors' specific needs.

occupational & industrial medicine
preventive medicine
qualitative research


An experimental study comparing the respiratory effects of tapentadol and oxycodone in healthy volunteers.

Abstract:
Background
There is a clinical need for potent opioids that produce little or no respiratory depression. In the current study we compared the respiratory effects of tapentadol, a mu-opioid receptor agonist and noradrenaline reuptake inhibitor, and oxycodone, a selective mu-opioid receptor agonist. We hypothesize that tapentadol 100 mg has a lesser effect on the control of breathing than oxycodone 20 mg.

Methods
Fifteen healthy volunteers were randomized to receive oral tapentadol (100 and 150 mg), oxycodone 20 mg or placebo immediate release tablets in a crossover double-blind randomized design. The main end-point of the study was the effect of treatment on the ventilatory response to hypercapnia and ventilation at an extrapolated end-tidal PCO2 of 7.3 kPa (55 mmHg, VE55); VE55 was assessed prior and for 6-h following drug intake.

Results
All three treatments had typical opioid effects on the hypercapnic ventilatory response: a shift to the right coupled to a decrease of the response slope. Oxycodone 20 mg had a significantly larger respiratory depressant effect than tapentadol 100 mg (mean difference -5.0 L min-1, 95% confidence interval: -7.1 to -2.9 L min-1, P<0.01), but not larger than tapentadol 150 mg (oxycodone vs. tapentadol 150 mg: P>0.05).

Conclusions
In this exploratory study we observed that both tapentadol and oxycodone produce respiratory depression. Tapentadol 100 mg but not 150 mg had a modest respiratory advantage over oxycodone 20 mg. Further studies are needed to explore how these results translate to the clinical setting.

van der Schrier|R|R|
Jonkman|K|K|
van Velzen|M|M|
Olofsen|E|E|
Drewes|A M|AM|
Dahan|A|A|
Niesters|M|M|

opioids
respiratory depression
breathing
hypercapnic ventilatory response
opioid-induced respiratory depression


Preparation, surface functionalization and application of Fe3O4 magnetic nanoparticles.

Abstract: This paper reviews recent developments in the preparation, surface functionalization, and applications of Fe3O4 magnetic nanoparticles. Especially, it includes preparation methods (such as electrodeposition, polyol methods, etc.), organic materials (such as polymers, small molecules, surfactants, biomolecules, etc.) or inorganic materials (such as silica, metals, and metal oxidation/sulfide, functionalized coating of carbon surface, graphene, etc.) and its applications (such as magnetic separation, protein fixation, magnetic catalyst, environmental treatment, medical research, etc.). In the end, some existing challenges and possible future trends in the field were discussed.

Liu|Shixiang|S| Yu|Bing|B| Wang|Song|S| Shen|Youqing|Y| Cong|Hailin|H|

Preparation
Surface functionalization
Application
Magnetic nanoparticles
Environment treatment
Fe(3)O(4)
Medical science


Suppression of microRNA-96 expression inhibits the invasion of hepatocellular             carcinoma cells.

Abstract: MicroRNA-96 (miR-96) expression is dysregulated in certain types of cancers.             However, the role of miR-96 in hepatocellular carcinoma (HCC) invasion and metastasis             remains elusive. miR-96 expression was investigated in a number of HCC cell lines             by quantitative reverse transcription‑polymerase chain reaction (RT-PCR). Cell             invasive ability of metastatic HCCLM6 cells transfected with anti-miR-96 oligonucleotides             or miR-96 mimic was determined by Matrigel invasion assay in vitro. In addition,             metastasis-associated protein, osteopontin, was evaluated by Western blotting.             miR-96 expression was significantly increased in highly metastatic HCCLM6 cells.             Decreasing miR-96 expression with anti-miR-96 oligonucleotides led to reduced             migration and invasion of HCCLM6 cells in vitro. In particular, down-regulation             of miR-96 decreased osteopontin expression in HCCLM6 cells. Suppression of miR-96             expression inhibits the invasion of HCC cells, suggesting that miR-96 may be a             therapeutic target for inhibiting HCC invasion and metastasis.

Chen|Rong-Xin|RX| Xia|Yun-Hong|YH| Xue|Tong-Chun|TC| Ye|Sheng-Long|SL|

D015972:Gene Expression Regulation, Neoplastic

microRNA-96
hepatocellular carcinoma
osteopontin


A comprehensive analysis of the MAGE family as prognostic and diagnostic markers for hepatocellular carcinoma.

Abstract: The Melanoma Antigen Gene (MAGE) family is a large, highly conserved group of proteins which was reported to participate in the progression of multiple cancers in humans. However, the function of distinct MAGE genes in hepatocellular carcinoma (HCC) is largely unclear. In this study, we comprehensively evaluated the expression, clinical significance, genetic alteration, interaction network and functional enrichment of MAGEs in HCC. Our research showed that many MAGE genes were dysregulated in HCC. Among them, MAGEA1, MAGEC2, MAGED1, MAGED2, MAGEF1 and MAGEL2 were significantly associated with clinical stage and differentiation of HCC. MAGED1, MAGED2, MAGEA6, MAGEA12, MAGEA10, MAGEB4, MAGEL2 and MAGEC3 significantly correlated with HCC prognosis. Further functional enrichment analysis suggested the dysregulated MAGEs may play important roles in signal transduction. These results indicate that multiple dysregulated MAGEs might play important roles in the development of HCC and can be exploited as useful biomarkers for diagnosis and treatment in HCC.

Li|Rong|R| Gong|Jiao|J| Xiao|Cuicui|C| Zhu|Shuguang|S| Hu|Zhongying|Z| Liang|Jinliang|J| Li|Xuejiao|X| Yan|Xijing|X| Zhang|Xijian|X| Li|Danyang|D| Liu|Wei|W| Chong|Yutian|Y| Jie|Yusheng|Y|

MAGE family
Prognostic and diagnostic markers
Hepatocellular carcinoma


Social anhedonia, social networks, and psychotic-like experiences: A test of social deafferentation.

Abstract: Social connection is robustly associated with physical and mental health. So important is social connection that it features prominently in several etiological theories of serious psychopathology. Most notably, the social deafferentation hypothesis of schizophrenia posits that social anhedonia (SA) and isolation cause neural changes that produce psychosis. Here, we test several tenants of this theory by examining the relation between SA, psychotic-like experiences (PLE), and social networks. We find that SA and PLE are related to social networks, and that the relation between SA and PLE can be explained, in part, by the impact of SA on social networks.

Dodell-Feder|David|D| Shovestul|Bridget|B| Woodyatt|Jessica|J| Popov|Victoria|V| Germine|Laura|L|

Social networks
Social deafferentation
Schizophrenia


Determination of citrus juice coumarins, furanocoumarins and methoxylated flavones using solid phase extraction and HPLC with photodiode array and fluorescence detection.

Abstract: A synergistic combination of analytical techniques was developed for the simultaneous determination of the three most biologically active chemical families in citrus juices: methoxylated flavones, coumarins, and furanocoumarins. No rapid methodology has been available to determine them together. A solid phase extraction concentrated these groups and a ternary reverse phase HPLC gradient completely resolved them from other juice components. Two coumarins, isomeranzin and osthole, were identified in a sweet orange (C. sinensis) cultivar, Changyecheng, for the first time. Pummelo juice was characterized by coumarin and furanocoumarin epoxides such as meranzin and epoxybergamottin. No epoxides were observed in the more acidic juices. Added furanocoumarin epoxides hydrolyzed rapidly in the most acidic juices. The ratios of the UV peak areas at 320 nm to the fluorescence emission peaks as well as the ratio of fluorescence emission peaks at 450-400 nm could be used to identify chromatographic peaks.

Li|Gui-Jie|GJ|
Wu|Hou-Jiu|HJ|
Wang|Yu|Y|
Hung|Wei-Lun|WL|
Rouseff|Russell L|RL|

D002851:Chromatography, High Pressure Liquid

6′,7′-Dihydroxybergamottin (PubChem CID: 6440498)