Mechanisms of generation and exudation of Tibetan medicine Shilajit (Zhaxun).

Abstract:
Background
Shilajit is a commonly used Tibetan medicine, and its water extract is mainly used for various heat-related syndrome, especially that of stomach, liver and kidney. Shilajit is found to exudate from rocks of cliff at an altitude of 2000-4000 m as a water-soluble mixture of black paste and animal feces of Trodocterus spp. or Ochotona spp. Because it is difficult to reach the exudation points so as to explain the its formation process, the source of Shilajit still remains unclear and controversial, which severely impedes its safety and efficacy in clinical application.

Methods
In this work, a series of investigations as rock flakes identification, porosity determination, rock mineral analysis, scanning electron microscopy (SEM), and energy dispersive spectrometer (EDS) have been carried out to clarify the source of Shilajit, including the storage condition and exudation process of its organic matter, and to investigate the geological structure of the exudation points as well as physical and chemical characteristics of the mother rocks.

Results
The Shilajit exudation points were mainly distributed on the steep cliffs, where there were cavities and sections that could not be eroded by rainwater. The fundamental structure of the exudation points was determined by the rock's bedding planes, joints, fracture surfaces and faults, and developed into micro-topography later. The exudation points were distributed in the Triassic strata and scattered in the Early Mesozoic granitoids. The lithologic features were mainly slate, carbonaceous slate and sandy slate etc. The background rocks were characterized by intergranular pores, dissolved pore, joint and fracture development. Organic matter was widely distributed in these pores and fissures, which had condition for storage and exudation of organic matter.

Conclusions
Shilajit mainly distributed on sunny steep slopes and cliffs with a slope of 60° or above at altitude of 2000-4000 m. The lithology character of the Shilajit exudation area were mainly various metamorphic rocks of sedimentary rocks that were rich in organic carbon. The organic matter in Shilajit was found to flow out naturally from rocks along pore, structural plane and even accumulate on the surface of rock as a result of storage environment change caused by rock tectonic action.

Ding|Rong|R|0000-0002-1555-9523 Zhao|Mingming|M| Fan|Jiuyu|J| Hu|Xiuquan|X| Wang|Meng|M| Zhong|Shihong|S| Gu|Rui|R|

Shilajit
Formation process
Source
Geological environment
Rock identification


ALK Rearrangement-Positive Pancreatic Cancer with Brain Metastasis Has Remarkable Response to ALK Inhibitors: A Case Report.

Abstract: Patients with metastatic pancreatic cancer typically have poor prognosis due to the limited effectiveness of existing treatment options. ALK rearrangement-positive is rare in pancreatic cancer, but may occur in those with KRAS-wild type. We present a 34-year-old young man with ALK rearrangement-positive and KRAS-wild pancreatic cancer who had a remarkable response to crizotinib after resistance to prior chemotherapy and re-response to alectinib after brain metastases developed. This clinical observation suggests that comprehensive molecular profiling to guide targeted therapies is not only feasible, but also significantly improves survival outcomes for a subgroup of patients with pancreatic cancer.

Ou|Kai|K| Liu|Xiu|X| Li|Weihua|W| Yang|Yi|Y| Ying|Jianming|J| Yang|Lin|L|

pancreatic cancer
crizotinib
alectinib
brain metastases
ALK Kinase
EML4-ALK fusion protein


Cornstarch-based wound dressing incorporated with hyaluronic acid and propolis: In vitro and in vivo studies.

Abstract: The unique physicochemical and functional characteristics of starch-based biomaterials and wound dressings have been proposed for several biomedical applications. Film dressings of cornstarch/hyaluronic acid/ ethanolic extract of propolis (CS/HA/EEP) were prepared by solvent-casting and characterized by attenuated total reflectance/Fourier transform infrared spectroscopy, scanning electron microscopy, gas chromatography/mass spectrometry, light transmission, opacity measurements, EEP release, equilibrium swelling, and in vitro and in vivo evaluations. The CS/HA/0.5%EEP film dressing exhibited higher antibacterial activity against Staphylococcus aureus (2.08 ± 0.14 mm), Escherichia coli (2.64 ± 0.18 mm), and Staphylococcus epidermidis (1.02 ± 0.15 mm) in comparison with the CS, CS/HA, and CS/HA/0.25%EEP films. Also, it showed no cytotoxicity for the L929 fibroblast cells. This wound dressing could effectively accelerate the wound healing process at Wistar rats' skin excisions. These results indicate that enrichment of cornstarch wound dressings with HA and EEP can significantly enhance their potential efficacy as wound dressing material.

Eskandarinia|Asghar|A| Kefayat|Amirhosein|A| Rafienia|Mohammad|M| Agheb|Maria|M| Navid|Sepehr|S| Ebrahimpour|Karim|K|

Hyaluronic acid
Propolis
Cornstarch
Wound healing


Performance evaluation of non-thermal plasma injection for elemental mercury oxidation in a simulated flue gas.

Abstract: The use of non-thermal plasma (NTP) injection approach to oxidize elemental mercury (Hg(0)) in simulated flue gas at 110°C was studied, where a surface discharge plasma reactor (SDPR) inserted in the simulated flue duct was used to generate and inject active species into the flue gas. Approximately 81% of the Hg(0) was oxidized and 20.5μgkJ(-1) of energy yield was obtained at a rate of 3.9JL(-1). A maximal Hg(0) oxidation efficiency was found with a change in the NTP injection air flow rate. A high Hg(0) oxidation efficiency was observed in the mixed flue gas that included O2, H2O, SO2, NO and HCl. Chemical and physical processes (e.g., ozone, N2 metastable states and UV-light) were found to contribute to Hg(0) oxidation, with ozone playing a dominant role. The deposited mercury species on the internal surface of the flue duct was analyzed using X-ray photoelectron spectroscopy (XPS) and electronic probe microanalysis (EPMA), and the deposit was identified as HgO. The mercury species is thought to primarily exist in the form of HgO(s) by adhering to the suspended aerosols in the gas-phase.

An|Jiutao|J| Shang|Kefeng|K| Lu|Na|N| Jiang|Yuze|Y| Wang|Tiecheng|T| Li|Jie|J| Wu|Yan|Y|

D052918:Environmental Restoration and Remediation

Non-thermal plasma injection
Mercury oxidation
Surface discharge plasma reactor
HgO


Regulation of sexual odor preference by sex steroids in the posterodorsal medial amygdala in female rats.

Abstract: Our previous study in male rats demonstrated that bilateral administration of flutamide, an androgen receptor (AR) antagonist, into the posterodorsal medial amygdala (MePD) increased the time sniffing male odors to as high as that sniffing estrous odors, eliminating the preference for estrous odors over male odors. This made us speculate that under blockade of AR in the MePD, testosterone-derived estrogen acting on the same brain region arouses interest in male odors which is otherwise suppressed by concomitant action of androgen. In cyclic female rats, endogenous androgen has been thought to be involved in inhibitory regulation of estrogen-activated sexual behavior. Thus, in the present study, we investigated the possibility that in female rats the arousal of interest in male odors is also normally regulated by both estrogen and androgen acting on the MePD, as predicted by our previous study in male rats. Implantation of either the estrogen receptor blocker tamoxifen (TX) or a non-aromatizable androgen 5α-dihydrotestosterone (DHT) into the MePD of ovariectomized, estrogen-primed female rats eliminated preference for male odors over estrous odors by significantly decreasing the time sniffing male odors to as low as that sniffing estrous odors. The subsequent odor discrimination tests confirmed that the DHT and TX administration did not impair the ability to discriminate between male and estrous odors. These results suggest that in estrous female rats estrogen action in the MePD plays critical roles in the expression of the preference for male odors while androgen action in the same brain region interferes with the estrogen action.

Sexual odor preference
Amygdala
Female rats
Androgen
Estrogen


Synthesis of Secondary and Tertiary Alkyl Boronic Esters by gem-Carboborylation: Carbonyl Compounds as Bis(electrophile) Equivalents.

Abstract: An unprecedent gem-carboborylation of aldehydes and ketones provides access to various secondary and tertiary alkyl boronic esters. The addition of B2 pin2 to a carbonyl compound generates α-oxyl-substituted alkyl boron species. Organolithium and Grignard reagents are then applied as C nucleophiles for the 1,2-metalate rearrangement process. The organolithium reagents can also be generated by C-H lithiation or halogen/lithium exchange. The use of chiral ligands led to the generation of chiral alkyl boronic esters in enantioenriched form, demonstrating that the enantioselectivity of this transformation is catalyst-controlled.

alkyl boronic esters
boron
asymmetric catalysis
carboborylation
copper catalysis


Transcranial magnetic stimulation with acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide in healthy Beagle dogs.

Abstract: The aim of this study was to evaluate the influence of two sedation protocols on transcranial magnetic motor evoked potentials (TMMEPs) after transcranial magnetic stimulation in medium sized dogs. Onset latencies and peak-to-peak amplitudes, elicited in the extensor carpi radialis and cranial tibial muscles, were analysed in 10 healthy Beagles that received either acepromazine or dexmedetomidine in combination with levomethadone/fenpipramide, in a crossover design. Similar TMMEP recordings could be made using both sedation protocols at 80-90% stimulation intensity; however, there were significantly shorter onset latencies with the acepromazine-levomethadone/fenpipramide protocol at 100% stimulation intensity. Reference values were established and it was concluded that both drug combinations are feasible for measuring TMMEPs in medium sized dogs.

Amendt|H-L|HL|
Siedenburg|J S|JS|
Steffensen|N|N|
Söbbeler|F J|FJ|
Schütter|A|A|
Tünsmeyer|J|J|
Rohn|K|K|
Kästner|S B R|SB|
Tipold|A|A|
Stein|V M|VM|

Transcranial magnetic stimulation
Acepromazine
Dexmedetomidine
Magnetic motor evoked potentials
Canine


Nonlinear response characteristics of neural networks and single neurons undergoing optogenetic excitation.

Abstract: Optogenetic stimulation has become the method of choice for investigating neural computation in populations of neurons. Optogenetic experiments often aim to elicit a network response by stimulating specific groups of neurons. However, this is complicated by the fact that optogenetic stimulation is nonlinear, more light does not always equal to more spikes, and neurons that are not directly but indirectly stimulated could have a major impact on how networks respond to optogenetic stimulation. To clarify how optogenetic excitation of some neurons alters the network dynamics, we studied the temporal and spatial response of individual neurons and recurrent neural networks. In individual neurons, we find that neurons show a monotonic, saturating rate response to increasing light intensity and a nonmonotonic rate response to increasing pulse frequency. At the network level, we find that Gaussian light beams elicit spatial firing rate responses that are substantially broader than the stimulus profile. In summary, our analysis and our network simulation code allow us to predict the outcome of an optogenetic experiment and to assess whether the observed effects can be attributed to direct or indirect stimulation of neurons.

Nonlinear response characteristics
Neural networks
Optogenetics
Channelrhodopsin


A Systematic Review on the Use of Wearable Body Sensors for Health Monitoring: A Qualitative Synthesis.

Abstract: The use of wearable body sensors for health monitoring is a quickly growing field with the potential of offering a reliable means for clinical and remote health management. This includes both real-time monitoring and health trend monitoring with the aim to detect/predict health deterioration and also to act as a prevention tool. The aim of this systematic review was to provide a qualitative synthesis of studies using wearable body sensors for health monitoring. The synthesis and analysis have pointed out a number of shortcomings in prior research. Major shortcomings are demonstrated by the majority of the studies adopting an observational research design, too small sample sizes, poorly presented, and/or non-representative participant demographics (i.e., age, gender, patient/healthy). These aspects need to be considered in future research work.

wearable body sensors
health monitoring
qualitative synthesis
remote health management
IoT
physical activity monitoring
research shortcomings
sensor systems
user demography


The value of 3D images in the aesthetic evaluation of breast cancer conservative treatment. Results from a prospective multicentric clinical trial.

Abstract:
PURPOSE
BCCT.core (Breast Cancer Conservative Treatment. cosmetic results) is a software created for the objective evaluation of aesthetic result of breast cancer conservative treatment using a single patient frontal photography. The lack of volume information has been one criticism, as the use of 3D information might improve accuracy in aesthetic evaluation. In this study, we have evaluated the added value of 3D information to two methods of aesthetic evaluation: a panel of experts; and an augmented version of the computational model - BCCT.core3d.

MATERIAL AND METHODS
Within the scope of EU Seventh Framework Programme Project PICTURE, 2D and 3D images from 106 patients from three clinical centres were evaluated by a panel of 17 experts and the BCCT.core. Agreement between all methods was calculated using the kappa (K) and weighted kappa (wK) statistics.

RESULTS
Subjective agreement between 2D and 3D individual evaluation was fair to moderate. The agreement between the expert classification and the BCCT.core software with both 2D and 3D features was also fair to moderate.

CONCLUSIONS
The inclusion of 3D images did not add significant information to the aesthetic evaluation either by the panel or the software. Evaluation of aesthetic outcome can be performed using of the BCCT.core software, with a single frontal image.

Cardoso|Maria João|MJ|
Vrieling|Conny|C|
Cardoso|Jaime S|JS|
Oliveira|Helder P|HP|
Williams|Norman R|NR|
Dixon|J M|JM|
|||
|||

3D
Breast cancer conservative treatment
Software
Objective evaluation
Aesthetic results
2D
Delphi
Expert observers


A pragmatic regulatory approach for complex generics through the U.S. FDA 505(j) or 505(b)(2) approval pathways.

Abstract: The diverse nature of complex drug products poses challenges for the development of regulatory guidelines for generic versions. While complexity is not new in medicines, the technical capacity to measure and analyze data has increased. This requires a determination of which measurements and studies are relevant to demonstrate therapeutic equivalence. This paper describes the views of the NBCD Working Group and provides pragmatic solutions for approving complex generics by making best use of existing U.S. Food and Drug Administration's abbreviated approval pathways 505(j) and 505(b)(2). We argue that decisions on the appropriateness of submitting a 505(j) or 505(b)(2) application can build on the FDA's complex drug product classification as well as the FDA's much applauded guidance document for determining whether to submit an ANDA or a 505(b)(2) application. We hope that this paper contributes to the discussions to increase the clarity of regulatory approaches for complex generics, as well as the predictability for complex generic drug developers, to facilitate access to much-needed complex generics and to promote the sustainability of the healthcare system.

Klein|Kevin|K|
Borchard|Gerrit|G|
Shah|Vinod P|VP|
Flühmann|Beat|B|
McNeil|Scott E|SE|
de Vlieger|Jon S B|JSB|

generics
FDA
complex drugs
complex generic drug products
follow-on products
nonbiological complex drugs


Pneumothorax-associated fibroblastic lesion in combination with localized pleural angiomatosis: A possible cause of juvenile spontaneous hemopneumothorax.

Abstract: Spontaneous hemopneumothorax is an uncommon but potentially life-threatening condition, with a potential for a rapid ventilatory collapse and a large collection of hidden blood loss into the pleural cavity. Here, we report the first case in the literature on pneumothorax-associated fibroblastic lesion in combination with localized pleural angiomatosis in a 19-year-old Caucasian male, resulting in massive spontaneous hemopneumothorax and hypovolemic shock. Our findings support a causal link between this condition and pneumothorax. The possible superimposed hemothorax is explainable by the pleural involvement of large angiomatous vessels, prone to rupture.

Roncati|Luca|L| Pusiol|Teresa|T| Piscioli|Francesco|F| Scialpi|Michele|M| Barbolini|Giuseppe|G| Maiorana|Antonio|A|

Pneumothorax-associated fibroblastic lesion (PAFL)


European Society for Immunodeficiencies (ESID) and European Reference Network on Rare Primary Immunodeficiency, Autoinflammatory and Autoimmune Diseases (ERN RITA) Complement Guideline: Deficiencies, Diagnosis, and Management.

Abstract: This guideline aims to describe the complement system and the functions of the constituent pathways, with particular focus on primary immunodeficiencies (PIDs) and their diagnosis and management. The complement system is a crucial part of the innate immune system, with multiple membrane-bound and soluble components. There are three distinct enzymatic cascade pathways within the complement system, the classical, alternative and lectin pathways, which converge with the cleavage of central C3. Complement deficiencies account for ~5% of PIDs. The clinical consequences of inherited defects in the complement system are protean and include increased susceptibility to infection, autoimmune diseases (e.g., systemic lupus erythematosus), age-related macular degeneration, renal disorders (e.g., atypical hemolytic uremic syndrome) and angioedema. Modern complement analysis allows an in-depth insight into the functional and molecular basis of nearly all complement deficiencies. However, therapeutic options remain relatively limited for the majority of complement deficiencies with the exception of hereditary angioedema and inhibition of an overactivated complement system in regulation defects. Current management strategies for complement disorders associated with infection include education, family testing, vaccinations, antibiotics and emergency planning.

Brodszki|Nicholas|N|
Frazer-Abel|Ashley|A|
Grumach|Anete S|AS|
Kirschfink|Michael|M|
Litzman|Jiri|J|
Perez|Elena|E|
Seppänen|Mikko R J|MRJ|
Sullivan|Kathleen E|KE|
Jolles|Stephen|S|0000-0002-7394-6804

Complement
complement deficiencies
alternative pathway
classical pathway
mannan-binding lectin


Autoimmune disorders are common in myelodysplastic syndrome patients and confer an adverse impact on outcomes.

Abstract: The coexistence of autoimmune disorders (AD) in patients with myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) has been widely recognized, although with distinct results regarding their prevalence and impact on the outcomes of the underlying hematological process. This study was aimed to analyze the prevalence, clinical characteristics, and outcomes of MDS with AD in a series of 142 patients diagnosed with MDS and CMML. AD was ascertained by both the presence of clinical symptoms or compatible serological tests. In total, 48% patients were diagnosed as having AD, being hypothyroidism the most commonly reported clinical AD (8%) and antinuclear antibodies the most frequent serological parameter identified (23.2%). The presence of AD was associated with female gender, lower hemoglobin levels, and higher IPSS-R. Overall survival for patients with AD was inferior to those with no AD (69 vs. 88% at 30 months; HR 2.75, P = 0.008). Notably, clinical but not isolated immune serological parameters had an impact on the outcomes of patients with AD. Finally, in a multivariate analysis, the presence of AD (HR 2.26) along with disease risk categories (very low and low vs. intermediate, high, and very high IPSS-R; HR 4.62) retained their independent prognostic value (P < 0.001). In conclusion, AD are prevalent in MDS and CMML patients and have prognostic implications, especially in lower-risk MDS patients.

Montoro|Julia|J| Gallur|Laura|L| Merchán|Brayan|B| Molero|Antonieta|A| Roldán|Elisa|E| Martínez-Valle|Ferrán|F| Villacampa|Guillermo|G| Navarrete|Mayda|M| Ortega|Margarita|M| Castellví|Josep|J| Saumell|Silvia|S| Bobillo|Sabela|S| Bosch|Francesc|F| Valcárcel|David|D|

Autoimmune disorders
Myelodysplastic syndrome
Chronic myelomonocytic leukemia
Immune dysregulation


Deletion of conserved protein phosphatases reverses defects associated with mitochondrial DNA damage in Saccharomyces cerevisiae.

Abstract: Mitochondrial biogenesis is regulated by signaling pathways sensitive to extracellular conditions and to the internal environment of the cell. Therefore, treatments for disease caused by mutation of mtDNA may emerge from studies of how signal transduction pathways command mitochondrial function. We have examined the role of phosphatases under the control of the conserved α4/Tap42 protein in cells lacking a mitochondrial genome. We found that deletion of protein phosphatase 2A (PP2A) or of protein phosphatase 6 (PP6) protects cells from the reduced proliferation, mitochondrial protein import defects, lower mitochondrial electrochemical potential, and nuclear transcriptional response associated with mtDNA damage. Moreover, PP2A or PP6 deletion allows viability of a sensitized yeast strain after mtDNA loss. Interestingly, the Saccharomyces cerevisiae ortholog of the mammalian AMP-activated protein kinase was required for the full benefits of PP6 deletion and also for proliferation of otherwise wild-type cells lacking mtDNA. Our work highlights the important role that nutrient-responsive signaling pathways can play in determining the response to mitochondrial dysfunction.

Garipler|Görkem|G|
Mutlu|Nebibe|N|
Lack|Nathan A|NA|
Dunn|Cory D|CD|

D004249:DNA Damage
D004272:DNA, Mitochondrial
D005434:Flow Cytometry
D009154:Mutation
D010749:Phosphoprotein Phosphatases
D012441:Saccharomyces cerevisiae
D017384:Sequence Deletion
D059467:Transcriptome

TOR
bioenergetics
mitochondria
nutrient signaling
petite-negative


Injection laryngoplasty outcomes in irradiated and nonirradiated unilateral vocal fold paralysis.

Abstract:
OBJECTIVES/HYPOTHESIS
To evaluate the effect of radiation therapy on voice outcome and duration of effect of calcium hydroxylapatite (CaHA) injection laryngoplasty in unilateral vocal fold paralysis (UVFP) patients.

STUDY DESIGN
Retrospective case series.

METHODS
UVFP patients treated with CaHA injection laryngoplasty at the University of California San Francisco Voice and Swallowing Center were identified. Demographic information, history of irradiation to the larynx, and time to additional medialization procedures were obtained. Examinations at presentation and follow-up were analyzed for laryngostroboscopic parameters and CAPE-V scores.

RESULTS
Four nonirradiated and five irradiated patients underwent a total of six and nine injection laryngoplasties, respectively. Time to additional procedures was longer in irradiated patients (P = 0.02). Prior to injection, nonirradiated patients had more severe glottic insufficiency (P = 0.007, 0.002) than did irradiated patients. Postinjection, irradiated patients demonstrated improvement in overall voice quality, breathiness, and loudness, while nonirradiated patients demonstrated improved overall quality, breathiness, pitch, and loudness. Voice quality was not statistically different between patient groups.

CONCLUSION
CaHA injection laryngoplasty improved voice quality in both irradiated and nonirradiated patients. Nonirradiated patients experience greater vocal improvement compared to irradiated patients. Vocal cord stiffness due to radiation-induced changes may be responsible for the lack of improvement in pitch. Time to additional procedures was longer in irradiated patients and may be secondary to effects of prior radiation on graft resorption. Vocal fold medialization with CaHA injection remains a safe and efficacious treatment for UVFP in both irradiated and nonirradiated patients.

Chang|Joseph|J|
Courey|Mark S|MS|
Al-Jurf|Soha A|SA|
Schneider|Sarah L|SL|
Yung|Katherine C|KC|

Laryngoplasty
unilateral vocal fold paralysis
radiation
voice
calcium hydroxylapatite
glottic insufficiency
vocal fold injection


Profiling the Clostridia with butyrate-producing potential in the mud of Chinese liquor fermentation cellar.

Abstract: Butyrate and its derivates pertain to the key aroma contributors of strong-flavour baijiu, a kind of Chinese liquors, that is produced from grains by solid-state multispecies anaerobic fermentation in a mud cellar. Microbes inhabiting in the fermentation pit mud largely determines baijiu's flavour and quality. In order to shed light on the microbial functional groups driving butyrate production in pit mud, clone library analysis was firstly performed and the results demonstrated that Clostridia (relative abundance: 50%) and Bacilli (37%) were major groups possessing butyrate kinase (buk) pathway and Clostridia (98%) dominated butyryl-CoA:acetate CoA-transferase (but) pathway. According to Clostridial specific-16S rRNA gene sequencing analysis, we found the resilience character of Clostridial community in pit mud. Amongst Clostridial groups, 32.0% of the sequences were grouped into Clostridiales incertae sedis, followed by Heliobacteriaceae (18.3%) and Clostridiaceae 1 (8.4%). Moreover, Hydrogenispora, Sedimentibacter and Clostridium were the top three abundant genera. Relative abundance of Hydrogenispora was higher in the late days of fermentation, while Sedimentibacter exhibited higher proportion in the early days. Different from the previous studies using universal bacterial primer sets, Hydrogenispora was first reported as one dominant genus in pit mud. As for the reported potential butyrate producer Clostridium, nineteen species were obtained and ten of them were first isolated from the pit mud. Amongst them, buk was identified in eleven species by PCR analysis, while but was identified in the other seven, indicating the species-specific butyrate synthesis pathways of Clostridium. This study provides a perspective on targeting and isolating specific functional microbes in baijiu microbiota with the gene sequence-based medium prediction method.

Chai|Li-Juan|LJ| Xu|Peng-Xiang|PX| Qian|Wei|W| Zhang|Xiao-Juan|XJ| Ma|Jian|J| Lu|Zhen-Ming|ZM| Wang|Song-Tao|ST| Shen|Cai-Hong|CH| Shi|Jin-Song|JS| Xu|Zheng-Hong|ZH|

Strong-flavour baijiu
Fermentation pit mud
Butyric acid
Clostridial community structure
Clostridium isolation


The glucocorticoid receptor specific modulator CORT108297 reduces brain pathology following status epilepticus.

Abstract:
OBJECTIVE
Glucocorticoid levels rise rapidly following status epilepticus and remain elevated for weeks after the injury. To determine whether glucocorticoid receptor activation contributes to the pathological sequelae of status epilepticus, mice were treated with a novel glucocorticoid receptor modulator, C108297.

METHODS
Mice were treated with either C108297 or vehicle for 10 days beginning one day after pilocarpine-induced status epilepticus. Baseline and stress-induced glucocorticoid secretion were assessed to determine whether hypothalamic-pituitary-adrenal axis hyperreactivity could be controlled. Status epilepticus-induced pathology was assessed by quantifying ectopic hippocampal granule cell density, microglial density, astrocyte density and mossy cell loss. Neuronal network function was examined indirectly by determining the density of Fos immunoreactive neurons following restraint stress.

RESULTS
Treatment with C108297 attenuated corticosterone hypersecretion after status epilepticus. Treatment also decreased the density of hilar ectopic granule cells and reduced microglial proliferation. Mossy cell loss, on the other hand, was not prevented in treated mice. C108297 altered the cellular distribution of Fos protein but did not restore the normal pattern of expression.

INTERPRETATION
Results demonstrate that baseline corticosterone levels can be normalized with C108297, and implicate glucocorticoid signaling in the development of structural changes following status epilepticus. These findings support the further development of glucocorticoid receptor modulators as novel therapeutics for the prevention of brain pathology following status epilepticus.

Wulsin|Aynara C|AC|
Kraus|Kimberly L|KL|
Gaitonde|Kevin D|KD|
Suru|Venkat|V|
Arafa|Salwa R|SR|
Packard|Benjamin A|BA|
Herman|James P|JP|
Danzer|Steve C|SC|

D006576:Heterocyclic Compounds, 4 or More Rings

Glucocorticoid receptor
Status epilepticus
Hypothalamic-pituitary-adrenal axis
Corticosterone (CORT)
Epilepsy
Pharmacological therapy
Seizures


National Influenza Surveillance in the Philippines from 2006 to 2012: seasonality and circulating strains.

Abstract:
BACKGROUND
The results of routine influenza surveillance in 13 regions in the Philippines from 2006 to 2012 are presented, describing the annual seasonal epidemics of confirmed influenza virus infection, seasonal and alert thresholds, epidemic curve, and circulating influenza strains.

METHODS
Retrospective analysis of Philippine influenza surveillance data from 2006 to 2012 was conducted to determine seasonality with the use of weekly influenza positivity rates and calculating epidemic curves and seasonal and alert thresholds using the World Health Organization (WHO) global epidemiological surveillance standards for influenza.

RESULTS
Increased weekly influenza positive rates were observed from June to November, coinciding with the rainy season and school opening. Two or more peaks of influenza activity were observed with different dominant influenza types associated with each peak. A-H1N1, A-H3N2, and two types of B viruses circulated during the influenza season in varying proportions every year. Increased influenza activity for 2012 occurred 8 weeks late in week 29, rather than the expected week of rise of cases in week 21 as depicted in the established average epidemic curve and seasonal threshold. The intensity was severe going above the alert threshold but of short duration. Southern Hemisphere vaccine strains matched circulating influenza virus for more surveillance years than Northern Hemisphere vaccine strains.

CONCLUSIONS
Influenza seasonality in the Philippines is from June to November. The ideal time to administer Southern Hemisphere influenza vaccine should be from April to May. With two lineages of influenza B circulating annually, quadrivalent vaccine might have more impact on influenza control than trivalent vaccine. Establishment of thresholds and average epidemic curve provide a tool for policy-makers to assess the intensity or severity of the current influenza epidemic even early in its course, to help plan more precisely resources necessary to control the outbreak. Influenza surveillance activities should be continued in the Philippines and funding for such activities should already be incorporated into the Philippine health budget.

Lucero|Marilla G|MG|
Inobaya|Marianette T|MT|
Nillos|Leilani T|LT|
Tan|Alvin G|AG|
Arguelles|Vina Lea F|VL|
Dureza|Christine Joy C|CJ|
Mercado|Edelwisa S|ES|
Bautista|Analisa N|AN|
Tallo|Veronica L|VL|
Barrientos|Agnes V|AV|
Rodriguez|Tomas|T|
Olveda|Remigio M|RM|

Alert threshold
Circulating influenza strains
Influenza seasonality
Average epidemic curve
Seasonal threshold
Influenza vaccine strains


Cost-Benefit Analysis of Allowing Additional Time in Cleaning Hospital Contact Precautions Rooms.

Abstract: Increasing cleaning time may reduce hospital-acquired transmission of Clostridioides difficile, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococcus (VRE). We constructed a cost-benefit model to estimate the impact of implementing an enhanced cleaning protocol, allowing hospital housekeepers an additional 15 minutes to terminally clean contact precautions rooms. The enhanced cleaning protocol saved the hospital $758 per terminally-cleaned room when accounting for only C. difficile. Scaling up to a hospital with 100 cases of C. difficile/year, and the US annual C. difficile incidence, cost savings were $75,832/year and $169.8 million/year, respectively. These results may inform infection control strategic decision-making and resource allocation.

implementation
enhanced cleaning
infection control
Cost benefit analysis
healthcare acquired infections


Ring chromosome 7 in a child with T-cell acute lymphoblastic leukemia with myeloid markers.

Abstract: Ring chromosomes are uncommon in hematological diseases. Here we present the case of a 13-year-old girl with leukocytosis, anemia, and lymphadenopathy. Flow cytometry analysis revealed a predominant precursor T lymphoid population expressing CD7, CD5, CD2, and cytoplasmic CD3 with partial expression of CD33, CD34, CD117, and CD11c; TdT was positive, and myeloperoxidase was negative. The bone marrow aspirate showed markedly increased blasts that were positive for CD3, CD7, CD34, TdT, and myeloperoxidase (rare positivity) by immunohistochemistry stain, consistent with T-cell acute lymphoblastic leukemia (T-ALL) extensively involving a hypercellular marrow for age. The karyotype showed a ring 7 in 12 of the 21 metaphase cells examined and deletions of the subtelomeric regions on chromosome 7. Deletions in the short arm of chromosome 7 and the long arm of chromosome 7 are present in 2% to 4% of pediatric T-ALL cases. Ring chromosome 7 is typically seen in myeloid malignancies, including acute myeloid leukemia.

ring chromosome 7
T-cell acute lymphoblastic leukemia
Myeloid markers
pediatric


Longitudinal uncoupling of the heart and arteries with aging in a community-dwelling population.

Abstract: Although mechanical energy transfer between the heart and arterial system, referred to as arterial-ventricular (AV) coupling, is an important determinant of cardiovascular performance, how AV coupling changes over time within and among individuals as they age has not been fully explored. We studied 129 participants (baseline age 21-96) of the Baltimore Longitudinal Study of Aging, free of clinical CVD. Participants underwent repeated multigated cardiac blood pool scans to estimate left ventricular (LV) volumes (SV, EDV, and ESV). Total systemic vascular resistance (TSVR), total arterial compliance (TAC), effective arterial elastance (Ea), and end-systolic LV elastance (Elv) were calculated using LV volumes and brachial BP measurements; calculated Ea/Elv was the measure of AV coupling. Linear mixed-effects models were used to estimate person-specific rates of change (Change) for each variable. The rate at which Ea increased over time was faster than the rate at which Elv increased, resulting in AV uncoupling (increased Ea/Elv) over time that was significantly greater in women than in men. Loss of arterial compliance was the main determinant of (Ea/Elv)Change, which was negatively associated with changes in SV and EDV but positively with changes in ESV. Progressive AV uncoupling occurred with aging and was more pronounced in women than men. While Ea change did not differ by sex, Elv increased at a slower rate in women than in men. AV uncoupling was inversely associated with EDV and SV rates of change and a directly associated with an increase in ESV rate of change. Additional studies are needed to explore the functional consequences of AV uncoupling in healthy individuals with respect to the emergence of age-associated clinical cardiovascular diseases, such as heart failure with preserved ejection fraction.

AlGhatrif|Majd|M|0000-0002-7642-2643
Morrell|Chris H|CH|
Becker|Lewis C|LC|
Chantler|Paul D|PD|
Najjar|Samer S|SS|
Ferrucci|Luigi|L|
Gerstenblith|Gary|G|
Lakatta|Edward G|EG|

Person-specific arterial ventricular coupling


Lethal pulmonary thromboembolism: an autopsy-based study on a rare but legally relevant event.

Abstract:
CONTEXT
Pulmonary thromboembolism (PTE) is the severe end stage of many different diseases producing prolonged patient immobilization or a hypercoagulative state. Lethal PTE is also one of the most frequent topics for suspected medical malpractice, especially when dealing with patients originally affected by non-critical illnesses and suddenly killed by a non-prevented embolic event. The crucial forensic question about a lethal PTE is the following one: was this lethal PTE an unpreventable complication or was it a consequence of real medical malpractice?

MATERIALS AND METHODS
The authors analyzed the 1999-2009 autopsy archive of the Institute of Forensic Medicine of Milan University and selected all the cases where PTE was the cause of death. For every selected case, the authors also collected all the available demographic and clinical data. Statistical analysis was performed using SPSS V.16.00.

RESULTS
In the period 1999-2009, 129 (1.25%) cases out of a total of 10,288 autopsies were diagnosed as having suffered lethal PTE. The male to female ratio was 1:2 (34.1% versus 65.9%). The mean age at death was 67 ± 18 years. In 41% of cases the death occurred outside of the hospital and in the absence of any medical support; in 36.5% of cases it occurred during the territorial paramedical support or during the very first evaluation in the emergency; and in the remaining 22.5% of cases it occurred during a period of hospitalization. In 33.4% of the selected cases, a typical preliminary event was positively identified: a pure major trauma (18.6%); a trauma followed by a major surgery (7%); a major non post-traumatic surgery (7%); and a non-surgical delivery. Symptoms suggesting PTE were detected in 46 cases (35.7%). Nine cases underwent a judicial autopsy in the same original hypothesis of a medical malpractice for incorrect prophylaxis in acutely bed-restricted patients.

CONCLUSIONS
Post-surgical PTE cannot be automatically labeled a consequence of medical malpractice. The combination of correct prophylaxis, careful diagnostic monitoring of the high-risk patient and the correct therapy surely reduces the occurrence of lethal PTE, but it does not completely erase such an insidious pathology. In the hypothesis of a causative medical malpractice, only careful analysis by an experienced forensic pathologist can make a reliable distinction between an unpreventable complication and real medical malpractice.

Mobilia|Francesca|F|
Casali|Michelangelo B|MB|
Gallieni|Maurizio|M|
Genovese|Umberto R|UR|

pulmonary thromboembolism
medical malpractice
forensic medicine
Medical law
forensic science
law


Effects of oral anticoagulant therapy in older medical in-patients with atrial fibrillation: a prospective cohort observational study.

Abstract:
BACKGROUND
Uncertainties about efficacy and safety of oral anticoagulant therapy (OAT) among older and frail medical patients with atrial fibrillation (AF) largely contribute to under-prescription of these drugs.

AIMS
In this prospective observational cohort study, we investigated mortality, and ischemic and hemorrhagic events, in hospital-discharged older patients with AF.

METHODS
Stroke and bleeding risk were evaluated using CHA2DS2-VASC and HAS-BLED scores. Comorbidity, frailty, cognitive and nutritional status and functional autonomy were evaluated using standardized scales. Independent associations between clinical variables, including OAT use, and all-cause mortality, fatal and non-fatal ischemic and hemorrhagic events, were evaluated. Further clinical outcomes comparison between patients treated with OAT and those untreated was performed after adjustment for significant differences in patient baseline characteristics with propensity score matching.

RESULTS
Of 452 patients included (mean age 81.6 years, 54.9 % women, roughly 30 % cognitively impaired and/or functionally dependent, mean CHA2DS2-VASC and HAS-BLED scores 4.6 and 2.8, respectively), 151 (33.4 %) died during a mean follow-up period of 300.5 days; ischemic and hemorrhagic stroke occurred in 4.0 and 0.4 % of patients, respectively, and major bleedings in 6.2 %.

DISCUSSION
After multivariate analysis, OAT at discharge was associated with lower overall mortality and reduced occurrence of ischemic stroke, the first finding being confirmed in propensity score matched analysis.

CONCLUSIONS
Among older vulnerable AF patients with high post discharge death rate, OAT was associated, among other multiple factors, with reduced mortality and lower occurrence of ischemic stroke.

Bo|Mario|M|
Li Puma|Federica|F|
Badinella Martini|Marco|M|
Falcone|Yolanda|Y|
Iacovino|Marina|M|
Grisoglio|Enrica|E|
Menditto|Elena|E|
Fonte|Gianfranco|G|
Brunetti|Enrico|E|
Isaia|Giovanni Carlo|GC|
D'Ascenzo|Fabrizio|F|
Gaita|Fiorenzo|F|

Anticoagulant therapy
Atrial fibrillation
Propensity score matching
Elderly


On the development and mechanics of delayed matching-to-sample performance.

Abstract: Despite its frequent use to assess effects of environmental and pharmacological variables on short-term memory, little is known about the development of delayed matching-to-sample (DMTS) performance. This study was designed to examine the dimensions and dynamics of DMTS performance development over a long period of exposure to provide a more secure foundation for assessing stability in future research. Six pigeons were exposed to a DMTS task with variable delays for 300 sessions (i.e., 18,000 total trials; 3,600 trials per retention interval). Percent-correct and log-d measures used to quantify the development of conditional stimulus control under the procedure generally and at each of five retention intervals (0, 2, 4, 8 and 16-s) individually revealed that high levels of accuracy developed relatively quickly under the shorter retention intervals, but increases in accuracy under the longer retention intervals sometimes were not observed until 100-150 sessions had passed, with some still increasing at Session 300. Analyses of errors suggested that retention intervals induced biases by shifting control from the sample stimulus to control by position, something that was predicted by observed response biases during initial training. These results suggest that although it may require a great deal of exposure to DMTS prior to obtaining asymptotic steady state, quantification of model parameters may help predict trends when extended exposure is not feasible.

Kangas|Brian D|BD|
Berry|Meredith S|MS|
Branch|Marc N|MN|

D000818:Animals
D001245:Association Learning
D003118:Color Perception
D010856:Columbidae
D003216:Conditioning, Operant
D004193:Discrimination Learning
D008570:Memory, Short-Term
D009949:Orientation
D011930:Reaction Time
D012055:Reinforcement Schedule
D012153:Retention, Psychology

delayed matching-to-sample
memory
pigeons
steady state
extended exposure
conditional discrimination
key peck
response bias


Implementation of a novel rehabilitation model of care across Alberta, Canada: a focused ethnography.

Abstract:
BACKGROUND
In 2017, a provincial health-system released a Rehabilitation Model of Care (RMoC) to promote patient-centred care, provincial standardisation and data-driven innovation. Eighteen early-adopter community-rehabilitation teams implemented the RMoC using a 1.5-year-long Innovation Learning Collaborative (in-person learning sessions; balanced scorecards). More research is required on developing, implementing and evaluating models of care. We aimed to explore experiences of early-adopter providers and provincial consultants involved in the community-rehabilitation RMoC implementation in Alberta, Canada.

METHODS
Using focused ethnography, we used focus groups (or interviews for feasibility/confidentiality) and aggregate, site-level data analysis of RMoC standardised metrics. Purposive sampling ensured representation across geography, service types and patient populations. Team-specific focus groups were onsite and led by a researcher-moderator and cofacilitator. A semistructured question guide promoted discussions on interesting/challenging occurrences; perceptions of RMoC impact and perceptions of successful implementation. Focus groups and interviews were audio-recorded and transcribed alongside field notes. Data collection and analysis were concurrent to saturation. Transcripts coding involves collapsing similar ideas into themes, with intertheme relationships identified. Rigour tactics included negative case analysis, thick description and audit trail.

RESULTS
We completed 11 focus groups and seven interviews (03/2018 to 01/2019) (n=45). Participants were 89.6% women, mostly Canadian trained and represented diverse rehabilitation professions. The implementation experience involved navigating emotions, operating among dynamics and integrating the RMoC details. Confident, satisfied early-adopter teams demonstrated traits including strong coping strategies; management support and being opportunistic and candid about failure. Teams faced common challenges (eg, emotions of change; delayed data access and lack of efficient, memorable communication across team and site). Implementation success targeted patient, team and system levels.

CONCLUSIONS
We recommend training priorities for future teams including evaluation training for novice teams; timelines for stepwise implementation; on-site, in-person time with a facilitator and full-team present and prolonged facilitated introductions between similar teams for long-term mentorship.

rehabilitation
health policy
health professions education
implementation science


Rationale and design of the PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage (PICASSO) study: A randomized controlled trial.

Abstract:
RATIONALE
Prior intracerebral haemorrhage and cerebral microbleeds may increase the risk of haemorrhagic stroke. However, the optimal long-term antiplatelet therapy and lipid management in these patients remain unclear.

AIM
PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage was designed to compare cilostazol and aspirin and to assess the effect of adding probucol, a lipid-lowering and anti-oxidative agent, in patients at high risk of haemorrhagic stroke.

SAMPLE SIZE ESTIMATE
The projected sample size is 1600 patients with at least 12 months of follow-up.

METHODS AND DESIGN
PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage is a randomized trial involving 67 institutes from 3 countries. Patients with non-cardioembolic ischemic stroke or transient ischemic attack within 180 days and with prior intracerebral haemorrhage or multiple cerebral microbleeds on gradient echo imaging are eligible. Enrolled patients are simultaneously randomized in a 2 × 2 factorial design: double-blind for cilostazol 200 mg/day vs. aspirin 100 mg/day, and an open-label, blind end-point evaluation for probucol 500 mg/day vs. non-probucol.

STUDY OUTCOMES
The co-primary end-points are the safety end-point of haemorrhagic stroke and the efficacy end-point of a composite of stroke, myocardial infarction, or vascular death. Time-to-event will be analyzed separately for each intervention: superiority testing for the safety of cilostazol over aspirin as well as the efficacy of probucol over non-probucol, and non-inferiority testing for the efficacy of cilostazol to aspirin.

DISCUSSION
PreventIon of CArdiovascular events in iSchemic Stroke patients with high risk of cerebral hemOrrhage is the largest secondary stroke prevention trial for informing antiplatelet therapy and lipid management in patients at high risk of haemorrhagic stroke.

Hong|Keun-Sik|KS|
Kim|Bum Joon|BJ|
Lee|Jun-Young|JY|
Kwon|Sun U|SU|
|||

intracerebral haemorrhage
microbleeds
cilostazol
probucol
cerebral infarction
clinical trial


The mechanisms generating community phylogenetic patterns change with spatial scale.

Abstract: Studies that test community assembly hypotheses in observational communities frequently evaluate patterns for plots or entire communities, yet studies that examine assembly patterns across spatial scales show that they are greatly influenced by scale. Here, we test the spatial dependency of patterns of relatedness and plant height for all individual herbaceous plants along five 40-m old-field transects (Southern Ontario, Canada). We identified each individual plant and measured its distance along the transect and its height, and we constructed a molecular phylogeny for all observed species. To uncover the scale at which community phylogenetic and trait similarities shift, we used partial Mantel correlograms and distance-based Moran Eigenvector Maps (dbMEMs). We found that communities shift from significantly overdispersed at relatively smaller scales (i.e., < 15 m) to spatially clustered at larger scales, showing that assembly mechanism influence depends on scale of observation. This pattern was observed for both phylogeny and height, but was the strongest when considering phylogeny only. These results reveal the importance of spatial scale when examining community phylogenetic or trait patterns, where finding support for one assembly mechanism at a single scale does not necessarily mean that other mechanisms are also not important for structuring community composition and diversity.

Spatial scale
Community assembly
Phylogeny
Coexistence
Habitat filtering


IL-4 and IL-15 promotion of virtual memory CD8+ T cells is determined by genetic background.

Abstract: Virtual memory (VM) CD8+ T cells are present in unimmunized mice, yet possess T-cell receptors specific for foreign antigens. To date, VM cells have only been characterized in C57BL/6 mice. Here, we assessed the cytokine requirements for VM cells in C57BL/6 and BALB/c mice. As reported previously, VM cells in C57BL/6 mice rely mostly on IL-15 and marginally on IL-4. In stark contrast, VM cells in BALB/c mice rely substantially on IL-4 and marginally on IL-15. Further, NKT cells are the likely source of IL-4, because CD1d-deficient mice on a BALB/c background have significantly fewer VM cells. Notably, this NKT/IL-4 axis contributes to appropriate effector and memory T-cell responses to infection in BALB/c mice, but not in C57BL/6 mice. However, the effects of IL-4 are manifest prior to, rather than during, infection. Thus, cytokine-mediated control of the precursor population affects the development of virus-specific CD8+ T-cell memory. Depending upon the genetic background, different cytokines encountered before infection may influence the subsequent ability to mount primary and memory anti-viral CD8+ T-cell responses.

Tripathi|Pulak|P|
Morris|Suzanne C|SC|
Perkins|Charles|C|
Sholl|Allyson|A|
Finkelman|Fred D|FD|
Hildeman|David A|DA|


Complex Class 1 Integron in a Clinical Escherichia coli Strain From Vietnam Carrying Both mcr-1 and bla NDM-1.

Abstract: The co-production of MCR and carbapenemase in Enterobacteriaceae has been previously reported. Here, we describe a clinical strain of Escherichia coli from Vietnam carrying both mcr-1 and bla NDM-1. Whole-genome sequencing showed that the genome of this strain consists of a 4,975,832-bp chromosome and four plasmids. The mcr-1 and bla NDM-1 genes are located on IncI2 and IncA/C2-type plasmids, respectively. Genetic analysis revealed the presence of a multidrug-resistant region with the structure of a novel complex class 1 integron including a class 1 integron region bearing two 5' conserved segments and one 3' conserved segment and two complete structures of ISCR1. The complex integron contains aminoglycoside resistance genes aadA2, aadB, strA, strB, and aphA6, quinolone resistance gene qnrA1, extended-spectrum β-lactamase gene bla OXA- 4, and a Tn125-like transposon bearing bla NDM-1. In addition, the dfrA12-gcuF-aadA2-cmlA1-aadA1-qacH gene cassette array belonging to the sul3-type integron was also identified, but the region found downstream of the gene cassette array is the IS440-tet(M)-IS26 element instead of the sul3 gene. The results further support that Enterobacteriaceae isolates co-harboring mcr and bla NDM are widely being distributed. The structural characteristics of the complex integron reveal that ISCR1 elements play an important role in the mobilization of bla NDM-1 and the development of multidrug-resistant regions.

Le-Vo|Hong-Ngoc|HN|
Tran|Phuong Thi-Bich|PT|
Le|Lien|L|
Matsumoto|Yuki|Y|
Motooka|Daisuke|D|
Nakamura|Shota|S|
Jones|James W|JW|
Iida|Tetsuya|T|
Cao|Van|V|

complex class 1 integron
Escherichia coli
mcr-1
carbapenemase
sul3-type integron
blaNDM–1
colistin


Mutation of the co-chaperone Tsc1 in bladder cancer diminishes Hsp90 acetylation and reduces drug sensitivity and selectivity.

Abstract: The molecular chaperone Heat shock protein 90 (Hsp90) is essential for the folding, stability, and activity of several drivers of oncogenesis. Hsp90 inhibitors are currently under clinical evaluation for cancer treatment, however their efficacy is limited by lack of biomarkers to optimize patient selection. We have recently identified the tumor suppressor tuberous sclerosis complex 1 (Tsc1) as a new co-chaperone of Hsp90 that affects Hsp90 binding to its inhibitors. Highly variable mutations of TSC1 have been previously identified in bladder cancer and correlate with sensitivity to the Hsp90 inhibitors. Here we showed loss of TSC1 leads to hypoacetylation of Hsp90-K407/K419 and subsequent decreased binding to the Hsp90 inhibitor ganetespib. Pharmacologic inhibition of histone deacetylases (HDACs) restores acetylation of Hsp90 and sensitizes Tsc1-mutant bladder cancer cells to ganetespib, resulting in apoptosis. Our findings suggest that TSC1 status may predict response to Hsp90 inhibitors in patients with bladder cancer, and co-targeting HDACs can sensitize tumors with Tsc1 mutations to Hsp90 inhibitors.

Woodford|Mark R|MR|
Hughes|Michael|M|
Sager|Rebecca A|RA|
Backe|Sarah J|SJ|
Baker-Williams|Alexander J|AJ|
Bratslavsky|Michael S|MS|
Jacob|Joseph M|JM|
Shapiro|Oleg|O|
Wong|Michael|M|
Bratslavsky|Gennady|G|
Bourboulia|Dimitra|D|
Mollapour|Mehdi|M|

bladder cancer
Tsc1 (Hamartin)
Tsc2 (Tuberin)
heat shock protein (Hsp90)
tuberous sclerosis complex (TSC)


Impacts of landscape patterns on water-related ecosystem services under natural restoration in Liaohe River Reserve, China.

Abstract: Understanding changes in ecosystem services and their drivers is important for effective riparian ecosystem conservation and restoration. In the study, changes in water-related ecosystem services (soil conservation, water purification, and water yield) from 2007 to 2015 in Liaohe River Reserve, China were analyzed using the Integrated Valuation of Ecosystem Services and Trade-offs model. Impacts of landscape patterns on ecosystem services for different stages of restoration, i.e., farmland abandonment and natural succession stages were determined by stepwise regression analysis, respectively. The results showed that landscape fragmentation, landscape diversity, farmland fragmentation and grassland aggregation increased at the farmland abandonment stage. Landscape aggregation and diversity increased, whereas farmland fragmentation and grassland fragmentation decreased at the natural succession stage. Water-related ecosystem services improved since farmland abandonment, but water yield decreased from 1.57 × 106 m3 to 1.47 × 106 m3 at natural succession stage from 2011 to 2015. Water yield dynamics both at farmland abandonment and natural restoration stages were not significantly associated with landscape metrics. Dynamics of soil retention and water purification services at the farmland abandonment stage were significantly affected by landscape patch numbers, farmland division, and grassland aggregation. Interspersion and juxtaposition between different patch types, farmland edge density, grassland division, and grassland aggregation played significant roles in the dynamics of soil retention and water purification services at the natural restoration stage. The results provide scientific guidance for riparian management at the landscape scale to better restore water-related ecosystem services.

Xia|Huijuan|H|
Kong|Weijing|W|
Zhou|Gang|G|
Sun|Osbert Jianxin|OJ|

Ecosystem services
Farmland abandonment
Landscape metrics
Riparian restoration
Vegetation succession


The long term predictive value of preoperative pressure flow studies in the resolution of overactive bladder after insertion of a retropubic midurethral sling.

Abstract:
AIMS
To identify if the short term association of pressure flow rates with resolution of overactive bladder (OAB) is maintained in the long term in patients with mixed urodynamic incontinence treated with a retropubic midurethral sling. To assess if other demographic factors are associated with the long term resolution of OAB.

METHODS
This was follow up study of a consecutive case series of 100 patients treated with a MUS at a single center followed up with questionnaires. Preoperative pressure flow studies were compared to the resolution of urgency and urgency incontinence after surgery.

RESULTS
A total of 6.25 years after surgery, resolution of urgency and urgency incontinence was associated with a higher preoperative flow rate (26.7 mL/s vs 19.1 mL/s P = 0.02) and a higher flow rate centile (33.1 vs 14.0 P = 0.01). No other demographic parameters were associated with resolution of OAB.

CONCLUSIONS
The long term outcome and resolution of urgency and urgency incontinence can be predicted by preoperative pressure flow studies over 6 years after surgery.

OAB
mixed urodynamic incontinence
TVT
detrusor overactivity
persistence


Captive chimpanzees' manual laterality in tool use context: Influence of communication and of sociodemographic factors.

Abstract: Understanding variations of apes' laterality between activities is a central issue when investigating the evolutionary origins of human hemispheric specialization of manual functions and language. We assessed laterality of 39 chimpanzees in a non-communication action similar to termite fishing that we compared with data on five frequent conspecific-directed gestures involving a tool previously exploited in the same subjects. We evaluated, first, population-level manual laterality for tool-use in non-communication actions; second, the influence of sociodemographic factors (age, sex, group, and hierarchy) on manual laterality in both non-communication actions and gestures. No significant right-hand bias at the population level was found for non-communication tool use, contrary to our previous findings for gestures involving a tool. A multifactorial analysis revealed that hierarchy and age particularly modulated manual laterality. Dominants and immatures were more right-handed when using a tool in gestures than in non-communication actions. On the contrary, subordinates, adolescents, young and mature adults as well as males were more right-handed when using a tool in non-communication actions than in gestures. Our findings support the hypothesis that some primate species may have a specific left-hemisphere processing gestures distinct from the cerebral system processing non-communication manual actions and to partly support the tool use hypothesis.

Prieur|Jacques|J| Pika|Simone|S| Blois-Heulin|Catherine|C| Barbu|Stéphanie|S|

Gestures
Hemispheric lateralization
Intraspecific communication
Object manipulations
Pan troglodytes


CCL23: a new CC chemokine involved in human brain damage.

Abstract:
BACKGROUND
CCL23 role in the inflammatory response after acute brain injuries remains elusive. Here, we evaluated whether CCL23 blood levels associate with acquired cerebral lesions and determined CCL23 predictive capacity for assessing stroke prognosis. We used preclinical models to study the CCL23 homologous chemokines in rodents, CCL9 and CCL6.

METHODS
Baseline CCL23 blood levels were determined on 245 individuals, including ischaemic strokes (IS), stroke mimics and controls. Temporal profile of circulating CCL23 was explored from baseline to 24 h in 20 of the IS. In an independent cohort of 120 IS with a 3-month follow-up, CCL23 blood levels were included in logistic regression models to predict IS outcome. CCL9/CCL6 cerebral expression was evaluated in rodent models of brain damage. Both chemokines were also profiled in circulation and histologically located on brain following ischaemia.

RESULTS
Baseline CCL23 blood levels did not discriminate IS, but permitted an accurate discrimination of patients presenting acute brain lesions (P = 0.003). IS exhibited a continuous increase from baseline to 24 h in circulating CCL23 (P < 0.001). Baseline CCL23 blood levels resulted an independent predictor of IS outcome at hospital discharge (ORadj : 19.702 [1.815-213.918], P = 0.014) and mortality after 3 months (ORadj : 21.47 [3.434-134.221], P = 0.001). In preclinics, expression of rodent chemokines in neurons following cerebral lesions was elevated. CCL9 circulating levels decreased early after ischaemia (P < 0.001), whereas CCL6 did not alter within the first 24 h after ischaemia.

CONCLUSIONS
Although preclinical models do not seem suitable to characterize CCL23, it might be a novel promising biomarker for the early diagnosis of cerebral lesions and might facilitate the prediction of stroke patient outcome.

Simats|A|A| García-Berrocoso|T|T| Penalba|A|A| Giralt|D|D| Llovera|G|G| Jiang|Y|Y| Ramiro|L|L| Bustamante|A|A| Martinez-Saez|E|E| Canals|F|F| Wang|X|X| Liesz|A|A| Rosell|A|A| Montaner|J|J|0000-0003-4845-2279

CCL23
brain injury
stroke
biomarker
inflammation


Commentary on Blood group AB is associated with poor outcomes in infants with necrotizing enterocolitis.

Abstract: This is a commentary on the manuscript titled "Blood Group AB is Associated with Poor Outcomes in Infants with Necrotizing Enterocolitis" by Dos Santos Martins R, Kool E, Kalteren W, et al.

D001789:Blood Group Antigens
D020345:Enterocolitis, Necrotizing
D006801:Humans
D007223:Infant
D007231:Infant, Newborn
D007232:Infant, Newborn, Diseases

Necrotizing enterocolitis
ABO blood group
Blood group antagonism
Fetal-maternal incompatibility
Prematurity
Red blood cells transfusions


Transforming Growth Factor-β and Oxidative Stress in Cancer: A Crosstalk in Driving Tumor Transformation.

Abstract: Cancer metabolism involves different changes at a cellular level, and altered metabolic pathways have been demonstrated to be heavily involved in tumorigenesis and invasiveness. A crucial role for oxidative stress in cancer initiation and progression has been demonstrated; redox imbalance, due to aberrant reactive oxygen species (ROS) production or deregulated efficacy of antioxidant systems (superoxide dismutase, catalase, GSH), contributes to tumor initiation and progression of several types of cancer. ROS may modulate cancer cell metabolism by acting as secondary messengers in the signaling pathways (NF-kB, HIF-1α) involved in cellular proliferation and metastasis. It is known that ROS mediate many of the effects of transforming growth factor β (TGF-β), a key cytokine central in tumorigenesis and cancer progression, which in turn can modulate ROS production and the related antioxidant system activity. Thus, ROS synergize with TGF-β in cancer cell metabolism by increasing the redox imbalance in cancer cells and by inducing the epithelial mesenchymal transition (EMT), a crucial event associated with tumor invasiveness and metastases. Taken as a whole, this review is addressed to better understanding this crosstalk between TGF-β and oxidative stress in cancer cell metabolism, in the attempt to improve the pharmacological and therapeutic approach against cancer.


Nest use and patterns of egg laying and damage by 4 strains of laying hens in an aviary system.

Abstract: Laying hens are strongly motivated to use nests for egg laying, and alternative production systems (e.g., aviaries) provide artificial sites to meet this need and ensure efficient collection of clean, undamaged eggs. However, nests are typically not provided to allow simultaneous use by all hens; therefore, competition or mislaid eggs can result. To understand the influence of strain on laying eggs outside nests and damage to eggs, we compared daily patterns of nests use and egg laying among 4 laying hen strains (Hy-Line Brown (HB), Bovans Brown (BB), DeKalb White (DW), and Hy-Line W36 (W36)). Hens were observed over 3 consecutive days in aviaries with colony nests in the enclosure's top tier (2 nests/unit, 4 aviary units/strain, 144 hens/unit). The number and location of hens in nests and the number, location and condition of eggs throughout aviaries were recorded. Most eggs (90 to 95%) were laid in nests; however, brown hens consistently laid more non-nest eggs and damaged more eggs than white hens (P ≤ 0.05). Higher nest occupancy by brown hens was correlated with more non-nest and damaged eggs (P ≤ 0.05). In the morning, brown hens occupied more nest space and laid more nest eggs than white hens (e.g., HB vs. DW: 82.97 and 34.66% of space; 91.35 and 68.73% of nest eggs; P ≤ 0.05). At midday, white hens occupied more nest space and laid more nest eggs than brown hens (e.g., HB vs. DW: 28.47 and 15.81% of space; 27.39 and 8.29% of nest eggs; P ≤ 0.05). Brown hens preferred right nest compartments and laid more eggs there, whereas white hens preferred left compartments and W36 laid more eggs there (P ≤ 0.05). These findings indicate that different strains of hens have different patterns of nest use and laying behavior. In brown hens, heavy morning nest use was related to laying eggs outside nests and more damaged eggs, suggesting insufficient space for oviposition in nests. Specific facility design should be matched to hens' preferences to accommodate behavioral needs of different strains.

Villanueva|S|S|
Ali|A B A|ABA|
Campbell|D L M|DLM|
Siegford|J M|JM|

nest
egg laying
strain
laying hen
aviary


An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia--full report.

Abstract: An international panel of the International Atherosclerosis Society has developed a new set of recommendations for the management of dyslipidemia. The panel identifies non--high-density lipoprotein cholesterol as the major atherogenic lipoprotein. Primary and secondary prevention are considered separately. Optimal levels for atherogenic lipoproteins are derived for the two forms of prevention. For primary prevention, the recommendations emphasize lifestyle therapies to reduce atherogenic lipoproteins; drug therapy is reserved for subjects at greater risk. Risk assessment is based on estimation of lifetime risk according to differences in baseline population risk in different nations or regions. Secondary prevention emphasizes use of cholesterol-lowering drugs to attain optimal levels of atherogenic lipoproteins.

Dyslipidemia
Cholesterol
Lifestyle therapies
Lifetime risk
Metabolic syndrome
Statins


Grain and dietary fiber intake and bladder cancer risk: a pooled analysis of prospective cohort studies.

Abstract:
BACKGROUND
Higher intakes of whole grains and dietary fiber have been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for cancer.

OBJECTIVES
Because the evidence of association with bladder cancer (BC) is limited, we aimed to assess associations with BC risk for intakes of whole grains, refined grains, and dietary fiber.

METHODS
We pooled individual data from 574,726 participants in 13 cohort studies, 3214 of whom developed incident BC. HRs, with corresponding 95% CIs, were estimated using Cox regression models stratified on cohort. Dose-response relations were examined using fractional polynomial regression models.

RESULTS
We found that higher intake of total whole grain was associated with lower risk of BC (comparing highest with lowest intake tertile: HR: 0.87; 95% CI: 0.77, 0.98; HR per 1-SD increment: 0.95; 95% CI: 0.91, 0.99; P for trend: 0.023). No association was observed for intake of total refined grain. Intake of total dietary fiber was also inversely associated with BC risk (comparing highest with lowest intake tertile: HR: 0.86; 95% CI: 0.76, 0.98; HR per 1-SD increment: 0.91; 95% CI: 0.82, 0.98; P for trend: 0.021). In addition, dose-response analyses gave estimated HRs of 0.97 (95% CI: 0.95, 0.99) for intake of total whole grain and 0.96 (95% CI: 0.94, 0.98) for intake of total dietary fiber per 5-g daily increment. When considered jointly, highest intake of whole grains with the highest intake of dietary fiber showed 28% reduced risk (95% CI: 0.54, 0.93; P for trend: 0.031) of BC compared with the lowest intakes, suggesting potential synergism.

CONCLUSIONS
Higher intakes of total whole grain and total dietary fiber are associated with reduced risk of BC individually and jointly. Further studies are needed to clarify the underlying mechanisms for these findings.

Yu|Evan Y W|EYW|
Wesselius|Anke|A|
Mehrkanoon|Siamak|S|
Brinkman|Maree|M|
van den Brandt|Piet|P|
White|Emily|E|
Weiderpass|Elisabete|E|
Le Calvez-Kelm|Florence|F|
Gunter|Marc|M|
Huybrechts|Inge|I|
Liedberg|Fredrik|F|
Skeie|Guri|G|
Tjonneland|Anne|A|
Riboli|Elio|E|
Giles|Graham G|GG|
Milne|Roger L|RL|
Zeegers|Maurice P|MP|

grain
dietary fiber
bladder cancer
cohort study
dose-response analysis


The dilemma of reporting suspicions of child maltreatment in pediatric dentistry.

Abstract: This study examined the factors that lead specialists in pediatric dentistry to suspect child abuse or neglect and the considerations that influence the decision to report these suspicions to social services. Focus group discussions were used to identify new aspects of child maltreatment suspicion and reporting. Such discussions illuminate the diversity of informants' experiences, opinions, and reflections. Focus groups included 19 specialists and postgraduate students in pediatric dentistry. We conducted video-recorded focus group discussions at the informants' dental clinics. All sessions lasted approximately 1.5 h. We transcribed the discussions verbatim and studied the transcripts using thematic analysis, a method well-suited to evaluating the experiences discussed and how the informants understand them. The analysis process elicited key concepts and identified one main theme, which we labeled 'the dilemma of reporting child maltreatment'. We found this dilemma to pervade a variety of situations and divided it into three sub-themes: to support or report; differentiating concern for well-being from maltreatment; and the supportive or unhelpful consultation. Reporting a suspicion about child maltreatment seems to be a clinical and ethical dilemma arising from concerns of having contradicting professional roles, difficulties confirming suspicions of maltreatment, and perceived shortcomings in the child-protection system.

Kvist|Therese|T| Wickström|Anette|A| Miglis|Isabelle|I| Dahllöf|Göran|G|

D002648:Child
D002649:Child Abuse
D002651:Child Advocacy
D002669:Child Welfare
D003657:Decision Making
D019140:Dental Care for Children
D003812:Dentist-Patient Relations
D003815:Dentists
D004990:Ethics, Dental
D017144:Focus Groups
D006801:Humans
D019221:Mandatory Reporting
D010290:Parents
D010377:Pediatric Dentistry
D024382:Professional Role
D011368:Professional-Family Relations
D012017:Referral and Consultation
D012947:Social Work
D014741:Video Recording

child abuse
dentist-patient relations
mandatory reporting
professional practice


Selective blockage of Serratia marcescens ShlA by nickel inhibits the pore-forming toxin-mediated phenotypes in eukaryotic cells.

Abstract: Serratia marcescens is an opportunistic pathogen with increasing incidence in clinical settings. This is mainly attributed to the timely expression of a wide diversity of virulence factors and intrinsic and acquired resistance to antibiotics, including β-lactams, aminoglycosides, quinolones, and polypeptides. For these reasons, S. marcescens has been recently categorised by the World Health Organization as one priority to strengthen efforts directed to develop new antibacterial agents. Therefore, it becomes critical to understand the underlying mechanisms that allow Serratia to succeed within the host. S. marcescens ShlA pore-forming toxin mediates phenotypes that alter homeostatic and signal transduction pathways of host cells. It has been previously demonstrated that ShlA provokes cytotoxicity, haemolysis and autophagy and also directs Serratia egress and dissemination from invaded nonphagocytic cells. However, molecular details of ShlA mechanism of action are still not fully elucidated. In this work, we demonstrate that Ni2+ selectively and reversibly blocks ShlA action, turning wild-type S. marcescens into a shlA mutant strain phenocopy. Combined use of Ni2+ and calcium chelators allow to discern ShlA-triggered phenotypes that require intracellular calcium mobilisation and reveal ShlA function as a calcium channel, providing new insights into ShlA mode of action on target cells.

Serratia
ShlA
nickel
pore-forming toxin
calcium channel


Renal threshold for glucose reabsorption predicts diabetes improvement by sodium-glucose cotransporter 2 inhibitor therapy.

Abstract: In the present study we examined the efficacy of sodium-glucose cotransporter 2 inhibitors on improvement of glycated hemoglobin (HbA1c) in comparison with the renal threshold for glucose reabsorption in patients with type 2 diabetes mellitus. Patients visited the hospital once a month for a regular follow-up examination with the determination of blood glucose and HbA1c levels, and urinary glucose concentration from spot urine samples. Patient samples were compared before and after ipragliflozin administration. We defined the renal threshold for glucose reabsorption as the lowest blood glucose level that correlated with the first detectable appearance of urine glucose. These data showed a significant negative correlation between improvement of HbA1c level and renal threshold for glucose reabsorption in patients treated with the sodium-glucose cotransporter 2 inhibitor. These findings show that patients who have a higher renal threshold for glucose reabsorption can be expected to more effectively respond to sodium-glucose cotransporter 2 inhibitor therapy in terms of lowering HbA1c levels.

Osaki|Aya|A| Okada|Shuichi|S| Saito|Tsugumichi|T| Yamada|Eijiro|E| Ono|Kumeo|K| Niijima|Yawara|Y| Hoshi|Hiroto|H| Yamada|Masanobu|M|

D000077203:Sodium-Glucose Transporter 2 Inhibitors

Sodium-glucose cotransporter 2 inhibitor


Implementation of personalized medicine in Central-Eastern Europe: pitfalls and potentials based on citizen's attitude.

Abstract:
Objective
Next-generation sequencing is increasingly utilized worldwide as a research and diagnostic tool and is anticipated to be implemented into everyday clinical practice. Since Central-Eastern European attitude toward genetic testing, especially broad genetic testing, is not well known, we performed a survey on this issue among Hungarian participants.

Methods
A self-administered questionnaire was distributed among patients and patient relatives at our neurogenetic outpatient clinic. Members of the general population were also recruited via public media. We used chi-square testing and binary logistic regression to examine factors influencing attitude.

Results
We identified a mixed attitude toward genetic testing. Access to physician consultation positively influenced attitude. A higher self-determined genetic familiarity score associated with higher perceived genetic influence score, which in turn associated with greater willingness to participate in genetic testing. Medical professionals constituted a skeptical group.

Conclusions
We think that given the controversies and complexities of the next-generation sequencing field, the optimal clinical translation of NGS data should be performed in institutions which have the unique capability to provide interprofessional health education, transformative biomedical research, and crucial patient care. With optimization of the clinical translational process, improvement of genetic literacy may increase patient engagement and empowerment.

Relevance of the article for predictive preventive and personalized medicine
The paper highlights that in countries with relatively low-genetic literacy, a special strategy is needed to enhance the implementation of personalized medicine.

Balicza|Peter|P|
Terebessy|Andras|A|
Grosz|Zoltan|Z|
Varga|Noemi Agnes|NA|
Gal|Aniko|A|
Fekete|Balint Andras|BA|
Molnar|Maria Judit|MJ|

Predictive preventive personalized medicine


Applying synchronous fluorescence and UV-vis spectra combined with two-dimensional correlation to characterize structural composition of DOM from urban black and stinky rivers.

Abstract: UV-visible spectroscopy and synchronous fluorescence spectroscopy (SFS) combined with two-dimensional correlation spectroscopy (2D-COS) were applied for extracting fluorescence components, tracing organic functional groups, and revealing variations of dissolved organic matter (DOM) in Puhe River. Water samples were collected from the mainstream and two tributaries (Nanxiaohe River and Huangnihe River). DOM in three rivers was composed of protein-like fluorescent (PLF), microbial humus-like fluorescent (MHLF), fulvic-like fluorescent (FLF), and humic-like fluorescent components, which were relative to aromatic groups, phenolic groups, carboxylic groups, and microbial products. The PLF and MHLF were dominated in DOM fractions in the rivers, and the average content of the PLF was the highest in Nanxiaohe River. Humification degree of DOM was the highest in Puhe River, followed by Huangnihe River and Nanxiaohe River. However, molecular mass of DOM in Puhe River was the lowest, followed by Huangnihe River and Nanxiaohe River. Based on the 2D-COS of the SFS and UV-visible spectra, the variation order of DOM fractions in Puhe River was PLF → MHLF → FLF, and the PLF was consistent with the phenolic groups, aromatic groups, and carboxylic groups, but the adverse trend with the microbial products. The variation order in Nanxiaohe River was MHLF → PLF → FLF, and the MHLF was consistent with the aromatic groups, phenolic groups, carboxylic groups, and microbial products. The variation order in Huangnihe River was MHLF → PLF → FLF too, and the PLF was consistent with the carboxylic groups and aromatic groups. The results of the present study demonstrate that UV-visible spectroscopy and SFS combined with 2D-COS are useful methods to characterize structural composition of DOM from urban black and stinky rivers so as to investigate their pollution status.

Liu|Dongping|D| Yu|Huibin|H| Gao|Hongjie|H| Feng|Huijuan|H| Zhang|Guangcai|G|


Detection methods for influenza A H1N1 virus with special reference to biosensors: a review.

Abstract: H1N1 (Swine flu) is caused by influenza A virus, which is a member of Orthomyxoviridae family. Transmission of H1N1 occurs from human to human through air or sometimes from pigs to humans. The influenza virus has different RNA segments, which can reassert to make new virus strain with the possibility to create an outbreak in unimmunized people. Gene reassortment is a process through which new strains are emerging in pigs, as it has specific receptors for both human influenza and avian influenza viruses. H1N1 binds specifically with an α-2,6 glycosidic bond, which is present in human respiratory tract cells as well as in pigs. Considering the fact of fast multiplication of viruses inside the living cells, rapid detection methods need an hour. Currently, WHO recommended methods for the detection of swine flu include real-time PCR in specific testing centres that take 3-4 h. More recently, a number of methods such as Antigen-Antibody or RT-LAMP and DNA biosensors have also been developed that are rapid and more sensitive. This review describes the various challenges in the diagnosis of H1N1, and merits and demerits of conventional vis-à-vis latest methods with special emphasis on biosensors.

R|Ravina|R|
Dalal|Anita|A|
Mohan|Hari|H|
Prasad|Minakshi|M|
Pundir|C S|CS|

D015374:Biosensing Techniques
D004261:DNA Replication
D004279:DNA, Viral
D006801:Humans
D053118:Influenza A Virus, H1N1 Subtype
D007251:Influenza, Human
D011237:Predictive Value of Tests
D015203:Reproducibility of Results
D019562:Viral Load
D014773:Virology
D014779:Virus Replication
D057188:Workflow

Swine flu
Orthomyxoviridae
RT-LAMP
DNA biosensors
A (H1N1)
Real Time-PCR


Differentially localized survivin and STAT3 as markers of gastric cancer progression: Association with Helicobacter pylori.

Abstract:
BACKGROUND
Localization and differential expression of STAT3 and survivin in cancer cells are often related to distinct cellular functions. The involvement of survivin and STAT3 in gastric cancer has been reported in separate studies but without clear understanding of their kinetics in cancer progression.

METHODS
We examined intracellular distribution of STAT3 and survivin in gastric adenocarcinoma and compared it with normal and precancer tissues using immunoblotting and immunohistochemistry.

RESULTS
Analysis of a total of 156 gastric samples comprising 61 histologically normal, 30 precancerous tissues (comprising intestinal metaplasia and dysplasia), and 65 adenocarcinomas, collected as endoscopic biopsies from treatment naïve study participants, revealed a significant (P < .001) increase in overall protein levels. Survivin expression was detectable in both cytoplasmic (90.8%) and nuclear (87.7%) compartments in gastric adenocarcinomas lesions. Precancerous dysplastic gastric lesions exhibited a moderate survivin expression (56.7%) localized in cytoplasmic compartment. Similarly, STAT3 and pSTAT3 expression was detected at high level in gastric cancer lesions. The levels of compartmentalized expression of survivin and STAT3/pSTAT3 correlated in precancerous and adenocarcinoma lesions. Although overexpression of these proteins was found associated with the tobacco use and alcohol consumption, their expression invariably and strongly correlated with concurrent Helicobacter pylori infection. Receiver operating characteristic analysis of nuclear survivin, STAT3, and pSTAT3 in different study groups showed acceptable positive and negative predictive values with area under the curve above 0.8 (P < .001).

CONCLUSION
Overall, our results suggest that overall increase in survivin and STAT3 and their subcellular localization are key determinants of gastric cancer progression, which can be collectively used as potential disease biomarkers and therapeutic targets for gastric cancer.

Pandey|Arvind|A|0000-0002-9942-5468
Tripathi|Satyendra Chandra|SC|
Shukla|Shirish|S|
Mahata|Sutapa|S|
Vishnoi|Kanchan|K|
Misra|Sri Prakash|SP|
Misra|Vatsala|V|
Mitra|Sankar|S|
Dwivedi|Manisha|M|
Bharti|Alok C|AC|0000-0002-5996-2832

survivin
STAT3
gastric adenocarcinoma
dysplasia
intestinal metaplasia IV


Fast 3D magnetic resonance fingerprinting for a whole-brain coverage.

Abstract:
PURPOSE
The purpose of this study was to accelerate the acquisition and reconstruction time of 3D magnetic resonance fingerprinting scans.

METHODS
A 3D magnetic resonance fingerprinting scan was accelerated by using a single-shot spiral trajectory with an undersampling factor of 48 in the x-y plane, and an interleaved sampling pattern with an undersampling factor of 3 through plane. Further acceleration came from reducing the waiting time between neighboring partitions. The reconstruction time was accelerated by applying singular value decomposition compression in k-space. Finally, a 3D premeasured B1 map was used to correct for the B1 inhomogeneity.

RESULTS
The T1 and T2 values of the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI phantom showed a good agreement with the standard values, with an average concordance correlation coefficient of 0.99, and coefficient of variation of 7% in the repeatability scans. The results from in vivo scans also showed high image quality in both transverse and coronal views.

CONCLUSIONS
This study applied a fast acquisition scheme for a fully quantitative 3D magnetic resonance fingerprinting scan with a total acceleration factor of 144 as compared with the Nyquist rate, such that 3D T1 , T2 , and proton density maps can be acquired with whole-brain coverage at clinical resolution in less than 5 min. Magn Reson Med 79:2190-2197, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Ma|Dan|D| Jiang|Yun|Y| Chen|Yong|Y| McGivney|Debra|D| Mehta|Bhairav|B| Gulani|Vikas|V| Griswold|Mark|M|


Diagnosis of constipation does not correlate with trans-abdominal ultrasound of rectal distention.

Abstract:
INTRODUCTION
Constipation has been shown to have a significant impact on lower urinary tract symptoms (LUTS) in children, and treatment of constipation in children with bowel bladder dysfunction (BBD) has been shown to improve or completely resolve LUTS in many cases. Recent studies utilizing trans-abdominal ultrasound (US) to assess stool burden have correlated diagnosis of constipation with US appearance of rectal stool. An US scoring tool was published in 2008 to assess stool burden, showing linear correlation with constipation severity by symptom questionnaire in an outpatient pediatric constipation clinic population. We hypothesized that this US scoring tool would correlate with constipation symptoms in our outpatient pediatric urology population.

METHODS
In 2010, our pediatric urology outpatient clinic began administering a previously published validated BBD questionnaire to new toilet-trained patients, containing three questions addressing bowel function. Patients in our clinic undergoing trans-abdominal US of the bladder also have assessment of their stool burden by the previously published US scoring tool. We retrospectively reviewed patient charts beginning in June 2013 who had undergone trans-abdominal US of the bladder, gathering data on the first 100 patients with a complete BBD questionnaire and a completed stool burden US scoring tool.

RESULTS
Chart review of 272 consecutive patients was required to enroll 100 patients with a completed US scoring of stool burden and a completed BBD questionnaire. Of these 272 patients, 225 (82%) had a complete scoring of stool burden during their US examination. BBD questionnaires were complete in 107 of 272 patients (39%). Median patient age was 8.2 years, with 69% of patients being female. The most common diagnosis was incontinence or bladder dysfunction (41%). Only one patient (1%) had constipation as the primary diagnosis for their visit. Linear regression analysis showed no correlation of US score to patient reported frequency of bowel movement, frequency of hard stool, frequency of fecal incontinence, or all three symptoms combined. When investigating the subgroup of patients who had diagnoses of BBD/incontinence, this group was seen to have higher mean symptom scores than the entire cohort as a whole, but US scores were still widely variable and again did not correlate with symptom scores.

CONCLUSION
US examination has previously been shown to correlate with symptom severity for children with chronic constipation in a pediatric constipation clinic setting. However, in a pediatric urology outpatient clinic setting at our institution, US examination did not correlate with patient reported symptoms.

Mason|Matthew D|MD|
Ching|Christina B|CB|
Clayton|Douglass B|DB|
Thomas|John C|JC|
Pope|John C|JC|
Adams|Mark C|MC|
Brock|John W|JW|
Tanaka|Stacy T|ST|

Constipation
Ultrasound
Lower urinary tract symptoms
Bowel bladder dysfunction


A novel role for STOMATAL CARPENTER 1 in stomata patterning.

Abstract:
BACKGROUND
Guard cells (GCs) are specialised cells within the plant epidermis which form stomatal pores, through which gas exchange can occur. The GCs derive through a specialised lineage of cell divisions which is specified by the transcription factor SPEECHLESS (SPCH), the expression of which can be detected in undifferentiated epidermal cells prior to asymmetric division. Other transcription factors may act before GC specification and be required for correct GC patterning. Previously, the DOF transcription factor STOMATAL CARPENTER 1 (SCAP1) was shown to be involved in GC function, by activating a set of GC-specific genes required for GC maturation and activity. It is thus far unknown whether SCAP1 can also affect stomatal development.

RESULTS
Here we show that SCAP1 expression can also be observed in young leaf primordia, before any GC differentiation occurs. The study of transgenic plants carrying a proSCAP1:GUS-GFP transcriptional fusion, coupled with qPCR analyses, indicate that SCAP1 expression peaks in a temporal window which is coincident with expression of stomatal patterning genes. Independent scap1 loss-of-function mutants have a reduced number of GCs whilst SCAP1 over expression lines have an increased number of GCs, in addition to altered GC distribution and spacing patterns. The study of early markers for stomatal cell lineage in a background carrying gain-of-function alleles of SCAP1 revealed that, compared to the wild type, an increased number of protodermal cells are recruited in the GC lineage, which is reflected in an increased number of meristemoids.

CONCLUSIONS
Our results suggest an early role for SCAP1 in GC differentiation. We propose that a function of SCAP1 is to integrate different aspects of GC biology including specification, spacing, maturation and function.

Castorina|Giulia|G| Fox|Samantha|S| Tonelli|Chiara|C| Galbiati|Massimo|M| Conti|Lucio|L|0000-0002-7837-4227

D018506:Gene Expression Regulation, Plant

Arabidopsis
AtMYB60 (AT1G08810)
DOF-type transcription factors
Guard Cells development
SCAP1 (AT5G65590)
SPCH (AT5G53210)


Nigerian foods of probiotics relevance and chronic metal exposure: a systematic review.

Abstract: Probiotics are functional foods with a wide armamentarium of health benefits in man including metal chelation. Given the unacceptable blood lead levels and the near ignorance or negligence of heavy metals in both diagnoses and management of diseases in Nigeria, it is feared that these metals are involved in the aetiogenesis of several ailments from preeclampsia, metabolic syndrome, cancer, etc. This is an insight on Nigerian fermented foods and their possible role as metal chelators in the management of the chronic heavy metal exposure in Nigeria. One hundred and five articles fulfilled the inclusion criteria. Google scholar, PubMed and SCOPUS were searched for articles reporting fermented foods and probiotics in Nigeria. Only studies published in English Language were included, but there was no limitation in year of study. One hundred and five articles fulfilled the inclusion criteria. Studies from some African countries suggest that fermented foods of probiotics relevance have effectively shown metal chelation properties. Consumption of Nigerian fermented foods may hold a promise in checking the high body burden of heavy metals in Nigeria. Graphic abstract.

Orisakwe|Orish Ebere|OE|
Amadi|Cecilia Nwadiuto|CN|
Frazzoli|Chiara|C|
Dokubo|Awolayeofori|A|

Probiotics
Chelation
Heavy metals
Fermented foods
Bifidobacteria
Lactobacillus


How do I steer this thing? Using dendritic cell targeted vaccination to more effectively guide the antitumor immune response with combination immunotherapy.

Abstract: Mounting an immune response sufficient to eradicate a tumor is the goal of modern immunotherapy. Single agent therapies with checkpoint inhibitors or costimulatory molecule agonists are effective only for a small portion of all treated patients. Combined therapy, e.g., CTLA-4 and PD-1 checkpoint blockade, is a more effective treatment modality, but in preclinical studies OX40 agonism with CTLA-4 blockade using monoclonal antibodies (aOX40/aCTLA-4) failed to induce tumor regression of larger, more established tumors. We hypothesized that administration of a vaccine with a tumor-associated antigen targeted to the appropriate antigen presenting cell could make combined aOX40/aCTLA-4 therapy more effective. We administered an antibody-based vaccine targeting HER2 to the DEC-205 endocytic receptor on cross-presenting dendritic cells (anti-DEC-205/HER2; aDEC-205/HER2) and a potent adjuvant (poly (I:C)) to assist with maturation, along with aOX40/aCTLA-4 therapy. This therapy induced complete regression of established tumors and a pronounced infiltration of effector CD8 and CD4 T cells, with no effect on regulatory T cell infiltration compared to aOX40/aCTLA-4 alone. To be maximally effective, this therapy required expression of both OX40 and CTLA-4 on CD8 T cells. These data indicate that vaccination targeting cross-presenting dendritic cells with a tumor-associated antigen is a highly effective immunization strategy that can overcome some of the limitations of current systemic immunotherapeutic approaches that lack defined tumor-directed antigenic targets.

Linch|Stefanie N|SN|
Redmond|William L|WL|

Dendritic cell
Vaccine
Immunotherapy
CTLA-4
Checkpoint blockade
OX40
Anergy
Co-stimulation
Cytotoxic CD8 T cell
Tolerance


Doping in sport and exercise: anabolic, ergogenic, health and clinical issues.

Abstract: The use of doping agents is evident within competitive sport in senior and junior age groups, where they are taken by non-elite as well as elite participants. They are also taken in non-sporting contexts by individuals seeking to 'improve' their physique through an increase in muscle and/or decrease in fat mass. While attaining accurate data on the prevalence of their use has limitations, studies suggest the illicit use of doping agents by athletes and non-athletes may be 1-5% in the population and greater than 50% in some groups; with the prevalence being higher in males. There is conclusive evidence that some doping agents are anabolic and ergogenic. There is also evidence that the use of doping agents such as anabolic androgenic steroids, growth hormone and other anabolic agents, erythropoietin and stimulants conveys considerable health risks that include, but are not limited to: cardiovascular disease, diabetes, cancer, mental health issues, virilisation in females and the suppression of naturally produced androgens in males. This review will outline the anabolic, ergogenic and health impacts of selected doping agents and methods that may be used in both the sporting and physique development contexts. It also provides a brief tabulated overview of the history of doping and how doping agents may impact upon the analyses of clinical samples.

Bird|Stephen R|SR|
Goebel|Catrin|C|
Burke|Louise M|LM|
Greaves|Ronda F|RF|


Structural Variation of Prostate Urethra Reflected by the Ratio Between Prostate Volume and Prostatic Urethral Length is Associated with the Degrees of Lower Urinary Tract Symptoms.

Abstract:
OBJECTIVES
Because it is well known that the prostate volume is not directly associated with the degrees of lower urinary tract symptom (LUTS), we hypothesized that change of the prostatic urethra led by prostatic enlargement as missing links between them. To provide an integral description, we determined the ratio between prostate volume and prostatic urethral length (RPVL), and investigated its clinical implication.

METHODS
Prostate volume, prostatic urethral length, RPVL was measured from transrectal ultrasonography for 213 consecutive patients. The degree of LUTS was investigated using the international prostate symptom score (IPSS) and uroflowmetry, then the correlations were analyzed.

RESULTS
While no variables were significantly linked with total IPSS, obstructive symptoms (IPSS Q247) showed a negative association (r = -0.3, P < 0.001) and irritative symptoms (IPSS Q1356) showed a positive association solely with RPVL (r = 0.186, P = 0.007). These relevancies were enhanced (r = -0.471 [P = <0.001] and 0.3 [P = 0.004], respectively) in patients with a larger prostate (over 30 g, n = 93), but disappeared in their smaller counterparts (below 30 g, n = 120), (r = -0.133 [P = 0.143] and 0.75 [P = 0.410], respectively). In uroflowmetry, prostate urethral length showed positive correlation (r = 0.319 [P < 0.001]), and RPVL showed negative correlation (r = -0.195 [P = 0.004]) with post voiding residual amount, but these relationships similarly vanished in men with a smaller prostate.

CONCLUSIONS
The structural variation of the prostatic urethra within the prostate reflected by RPVL showed correlation with the degree of LUTS, with a tendency toward increasing prostatic urethra in obstructive and decreasing prostatic urethra in irritative symptoms, in men with a relatively large prostate.

prostate
urethra
lower urinary tract symptoms
ultrasonography