Salvinia natans: A potential test species for ecotoxicity testing.

Abstract: Although macrophytes are known to play vital roles in aquatic ecosystems, most quantitative aquatic toxicity data focus on fishes, water fleas, or algae, with limited ecotoxicity data published on macrophytes. Salvinia natans is a fast-growing plant commonly found in freshwater habitats. In this study, we verified a suitable disinfectant for preventing foreign contamination and formulated a culture medium for ensuring high productivity of S. natans. Finally, we established methodology for S. natans to be used in ecotoxicity testing of heavy metals and pesticides. As global regulations are being developed to harmonize guidelines and laboratory test species, S. natans is emerging as a potential candidate. The toxicity data publicly available for S. natans are very limited; hence, this study reports an advantageous culturing technique to optimize healthy growth of this species in the laboratory and presents optimal toxicity results, achieved by modifying the currently available test guidelines for Lemna. Our findings expand the currently limited range of test species for aquatic toxicity assays. We conclude that S. natans could serve as a valuable test species for aquatic toxicity assays.

Salvinia natans
Test species
Ecotoxicity
Metal
Pesticide


Investigating the prevalence, predictors, and prognosis of suboptimal statin use early after a non-ST elevation acute coronary syndrome.

Abstract:
BACKGROUND
High-potency statin therapy is recommended in the secondary prevention of cardiovascular disease but discontinuation, dose reduction, statin switching, and/or nonadherence occur in practice.

OBJECTIVES
To determine the prevalence and predictors of deviation from high-potency statin use early after a non-ST elevation acute coronary syndrome (NSTE-ACS) and its association with subsequent major adverse cardiovascular events (MACE) and all-cause mortality (ACM).

METHODS
A total of 1005 patients from a UK-based prospective NSTE-ACS cohort study discharged on high-potency statin therapy (atorvastatin 80 mg, rosuvastatin 20 mg, or 40 mg daily) were included. At 1 month, patients were divided into constant high-potency statin users, and suboptimal users incorporating statin discontinuation, dose reduction, switching statin to a lower equivalent potency, and/or statin nonadherence. Follow-up was a median of 16 months.

RESULTS
There were 156 suboptimal (∼15.5%) and 849 constant statin users. Factors associated in multivariable analysis with suboptimal statin occurrence included female sex (odds ratio 1.75, 95% confidence interval [CI] 1.14-2.68) and muscular symptoms (odds ratio 4.28, 95% CI 1.30-14.08). Suboptimal statin use was associated with increased adjusted risks of time to MACE (hazard ratio 2.10, 95% CI 1.25-3.53, P = .005) and ACM (hazard ratio 2.46, 95% CI 1.38-4.39, P = .003). Subgroup analysis confirmed that the increased MACE/ACM risks were principally attributable to statin discontinuation or nonadherence.

CONCLUSIONS
Conversion to suboptimal statin use is common early after NSTE-ACS and is partly related to muscular symptoms. Statin discontinuation or non-adherence carries an adverse prognosis. Interventions that preserve and enhance statin utilization could improve post NSTE-ACS outcomes.

Turner|Richard M|RM|
Yin|Peng|P|
Hanson|Anita|A|
FitzGerald|Richard|R|
Morris|Andrew P|AP|
Stables|Rod H|RH|
Jorgensen|Andrea L|AL|
Pirmohamed|Munir|M|

Statin
Cardiovascular
Discontinuation
Nonadherence
Mortality
Muscular symptoms


Nuclear-Overhauser-enhanced MR imaging of (31)P-containing metabolites: multipoint-Dixon vs. frequency-selective excitation.

Abstract: The purpose of this study is to develop nuclear-Overhauser-enhanced (NOE) [(1)H]-(31)P magnetic resonance imaging (MRI) based on 3D fully-balanced steady-state free precession (fbSSFP). Therefore, two implementations of a 3D fbSSFP sequence are compared using frequency-selective excitation (FreqSel) and multipoint-Dixon (MP-Dixon). (31)P-containing model solutions and four healthy volunteers were examined at field strengths of B0=3T and 7T. Maps of the distribution of phosphocreatine (PCr), inorganic phosphate (Pi), and adenosine 5´-triphosphate (ATP) in the human calf were obtained with an isotropic resolution of 1.5cm (1.0cm) in an acquisition time of 5min (10min). NOE-pulses had the highest impact on the PCr acquisitions enhancing the signal up to (82 ± 13) % at 3T and up to (37 ± 9) % at 7T. An estimation of the level of PCr in muscle tissue from [(1)H]-(31)P MRI data yielded a mean value of (33 ± 8) mM. In conclusion, direct [(1)H]-(31)P imaging using FreqSel as well as MP-Dixon is possible in clinically feasible acquisition times. FreqSel should be preferred for measurements where only a single metabolite resonance is considered. MP-Dixon performs better in terms of SNR if a larger spectral width is of interest.

Rink|Kristian|K|
Berger|Moritz C|MC|
Korzowski|Andreas|A|
Breithaupt|Mathies|M|
Biller|Armin|A|
Bachert|Peter|P|
Nagel|Armin M|AM|

(31)P MRI
Dixon
High-energy phosphate metabolism
Nuclear Overhauser effect
Steady-state free precession (SSFP)


Levodopa Positively Affects Neovascular Age-Related Macular Degeneration.

Abstract:
BACKGROUND
Age-related macular degeneration (AMD) is a common cause of blindness worldwide. Neovascular AMD (nAMD) is an advanced form of the disease, in which excess vascular endothelial growth factor (VEGF) induces growth of new blood vessels that leak fluid, accounting for 90% of vision loss in AMD. Dysfunction of the retinal pigment epithelium likely initiates AMD. Retinal pigment epithelial cells express a G protein-coupled receptor, GPR143, which downregulates VEGF in response to levodopa. Anti-VEGF therapy effectively treats nAMD, suggesting that excessive VEGF activity drives the pathology.

METHODS
In an open-label pilot study, in patients with newly diagnosed nAMD and naïve to anti-VEGF injections (Cohort-1), the effects of carbidopa-levodopa on vision and anatomic outcomes were evaluated for 4 weeks. Then patients were followed 5 months further with ascending levodopa doses. Patients previously treated with anti-VEGF injection therapy (Cohort-2) were also treated with ascending levodopa doses and evaluated for 6 months.

RESULTS
Levodopa was safe, well tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29% (P = .02, n = 12) without anti-VEGF treatment. Through 6 months the decrease in retinal fluid was sustained, with a mean frequency of 0.38 injections/month. At month 6, mean visual acuity improved by 4.7 letters in Cohort-1 (P = .004, n = 15) and by 4.8 letters in Cohort-2 (P = .02, n = 11). Additionally, there was a 52% reduction in the need for anti-VEGF injections in Cohort-2 (P = .002).

CONCLUSIONS
Our findings suggest efficacy and support the pharmacological targeting of GPR143 with levodopa for the treatment of nAMD in future studies.

Figueroa|Anna G|AG|
Boyd|Brennan M|BM|
Christensen|Cory A|CA|
Javid|Cameron G|CG|
McKay|Brian S|BS|
Fagan|Timothy C|TC|
Snyder|Robert W|RW|

Age-related macular degeneration (AMD)
Neovascular AMD
nAMD
Retinal pigment epithelium
GPR143
Carbidopa-levodopa
L-DOPA
Prospective study
Wet AMD


Impact of culture on autobiographical life structure in depression.

Abstract:
OBJECTIVES
Distortions in autobiographical memory have been implicated in major depressive disorder (MDD). Those with MDD demonstrate a 'depressogenic' autobiographical life structure. Research has not examined how culture influences this process. We investigated whether Malay individuals (members of an interdependent culture) with MDD demonstrated a 'depressogenic' autobiographical life structure similar to that of British individuals (members of an independent culture) with MDD.

DESIGN
A 2 (Culture; Malay, British) × 2 (Mood; depressed, control) cross-sectional design using a card sort task and self-report measures was used.

METHODS
Malay individuals with MDD or no history of MDD completed the life-structure card-sorting task, which provided a novel method for investigating organizational structure of the life narrative. These data were compared to previously collected data in which British individuals with MDD or without MDD had completed the same task within the same experimental protocol.

RESULTS
Pan-culturally those with MDD had greater negativity (i.e., used more negative attributes), negative redundancy (i.e., used the same negative attributes repeatedly across life chapters) and negative emodiversity (i.e., had greater variety and relative abundance of negative attributes), and reduced positive redundancy (i.e., used the same positive attributes repeatedly across chapters) in their structuring relative to controls. While the British MDD group had greater compartmentalization (i.e., the negative and positive attributes were clustered separately across different chapters) than British controls, the Malay MDD group had lower levels of compartmentalization than Malay controls.

CONCLUSIONS
The findings suggest culture may shape aspects of the autobiographical life structure in MDD.

PRACTITIONER POINTS
The majority of the literature investigating depression pertains to individuals from European Western cultures, despite recognition that depression ranks as one of the most debilitating diseases worldwide. This raises questions as to whether current depression models and interventions can be applied universally or whether they are limited to European Western groups. The current study found that pan-culturally those with MDD had similar structuring of their life story relative to controls. However, there were some cultural differences that need to be considered (e.g., Malay individuals provided less detailed, less elaborate and less emotionally diverse life stories and while the British MDD group had greater compartmentalization than British controls, the Malay MDD group had lower levels of compartmentalization than Malay controls). Limitations of the study included group differences in gender and mood at the time of testing. Cultural differences in the number of attributes used may have influenced findings. Only the Malay group completed the individualism-collectivism measure.

culture
life structure
depression
autobiographical memory


Impact of synovial fluid flow on temperature regulation in knee cartilage.

Abstract: Several studies have reported an increase of temperature in cartilage submitted to cyclic sinusoidal loading. The temperature increase is in part due to the viscous behavior of this tissue, which partially dissipates the input mechanical energy into heat. While the synovial fluid flow within the intra-articular gap and inside the porous cartilage is supposed to play an important role in the regulation of the cartilage temperature, no specific study has evaluated this aspect. In the present numerical study, a poroelastic model of the knee cartilage is developed to evaluate first the temperature increase in the cartilage due to dissipation and second the impact of the synovial fluid flow in the cartilage heat transfer phenomenon. Our results showed that, the local temperature is effectively increased in knee cartilage due to its viscous behavior. The synovial fluid flow cannot significantly preventing this phenomenon. We explain this result by the low permeability of cartilage and the moderate fluid exchange at the surface of cartilage under deformation.

Moghadam|Mohamadreza Nassajian|MN|
Abdel-Sayed|Philippe|P|
Camine|Valérie Malfroy|VM|
Pioletti|Dominique P|DP|

Synovial fluid
Cartilage
Dissipation
Heat
Poroelasticity


Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies.

Abstract: Atherogenesis, the formation of atherosclerotic plaques, is a complex process that involves several mechanisms, including endothelial dysfunction, neovascularization, vascular proliferation, apoptosis, matrix degradation, inflammation, and thrombosis. The pathogenesis and progression of atherosclerosis are explained differently by different scholars. One of the most common theories is the destruction of well-balanced homeostatic mechanisms, which incurs the oxidative stress. And oxidative stress is widely regarded as the redox status realized when an imbalance exists between antioxidant capability and activity species including reactive oxygen (ROS), nitrogen (RNS) and halogen species, non-radical as well as free radical species. This occurrence results in cell injury due to direct oxidation of cellular protein, lipid, and DNA or via cell death signaling pathways responsible for accelerating atherogenesis. This paper discusses inflammation, mitochondria, autophagy, apoptosis, and epigenetics as they induce oxidative stress in atherosclerosis, as well as various treatments for antioxidative stress that may prevent atherosclerosis.

Yang|Xinyu|X| Li|Yang|Y| Li|Yanda|Y| Ren|Xiaomeng|X| Zhang|Xiaoyu|X| Hu|Dan|D| Gao|Yonghong|Y| Xing|Yanwei|Y| Shang|Hongcai|H|

atherosclerosis
therapies
apoptosis
inflammation
oxidative stress
mitochondria
autophagy
epigenetics


Translating research into clinical practice: quality improvement to halve non-adherence to methotrexate.

Abstract:
OBJECTIVE
MTX remains the cornerstone for therapy for RA, yet research shows that non-adherence is significant and correlates with response to therapy. This study aimed to halve self-reported non-adherence to MTX at the Kellgren Centre for Rheumatology.

METHODS
An anonymous self-report adherence questionnaire was developed and data collected for 3 months prior to the introduction of interventions, and then regularly for the subsequent 2.5 years. A series of interventions were implemented, including motivational interviewing training, consistent information about MTX and development of a summary bookmark. Information on clinic times was collected for consultations with and without motivational interviewing. Surveys were conducted to ascertain consistency of messages about MTX. A biochemical assay was used to test MTX serum levels in patients at two time points: before and 2.8 years following introduction of the changes. Remission rates at 6 and 12 months post-MTX initiation were retrieved from patient notes and cost savings estimated by comparing actual numbers of new biologic starters compared with expected numbers based on the numbers of consultants employed at the two time points.

RESULTS
Between June and August 2016, self-reported non-adherence to MTX was 24.7%. Following introduction of the interventions, self-reported non-adherence rates reduced to an average of 7.4% between April 2018 and August 2019. Clinic times were not significantly increased when motivational interviewing was employed. Consistency of messages by staff across three key areas (benefits of MTX, alcohol guidance and importance of adherence) improved from 64% in September 2016 to 94% in January 2018. Biochemical non-adherence reduced from 56% (September 2016) to 17% (June 2019), whilst remission rates 6 months post-initiation of MTX improved from 13% in 2014/15 to 37% in 2017/18, resulting is estimated cost savings of £30 000 per year.

CONCLUSION
Non-adherence to MTX can be improved using simple measures including focussing on the adherence and the benefits of treatment, and providing consistent information across departments.

Barton|Anne|A| Jani|Meghna|M| Bundy|Christine|C| Bluett|James|J| McDonald|Stephen|S| Keevil|Brian|B| Dastagir|Faraz|F| Aris|Melissa|M| Bruce|Ian|I| Ho|Pauline|P| McCarthy|Eoghan|E| Bruce|Ellen|E| Parker|Ben|B| Hyrich|Kimme|K| Gorodkin|Rachel|R|

D018501:Antirheumatic Agents
D001172:Arthritis, Rheumatoid
D001688:Biological Products
D003253:Consultants
D017046:Cost Savings
D006801:Humans
D055118:Medication Adherence
D008727:Methotrexate
D062405:Motivational Interviewing
D010353:Patient Education as Topic
D058996:Quality Improvement
D012074:Remission Induction
D057566:Self Report
D011795:Surveys and Questionnaires
D013997:Time Factors

quality improvement
methotrexate
adherence
motivational interviewing


Morgagni hernia - case reports.

Abstract: Morgagni hernia is a rare form of diaphragmatic hernia. It is a congenital defect of the diaphragm, often asymptomatic in adulthood and thus usually found only incidentally. Its treatment is predominantly surgical. This article presents three case reports of patients operated in our department.

Švejdová|A|A| Třeška|V|V| Šafránek|J|J| Geiger|J|J| Bejček|J|J|


On the use of microwave pretreatment to assist zero-waste chemical-free production process of nanofibrillated cellulose from lime residue.

Abstract: Microwave (MW) pretreatment as an energy-efficient method to enhance the production of nanofibrillated cellulose (NFC) from lime (Citrus aurantifolia Swingle) residue after juice extraction is proposed. NFC was prepared by subjecting lime residue to MW pretreatment for up to 3 rounds; this was followed by high-shear and high-pressure homogenization. Repeated application of MW pretreatment helped remove non-cellulosic components and resulted in an increased cellulose content and crystallinity index but a decrease in fiber diameter. Freshly prepared NFC sample exhibited gel-like behavior. G' and G″ of suspension prepared from dried NFC markedly decreased, indicating the loss of gel-like property upon drying. Proper pectin molecular weight as well as pectin content were noted to play an important role in controlling aggregation of NFC during drying and hence water redispersibility of dried NFC. Significant amounts of pectin and limonin could be recovered and utilized as co-products after the first round of MW pretreatment.

Crystallinity
Pectin
Limonin
Microstructure
Viscoelastic property


Efficacy of repeat hepatectomy for recurrence following curative hepatectomy for colorectal liver metastases: A Retrospective Cohort Study of 128 patients.

Abstract:
BACKGROUND
Despite improvements in surgery and chemotherapy, most patients develop recurrence after initial hepatectomy for colorectal liver metastasis (CRLM). Following initial hepatectomy for CRLM, patterns and surgical management of recurrence have not been widely reported.

MATERIALS AND METHODS
We identified 128 patients who underwent hepatic resection for CRLM between January 2000 and December 2012. Demographics, operative data, site of recurrence, and long-term survival data were collected and analyzed. Patients were stratified into 3 groups based on their site of recurrence as intrahepatic, intra- and extrahepatic, and extrahepatic. In addition, the influence of potential factors on overall survival (OS) in patients with only liver relapse was analyzed through univariate and multivariate analysis.

RESULTS
After curative initial hepatectomy, 87 (68.0%) patients had a recurrence: 33 in the intrahepatic group, 11 in the intra- and extrahepatic group, and 43 in the extrahepatic group. The OS for the intra- and extrahepatic group was significantly lower than that for the intrahepatic group. In the intrahepatic group, disease-free interval (DFI) < 12 months and non-repeat hepatectomy were independent poor prognostic factors. Carcinoembryonic antigen (CEA) at the time of hepatectomy was significantly higher in DFI < 12 group than in the DFI ≥ 12 group.

CONCLUSION
Patterns of recurrence following initial hepatectomy for CRLM have important implications for OS. In the intrahepatic recurrence group, short DFI was correlated with high CEA at hepatectomy, and was a poor prognostic factor.

Hashimoto|Masakazu|M| Kobayashi|Tsuyoshi|T| Ishiyama|Kohei|K| Ide|Kentaro|K| Ohira|Masahiro|M| Tahara|Hiroyuki|H| Kuroda|Shintaro|S| Hamaoka|Michinori|M| Iwako|Hiroshi|H| Okimoto|Masashi|M| Ohdan|Hideki|H|

Repeat hepatectomy
Recurrence
Colorectal liver metastases
Prognostic factor


Hydroxylation, Epoxidation, and Dehydrogenation of Capsaicin by a Microbial Promiscuous Cytochrome P450 105D7.

Abstract: Cytochrome P450 enzymes (P450s) are versatile biocatalysts, which insert a molecular oxygen into inactivated C-H bonds under mild conditions. CYP105D7 from Streptomyces avermitilis has been reported as a bacterial substrate-promiscuous P450 which catalyzes the hydroxylation of 1-deoxypentalenic acid, diclofenac, naringenin, compactin and steroids. In this study, CYP105D7 catalyzes hydroxylation, epoxidation and dehydrogenation of capsaicin, a pharmaceutical agent, revealing its functional diversity. The kinetic parameters of the CYP105D7 oxidation of capsaicin were determined as Km =311.60±87.30 μM and kcat =2.01±0.33 min-1 . In addition, we conducted molecular docking, mutagenesis and substrate binding analysis, indicating that Arg81 plays crucial role in the capsaicin binding and catalysis. To our best knowledge, this study presents the first report to illustrate that capsaicin can be catalyzed by prokaryotic P450s.

hydroxylation epoxidation dehydrogenation capsaicin P450s bioconversion


Adolescents who binge eat and drink: The role of emotion regulation.

Abstract: This cross-sectional study examined binge eating and binge drinking behaviors exploring their association with the strategies of Emotion Regulation, such as Cognitive Reappraisal (CR) and Expression Suppression (ES). The sample consisted of 1004 Italian students (395 males and 609 females) attending high school. The average age of the students was 17.9 years (SD =0.8; range: 16-21). They completed self-report measures assessing binge behaviors and Emotion Regulation strategies. No differences resulted between adolescents assuming binge behaviors and no bingers as regards CR; conversely, adolescents engaging in binge eating and in both binge behaviors reported the highest levels of ES. Furthermore, both Emotion Regulation strategies were significant predictors of binge eating. The present study suggested that binge behaviors were strongly associated with adolescent's ability to evaluate and manage their emotions, so that adolescents may benefit from more precise and specific prevention and treatment approaches focused on training to use more adaptive and effective strategies to regulate their emotions.

adolescence
Binge eating
emotion regulation
binge drinking


Coronary physiologic assessment based on angiography and intracoronary imaging.

Abstract: Despite the current evidence supporting clinical benefits of fractional flow reserve (FFR), its uptake in the cardiac catheterization laboratory has been slow due to procedural cost and increased time with the need for maximum hyperemia. Recently, novel physiological indices derived from coronary angiography and intracoronary imaging have emerged to overcome issues with a wire-based FFR. Angiography-based FFR can be measured without vessel instrumentation and has shown excellent diagnostic performance using wire-based FFR as the reference standard. Thus, angiography-based FFR may facilitate coronary functional assessment before and after percutaneous coronary intervention (PCI). Angiography-based index of microcirculatory resistance (IMR) is another new computational index for assessing the coronary microcirculation. Although angiography-derived IMR remains in an early phase of development and requires further validation, its less-invasive nature may help broaden the adoption of microvascular functional assessment in various conditions such as myocardial infarction and cardiac allograft vasculopathy. Lastly, computational FFR based on intravascular ultrasound and optical coherence tomography allows detailed lesion assessment from both morphological and functional standpoints. Given a growing interest in physiology-guided PCI optimization strategies, intravascular imaging-based FFR may become the main assessment tool to confirm successful PCI.

Takahashi|Tatsunori|T| Theodoropoulos|Kleanthis|K| Latib|Azeem|A| Okura|Hiroyuki|H| Kobayashi|Yuhei|Y|

Fractional flow reserve
Coronary angiography
Functional assessment
Microcirculation
Intravascular ultrasound
Optical coherence tomography


Cross-Genome Clustering of Human and C. elegans G-Protein Coupled Receptors.

Abstract: G-protein coupled receptors (GPCRs) are one of the largest groups of membrane proteins and are popular drug targets. The work reported here attempts to perform cross-genome phylogeny on GPCRs from two widely different taxa, human versus C. elegans genomes and to address the issues on evolutionary plasticity, to identify functionally related genes, orthologous relationship, and ligand binding properties through effective bioinformatic approaches. Through RPS blast around 1106 nematode GPCRs were given chance to associate with previously established 8 types of human GPCR profiles at varying E-value thresholds and resulted 32 clusters were illustrating co-clustering and class-specific retainsionship. In the significant thresholds, 81% of the C. elegans GPCRs were associated with 32 clusters and 27 C. elegans GPCRs (2%) inferred for orthology. 177 hypothetical proteins were observed in cluster association and could be reliably associated with one of 32 clusters. Several nematode-specific GPCR clades were observed suggesting lineage-specific functional recruitment in response to environment.

Nagarathnam|Balasubramanian|B| Kalaimathy|Singaravelu|S| Balakrishnan|Veluchamy|V| Sowdhamini|Ramanathan|R|

cross-genome clustering
phylogeny
G-protein-coupled receptors (GPCRs)
PSSM profile
serpentine receptors


Non-surgical factors influencing lymph node yield in colon cancer.

Abstract: There are numerous factors which can affect the lymph node (LN) yield in colon cancer specimens. The aim of this paper was to identify both modifiable and non-modifiable factors that have been demonstrated to affect colonic resection specimen LN yield and to summarise the pertinent literature on these topics. A literature review of PubMed was performed to identify the potential factors which may influence the LN yield in colon cancer resection specimens. The terms used for the search were: LN, lymphadenectomy, LN yield, LN harvest, LN number, colon cancer and colorectal cancer. Both non-modifiable and modifiable factors were identified. The review identified fifteen non-surgical factors: (13 non-modifiable, 2 modifiable) which may influence LN yield. LN yield is frequently reduced in older, obese patients and those with male sex and increased in patients with right sided, large, and poorly differentiated tumours. Patient ethnicity and lower socioeconomic class may negatively influence LN yield. Pre-operative tumour tattooing appears to increase LN yield. There are many factors that potentially influence the LN yield, although the strength of the association between the two varies greatly. Perfecting oncological resection and pathological analysis remain the cornerstones to achieving good quality and quantity LN yields in patients with colon cancer.

Factors
Lymph node
Yield
Colon cancer
Number


Two Compasses in the Central Complex of the Locust Brain.

Abstract: Many migratory insects rely on a celestial compass for spatial orientation. Several features of the daytime sky, all generated by the sun, can be exploited for navigation. Two of these are the position of the sun and the pattern of polarized skylight. Neurons of the central complex (CX), a group of neuropils in the central brain of insects, have been shown to encode sky compass cues. In desert locusts, the CX holds a topographic, compass-like representation of the plane of polarized light (E-vector) presented from dorsal direction. In addition, these neurons also encode the azimuth of an unpolarized light spot, likely representing the sun. Here, we investigate whether, in addition to E-vector orientation, the solar azimuth is represented topographically in the CX. We recorded intracellularly from eight types of CX neuron while stimulating animals of either sex with polarized blue light from zenithal direction and an unpolarized green light spot rotating around the animal's head at different elevations. CX neurons did not code for elevation of the unpolarized light spot. However, two types of columnar neuron showed a linear correlation between innervated slice in the CX and azimuth tuning to the unpolarized green light spot, consistent with an internal compass representation of solar azimuth. Columnar outputs of the CX also showed a topographic representation of zenithal E-vector orientation, but the two compasses were not linked to each other. Combined stimulation with unpolarized green and polarized blue light suggested that the two compasses interact in a nonlinear way.SIGNIFICANCE STATEMENT In the brain of the desert locust, neurons sensitive to the plane of celestial polarization are arranged like a compass in the slices of the central complex (CX). These neurons, in addition, code for the horizontal direction of an unpolarized light cue possibly representing the sun. We show here that horizontal directions are, in addition to E-vector orientations from the dorsal direction, represented in a compass-like manner across the slices of the CX. However, the two compasses are not linked to each other, but rather seem to interact in a cell-specific, nonlinear way. Our study confirms the role of the CX in signaling heading directions and shows that different cues are used for this task.

central complex
navigation
sky compass
head direction
insect brain
polarization vision


Risk Factors Associated With Invasive Fungal Infections in Kidney Transplant Patients.

Abstract:
BACKGROUND
Kidney transplant recipients are at increased risk for developing invasive fungal infections (IFI). We queried the United States Renal Data System (USRDS) for risk factors for IFI in these patients.

METHODS
Patients who underwent a kidney transplant between 2005 and 2008 were queried for an IFI diagnosis using ICD-9 codes. An IFI was defined as at least one documented diagnosis from one of the following: (1) Candida (candidemia); (2) Histoplasmosis; (3) Aspergillosis; (4) Cryptococcosis; (5) "Other" mycoses. Potential risk factors included demographics, certain comorbidities and immunosuppressive medications. To examine the relative risk (RR), simple bivariate models were used, followed by a comprehensive full model to estimate the adjusted RR (aRR).

RESULTS
Of 57,188 kidney transplant patients, 1,218 had 1,343 IFI diagnoses, with a median time to infection of 495 days. "Other" mycoses accounted for the most IFI diagnoses (37%), followed by aspergillosis (22%). The risk for any IFI was increased with age ≥65 years. Diabetes (aRR = 1.71), bacterial pneumonia (aRR = 1.62) and UTI (aRR = 1.34) were the top 3 clinical risk factors for infection. Each of the IFI groups was also associated with individual risk factors. Therapy with mycophenolate mofetil was associated with a decreased risk of candidemia.

CONCLUSIONS
Risk factors for IFI in renal transplant patients include demographic, medication-associated and clinical data, as well as organism-specific factors. These results offer an extensive clinical profile of risk for IFI, and may thus help inform the diagnosis and presumptive therapy of invasive fungal infections in renal transplant recipients.

Leitheiser|Sara|S|
Harner|Andrew|A|
Waller|Jennifer L|JL|
Turrentine|Jake|J|
Baer|Stephanie|S|
Kheda|Mufaddal|M|
Nahman|N Stanley|NS|
Colombo|Rhonda E|RE|

Risk factors
Invasive fungal infection
Infections
Kidney transplantation


Protective effect of gelatin polypeptides from Pacific cod (Gadus macrocephalus) against UV irradiation-induced damages by inhibiting inflammation and improving transforming growth factor-β/Smad signaling pathway.

Abstract: Exposure to ultraviolet (UV) radiation results in skin damage, collagen reduction in the dermis, and consequently, premature skin aging (photoaging). The goal of this study was to examine the effect of gelatin hydrolysate (CH) from pacific cod (Gadus macrocephalus) skin on UV irradiation-induced inflammation and collagen reduction of photoaging mouse skin. The effect of CH on the activities of endogenous antioxidant enzymes was investigated. The expressions of nuclear factor-κB (NF-κB), proinflammatory cytokines, type I and type III procollagen, transforming growth factor-β1 (TGF-β1), type II receptor of TGF-β1 (TGF-βRII), and Smad7 were determined using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. The results showed that oral administration of CH suppressed UV irradiation-induced damages to skin by inhibiting the depletion of endogenous antioxidant enzyme activity, and by suppressing the expression of NF-κB as well as NF-κB-mediated proinflammatory cytokines expression. Furthermore, CH inhibited type I procollagen synthesis reduction by up-regulating TβRII level and down-regulating Smad7 level, which demonstrates that CH is involved in matrix collagen synthesis by activating the TGF-β/Smad pathway in the photoaging skin. Based on these results, we conclude that CH protected skin from UV irradiation-induced photodamages, and CH may be a potentially effective agent for the prevention of photoaging.

D000077294:Receptor, Transforming Growth Factor-beta Type II

D018125:Receptors, Transforming Growth Factor beta

Pacific cod
Photoaging
Gelatin hydrolysate
Antioxidant enzymes
TGF-β/Smad pathway
Inflammatory cytokines


Development and validation of a high-throughput transcriptomic biomarker to address 21st century genetic toxicology needs.

Abstract: Interpretation of positive genotoxicity findings using the current in vitro testing battery is a major challenge to industry and regulatory agencies. These tests, especially mammalian cell assays, have high sensitivity but suffer from low specificity, leading to high rates of irrelevant positive findings (i.e., positive results in vitro that are not relevant to human cancer hazard). We developed an in vitro transcriptomic biomarker-based approach that provides biological relevance to positive genotoxicity assay data, particularly for in vitro chromosome damage assays, and propose its application for assessing the relevance of the in vitro positive results to carcinogenic hazard. The transcriptomic biomarker TGx-DDI (previously known as TGx-28.65) readily distinguishes DNA damage-inducing (DDI) agents from non-DDI agents. In this study, we demonstrated the ability of the biomarker to classify 45 test agents across a broad set of chemical classes as DDI or non-DDI. Furthermore, we assessed the biomarker's utility in derisking known irrelevant positive agents and evaluated its performance across analytical platforms. We correctly classified 90% (9 of 10) of chemicals with irrelevant positive findings in in vitro chromosome damage assays as negative. We developed a standardized experimental and analytical protocol for our transcriptomics biomarker, as well as an enhanced application of TGx-DDI for high-throughput cell-based genotoxicity testing using nCounter technology. This biomarker can be integrated in genetic hazard assessment as a follow-up to positive chromosome damage findings. In addition, we propose how it might be used in chemical screening and assessment. This approach offers an opportunity to significantly improve risk assessment and reduce cost.

Li|Heng-Hong|HH|
Chen|Renxiang|R|
Hyduke|Daniel R|DR|
Williams|Andrew|A|
Frötschl|Roland|R|
Ellinger-Ziegelbauer|Heidrun|H|
O'Lone|Raegan|R|
Yauk|Carole L|CL|
Aubrecht|Jiri|J|
Fornace|Albert J|AJ|0000-0001-9695-085X

transcriptomic biomarker
genotoxicity
TGx-DDI
DNA damage response
high-throughput screening


Haemophilus influenzae responds to glucocorticoids used in asthma therapy by modulation of biofilm formation and antibiotic resistance.

Abstract: Glucocorticosteroids are used as a main treatment to reduce airway inflammation in people with asthma who suffer from neutrophilic airway inflammation, a condition frequently associated with Haemophilus influenzae colonization. Here we show that glucocorticosteroids have a direct influence on the behavior of H. influenzae that may account for associated difficulties with therapy. Using a mouse model of infection, we show that corticosteroid treatment promotes H. influenzae persistence. Transcriptomic analysis of bacteria either isolated from infected mouse airway or grown in laboratory medium identified a number of genes encoding regulatory factors whose expression responded to the presence of glucocorticosteroids. Importantly, a number of these corticosteroid-responsive genes also showed elevated expression in H. influenzae within sputum from asthma patients undergoing steroid treatment. Addition of corticosteroid to H. influenzae led to alteration in biofilm formation and enhanced resistance to azithromycin, and promoted azithromycin resistance in an animal model of respiratory infection. Taken together, these data strongly suggest that H. influenzae can respond directly to corticosteroid treatment in the airway potentially influencing biofilm formation, persistence and the efficacy of antibiotic treatment.

Earl|Chris S|CS|
Keong|Teh Wooi|TW|
An|Shi-qi|SQ|
Murdoch|Sarah|S|
McCarthy|Yvonne|Y|
Garmendia|Junkal|J|
Ward|Joseph|J|
Dow|J Maxwell|JM|
Yang|Liang|L|
O'Toole|George A|GA|
Ryan|Robert P|RP|

Haemophilus influenzae
asthma
biofilm
antibiotic resistance
steroids


Sexual Attraction and Falling in Love in Persons with Pedohebephilia.

Abstract: Few studies of pedophilia or hebephilia have included questions about romantic attraction. We conducted an anonymous online survey of 306 men who self-reported as sexually attracted to children. The majority (72%) of participants reported they had fallen in love with a child in their lifetime. Participants reported greater feelings of attachment to children than feelings of infatuation. Though sexual attraction and falling in love were strongly correlated, they were not synonymous. Participants who reported pedohebephilia (defined in this study as attraction to prepubescent and pubescent children) were more likely to have fallen in love with a child than participants who reported pedohebe-ephebophilia (defined as attraction to prepubescent, pubescent, and post-pubescent minors). Also, participants with an exclusive attraction to children were more likely to have fallen in love with a child than participants who were equally attracted to children and adults. The results of this study were consistent with the suggestion of Seto (2012) that pedohebephilia could be considered a form of sexual orientation for age, which includes both sexual and romantic attraction.

Pedohebephilia
Pedophilia
Romantic attraction
Sexual orientation
DSM-5


De Novo Valve Tissue Morphology Following Bioscaffold Mitral Valve Replacement in a Juvenile Non-Human Primate Model.

Abstract: The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; n = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve's annulus region (p < 0.05) at 3 months compared to the 11- and 20-month explants, there were no other significant differences (p > 0.05) found between any of the other principal valve ECM components (collagen and elastin) at the leaflet, annulus, or chordae tendinea locations, across these time points. In particular, neochordae tissue had formed, which seamlessly integrated with the native papillary muscles. However, additional processing will be required to trigger accelerated, uniform and complete valve ECM formation in the recipient. Regardless of the specific processing done to the bioscaffold valve, in this proof-of-concept study, we estimate that a 3-month window following bioscaffold valve replacement is the timeline in which complete regeneration of the valve and integration with the host needs to occur.

Gonzalez|Brittany A|BA|
Perez Gonzalez|Marcos|M|
Scholl|Frank|F|0000-0002-3084-3012
Bibevski|Steven|S|
Ladich|Elena|E|
Bibevski|Jennifer|J|
Morales|Pablo|P|
Lopez|Jesus|J|
Casares|Mike|M|
Brehier|Vincent|V|
Hernandez|Lazaro|L|
Ramaswamy|Sharan|S|0000-0003-4108-7141


Genomic and transcriptomic characterization of Pseudomonas aeruginosa small colony variants derived from a chronic infection model.

Abstract: Phenotypic change is a hallmark of bacterial adaptation during chronic infection. In the case of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis, well-characterized phenotypic variants include mucoid and small colony variants (SCVs). It has previously been shown that SCVs can be reproducibly isolated from the murine lung following the establishment of chronic infection with mucoid P. aeruginosa strain NH57388A. Using a combination of single-molecule real-time (PacBio) and Illumina sequencing we identify a large genomic inversion in the SCV through recombination between homologous regions of two rRNA operons and an associated truncation of one of the 16S rRNA genes and suggest this may be the genetic switch for conversion to the SCV phenotype. This phenotypic conversion is associated with large-scale transcriptional changes distributed throughout the genome. This global rewiring of the cellular transcriptomic output results in changes to normally differentially regulated genes that modulate resistance to oxidative stress, central metabolism and virulence. These changes are of clinical relevance because the appearance of SCVs during chronic infection is associated with declining lung function.

Irvine|Sharon|S|
Bunk|Boyke|B|
Bayes|Hannah K|HK|
Spröer|Cathrin|C|
Connolly|James P R|JPR|
Six|Anne|A|
Evans|Thomas J|TJ|
Roe|Andrew J|AJ|
Overmann|Jörg|J|
Walker|Daniel|D|

D015964:Gene Expression Regulation, Bacterial

transcriptomics
Pseudomonas aeruginosa
small colony variants
chronic infection
recombination


Donor-Derived Transmission of Cryptococcus gattii sensu lato in Kidney Transplant Recipients.

Abstract: We describe cases of donor-derived transmission of Cryptococcus deuterogattii in 2 kidney transplant recipients in Brazil and published information on other cases. Prompt reduction of immunosuppression and initiation of antifungal therapy was required to successfully control the fungal infections and preserve engraftment.

Santos|Daniel W C L|DWCL|
Hagen|Ferry|F|
Meis|Jacques F|JF|
Cristelli|Marina P|MP|
Viana|Laila A|LA|
Bernardi|Fabiola D C|FDC|
Tedesco-Silva|Hélio|H|
Medina-Pestana|José O|JO|
Colombo|Arnaldo L|AL|

Cryptococcus gattii
kidney transplantation
Brazil
immunosuppression
Antifungal therapy
fungal infection
HIV/AIDS and other retroviruses
donor-transmitted disease
fungi


Increased Tissue Expression of Lectin-Like Oxidized LDL Receptor-1 (LOX-1) Is Associated with Disease Severity in Chronic Rhinosinusitis with Nasal Polyps.

Abstract:
BACKGROUND
The oxidative stress, induced by both environmental and intrinsic stimuli, underlies the onset and persistency of chronic rhinosinusitis (CRS). Scavenger receptors (SRs) are a broad family of transmembrane receptors involved in a dysfunctional host-environment interaction through a reaction with reactive oxygen species (ROS) production.

OBJECTIVE
We hypothesized possible roles of two major SRs in CRS pathology that can translate to clinical phenotypes or histological subtypes: lectin-like oxidized low-density lipoproteins (LDL) receptor-1 (LOX-1) and scavenger receptor class B type 1 (SR-B1).

PATIENTS AND METHODS
We collected ethmoid sinus mucosa specimens and blood samples from patients with CRS with nasal polyps (CRSwNP; n = 31) or CRS without NP (CRSsNP; n = 13) and 19 control subjects. We performed an RT-PCR analysis, ELISA assay, and immunostaining to determine the expressions and distributions of LOX-1 and SR-B1.

RESULTS
The CRSwNP group showed a significant increase in LOX-1 mRNA expression compared to the control group. There was no significant difference in SR-B1 mRNA levels among the three groups. The LOX-1 mRNA levels were positively correlated with the sinus computed tomography (CT) scores. Sinus tissue, but not serum samples, showed elevated concentrations of LOX-1 protein in the CRSwNP group versus the control group. The LOX-1 protein distribution was localized in inflammatory cells and vascular endothelial cells.

CONCLUSION
LOX-1 is a major receptor for oxidized low-density lipoprotein produced by oxidative stress. This is the first study to report alterations in LOX-1 expression and production triggered by persistent inflammatory processes in CRSwNP patients. Our findings reveal complex but important roles for SRs that may contribute to the onset of different CRS phenotypes.

Nishida|Manabu|M| Takeno|Sachio|S|0000-0002-9853-2501 Takemoto|Kohta|K| Takahara|Daisuke|D| Hamamoto|Takao|T| Ishino|Takashi|T| Kawasumi|Tomohiro|T|

chronic rhinosinusitis with nasal polyps


Recession-resection surgery augmented with botulinum toxin a chemodenervation for paralytic horizontal strabismus.

Abstract: In this case series study, we assessed the effects of recession-resection surgery augmented with botulinum toxin A chemodenervation for patients with chronic paralytic horizontal strabismus. In addition, we compared these effects with those of full tendon transposition (FTT) augmented with posterior intermuscular suture (PIMS). Ten patients who underwent strabismus surgery due to paralytic horizontal strabismus were retrospectively reviewed. They received a recession-resection surgery augmented with botulinum toxin A chemodenervation (type I surgery) or a FTT augmented with PIMS (type II surgery). The preoperative angle of deviation (AOD) and postoperative improvement in AOD were compared according to the type of procedure. The preoperative AOD was 60.00 ± 28.50 prism diopters (PD) for type I surgery and 68.00 ± 27.06 PD for type II (p = 0.421). Improvement in AOD was 53.20 ± 25.01 PD for type I surgery and 44.20 ± 18.74 PD for type II (p = 0.548). Recession-resection surgery augmented with botulinum toxin A chemodenervation is a concise and effective procedure for treating paralytic horizontal strabismus.

Kim|Eun-Ji|EJ|
Hong|Samin|S|
Lee|Jong Bok|JB|
Han|Sueng-Han|SH|

Recession-resection surgery
Botulinum toxins type A
Paralytic strabismus


A generalized dose-response relationship for adenovirus infection and illness by exposure pathway.

Abstract: Adenoviruses are found everywhere in the environment, and cause various health problems including symptoms of enteric illness, and respiratory illness. Despite their significance to public health, few studies have addressed the health risks associated with exposure to adenovirus. Human challenge studies have been published for a few adenoviruses, which involved exposure through oral ingestion, inhalation, intranasal and intraocular droplet inoculation. Nothwithstanding the different symptoms resulting from such exposures, infection can be defined as colonization of a corresponding mucosa. A two-level dose-response model was developed to describe the distributions of infectivity and pathogenicity in various challenge studies of adenovirus, incorporating differences in inoculation route as shift in average infectivity and pathogenicity. This dose-response model can be used to make predictions for the infectivity of adenovirus, specific to any of the four studied inoculation methods. The generalized adenovirus dose-response relationship for infection and acute illness takes into account variation in infectivity and/or pathogenicity across adenovirus types, as well as uncertainty due to limited data.

Adenoviruses
risk assessment
statistics
virus infection


Endovascular treatment of left internal thoracic artery aneurysm.

Abstract: Aneurysm of the internal thoracic artery is a rare entity, with variable presentation and a potential risk of fatal rupture. Angiotomography is the diagnostic test of choice and is useful for planning treatment. Considering the morbidity of thoracic access for a direct approach and the unpredictable risk of rupture, an endovascular procedure is the treatment modality of choice for this type of aneurysm. We describe the case of an internal thoracic artery aneurysm discovered incidentally during investigation of syncope and treated by embolization with low-profile and controlled-release microcoils.

endovascular procedures
aneurism
mammary arteries


Outcome of post-mastectomy radiotherapy after primary systemic treatment in patients with different clinical tumor and nodal stages of breast cancer: a cohort study.

Abstract: To evaluate the effect of post-mastectomy radiation therapy (PMRT) stratified by clinical tumor (T) or nodal (N) staging and determine predictors of overall survival (OS), locoregional recurrence (LRR), distant metastasis, and disease-free survival (DFS) in patients with breast cancer who received neoadjuvant chemotherapy (NACT) and total mastectomy (TM), we enrolled patients who received a diagnosis of breast invasive ductal carcinoma who received NACT followed by TM. Cox regression analysis was employed to calculate hazard ratios (HRs) and confidence intervals (CIs). Univariate and multivariate Cox regression analyses indicated that non-PMRT, Charlson comorbidity index ≥ 2, advanced clinical T or N stage, pathologic partial response, pathologic stationary disease, or pathologic progression disease were poor prognostic factors for OS. Well-differentiated tumor grade, pathologic complete response, and positive hormone receptors were better independent prognostic factors for OS. Adjusted HRs derived from PMRT for breast cancer after NACT and TM were 0.69 (0.53-0.89) and 0.74 (0.59-0.93) in clinical T3 and T4, respectively. aHRs derived from PMRT for breast cancer after NACT and TM were 0.67 (0.45-0.99), 0.75 (0.62-0.92), and 0.77 (0.60-0.98) in clinical N0, N1, N2-3, respectively. The aHRs (95% CI) of the PMRT group to the non-PMRT group for LRR-free survival and DFS were improved significantly. Our study indicated that PMRT significantly improved OS in clinical T3N0-T4N3 and for LRR-free survival and DFS in clinical T2N0-T4N3 from those of non-PMRT patients regardless of pathologic response and other predictors.

Zhang|Jia-Qiang|JQ| Lu|Chang-Yun|CY| Qin|Lei|L| Chen|Ho-Min|HM| Wu|Szu-Yuan|SY|

Breast cancer
post-mastectomy radiation therapy
overall survival
locoregional recurrence
metastasis


Exceptionally High, Strongly Temperature Dependent, Spin Hall Conductivity of SrRuO3.

Abstract: Spin-orbit torques (SOT) in thin film heterostructures originate from strong spin-orbit interactions (SOI) that, in the bulk, generate a spin current due either to extrinsic spin-dependent, skew, or/and side-jump scattering or to intrinsic Berry curvature in the conduction bands. While most SOT studies have focused on materials with heavy metal components, the oxide perovskite SrRuO3 has been predicted to have a pronounced Berry curvature. Through quantification of its spin current by the SOT exerted on an adjacent Co ferromagnetic layer, we determine that SrRuO3 has a strongly temperature ( T)-dependent spin Hall conductivity σ SH, increasing with the electrical conductivity, consistent with expected behavior of the intrinsic effect in the "dirty metal" regime. σ SH is very high at low T, e.g., σ SH > (ℏ/2 e)3 × 105 Ω-1 m-1 at 60 K, and is largely unaffected by the SrRuO3 ferromagnetic transition at T c ≈ 150 K, which agrees with a recent theoretical determination that the intrinsic spin Hall effect is magnetization independent. Below T c smaller nonstandard SOT components also develop associated with the magnetism of the oxide. Our results are consistent with the degree of RuO6 octahedral tilt being correlated with the strength of the SOI in this complex oxide, as predicted by recent theoretical work on strontium iridate. These results establish SrRuO3 as a very promising candidate material for implementing strong spintronics functionalities in oxide electronics.

Ou|Yongxi|Y|0000-0003-1008-7595
Wang|Zhe|Z|
Chang|Celesta S|CS|
Nair|Hari P|HP|
Paik|Hanjong|H|
Reynolds|Neal|N|
Ralph|Daniel C|DC|
Muller|David A|DA|
Schlom|Darrell G|DG|
Buhrman|Robert A|RA|

spin Hall conductivity
intrinsic spin Hall effect
complex oxide heterostructures
spin−orbit torques


Pulmonary Involvement during the Ebola Virus Disease.

Abstract: Filoviruses have become a worldwide public health concern, especially during the 2013-2016 Western Africa Ebola virus disease (EVD) outbreak-the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, including the liver, kidney, and lung. During the 2013-2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD. This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013-2016 Ebola outbreak.

Ebola virus
Ebola virus disease
lung pathogenesis
respiratory disease


A fuller picture of COVID-19 prognosis: the added value of vulnerability measures to predict mortality in hospitalised older adults.

Abstract:
BACKGROUND
Although coronavirus disease 2019 (COVID-19) disproportionally affects older adults, the use of conventional triage tools in acute care settings ignores the key aspects of vulnerability.

OBJECTIVE
This study aimed to determine the usefulness of adding a rapid vulnerability screening to an illness acuity tool to predict mortality in hospitalised COVID-19 patients.

DESIGN
Cohort study.

SETTING
Large university hospital dedicated to providing COVID-19 care.

PARTICIPANTS
Participants included are 1,428 consecutive inpatients aged ≥50 years.

METHODS
Vulnerability was assessed using the modified version of PRO-AGE score (0-7; higher = worse), a validated and easy-to-administer tool that rates physical impairment, recent hospitalisation, acute mental change, weight loss and fatigue. The baseline covariates included age, sex, Charlson comorbidity score and the National Early Warning Score (NEWS), a well-known illness acuity tool. Our outcome was time-to-death within 60 days of admission.

RESULTS
The patients had a median age of 66 years, and 58% were male. The incidence of 60-day mortality ranged from 22% to 69% across the quartiles of modified PRO-AGE. In adjusted analysis, compared with modified PRO-AGE scores 0-1 ('lowest quartile'), the hazard ratios (95% confidence interval) for 60-day mortality for modified PRO-AGE scores 2-3, 4 and 5-7 were 1.4 (1.1-1.9), 2.0 (1.5-2.7) and 2.8 (2.1-3.8), respectively. The modified PRO-AGE predicted different mortality risk levels within each stratum of NEWS and improved the discrimination of mortality prediction models.

CONCLUSIONS
Adding vulnerability to illness acuity improved accuracy of predicting mortality in hospitalised COVID-19 patients. Combining tools such as PRO-AGE and NEWS may help stratify the risk of mortality from COVID-19.

Aliberti|Márlon Juliano Romero|MJR|
Covinsky|Kenneth E|KE|
Garcez|Flavia Barreto|FB|
Smith|Alexander K|AK|
Curiati|Pedro Kallas|PK|
Lee|Sei J|SJ|
Dias|Murilo Bacchini|MB|
Melo|Victor José Dornelas|VJD|
Rego-Júnior|Otávio Fortes do|OFD|
Richinho|Valéria de Paula|VP|
Jacob-Filho|Wilson|W|
Avelino-Silva|Thiago J|TJ|

COVID-19
prognosis
mortality
triage
geriatric assessment
older people


BRAF/EZH2 Signaling Represses miR-129-5p Inhibition of SOX4 Thereby Modulating BRAFi Resistance in Melanoma.

Abstract: Many melanomas are associated with activating BRAF mutation. Targeted therapies by inhibitors of BRAF and MEK (BRAFi, MEKi) show marked antitumor response, but become limited by drug resistance. The mechanisms for this are not fully revealed, but include miRNA. Wishing to improve efficacy of BRAFi and knowing that certain miRNAs are linked to resistance to BRAFi, we wanted to focus on miRNAs exclusively associated with response to BRAFi. We found increased expression of miR-129-5p during BRAFi treatment of BRAF- mutant melanoma cells. Parallel to emergence of resistance we observed mir-129-5p expression to become suppressed by BRAF/EZH2 signaling. In functional analyses we revealed that miR-129-5p acts as a tumor suppressor as its overexpression decreased cell proliferation, improved treatment response and reduced viability of BRAFi resistant melanoma cells. By protein expression analyses and luciferase reporter assays we confirmed SOX4 as a direct target of mir-129-5p. Thus, modulation of the miR-129-5p-SOX4 axis could serve as a promising novel strategy to improve response to BRAFi in melanoma.

Gebhardt|Kathleen|K|
Edemir|Bayram|B|
Groß|Elisabeth|E|0000-0002-1506-9559
Nemetschke|Linda|L|
Kewitz-Hempel|Stefanie|S|
Moritz|Rose K C|RKC|
Sunderkötter|Cord|C|0000-0002-2929-145X
Gerloff|Dennis|D|

melanoma
BRAF mutation
miRNAs
therapy resistance


Borrelia afzelii alters reproductive success in a rodent host.

Abstract: The impact of a pathogen on the fitness and behaviour of its natural host depends upon the host-parasite relationship in a given set of environmental conditions. Here, we experimentally investigated the effects of Borrelia afzelii, one of the aetiological agents of Lyme disease in humans, on the fitness of its natural rodent host, the bank vole (Myodes glareolus), in semi-natural conditions with two contrasting host population densities. Our results show that B. afzelii can modify the reproductive success and spacing behaviour of its rodent host, whereas host survival was not affected. Infection impaired the breeding probability of large bank voles. Reproduction was hastened in infected females without alteration of the offspring size at birth. At low density, infected males produced fewer offspring, fertilized fewer females and had lower mobility than uninfected individuals. Meanwhile, the infection did not affect the proportion of offspring produced or the proportion of mating partner in female bank voles. Our study is the first to show that B. afzelii infection alters the reproductive success of the natural host. The effects observed could reflect the sickness behaviour due to the infection or they could be a consequence of a manipulation of the host behaviour by the bacteria.

Borrelia afzelii
fitness
natural host
Myodes glareolus
host–pathogen interaction
zoonosis


Downregulated SPINK4 is associated with poor survival in colorectal cancer.

Abstract:
BACKGROUND
SPINK4 is known as a gastrointestinal peptide in the gastrointestinal tract and is abundantly expressed in human goblet cells. The clinical significance of SPINK4 in colorectal cancer (CRC) is largely unknown.

METHODS
We retrieved the expression data of 1168 CRC patients from 3 Gene Expression Omnibus (GEO) datasets (GSE24551, GSE39582, GSE32323) and The Cancer Genome Atlas (TCGA) to compare the expression level of SPINK4 between CRC tissues and normal colorectal tissues and to evaluate its value in predicting the survival of CRC patients. At the protein level, these results were further confirmed by data mining in the Human Protein Atlas and by immunohistochemical staining of samples from 81 CRC cases in our own center.

RESULTS
SPINK4 expression was downregulated in CRC compared with that in normal tissues, and decreased SPINK4 expression at both the mRNA and protein levels was associated with poor prognosis in CRC patients from all 3 GEO datasets, the TCGA database and our cohort. Additionally, lower SPINK4 expression was significantly related to higher TNM stage. Moreover, in multivariate regression, SPINK4 was confirmed as an independent indicator of poor survival in CRC patients in all databases and in our own cohort.

CONCLUSIONS
We concluded that reduced expression of SPINK4 relates to poor survival in CRC, functioning as a novel indicator.

D015972:Gene Expression Regulation, Neoplastic

D000074162:Serine Peptidase Inhibitors, Kazal Type


Bacillus Calmette-Guerin 's beneficial impact on glucose metabolism: evidence for broad based applications.

Abstract: Bacillus Calmette-Guerin (BCG) vaccinations improve glycemic control in juvenile-onset Type I diabetes (T1D), an effect driven by restored sugar transport through aerobic glycolysis. In a pilot clinical trial, T1D, but not latent autoimmune diabetes of adults (LADA), exhibited lower blood sugars after multidose BCG. Using a glucose transport assay, monocytes from T1D subjects showed a large stimulation index with BCG exposures; LADA subjects showed minimal BCG-induced sugar responsiveness. Monocytes from T1D, type 2 diabetes (T2D), and non-diabetic controls (NDC) were all responsive in vitro to BCG by augmented sugar utilization. Adults with prior neonatal BCG vaccination show accelerated glucose transport decades later. Finally, in vivo experiments with the NOD mouse (a T1D model) and obese db/db mice (a T2D model) confirm BCG's blood-sugar-lowering and accelerated glucose metabolism with sufficient dosing. Our results suggest that BCG's benefits for glucose metabolism may be broadly applicable to T1D and T2D, but less to LADA.

Shpilsky|Gabriella F|GF|
Takahashi|Hiroyuki|H|
Aristarkhova|Anna|A|
Weil|Michele|M|
Ng|Nathan|N|
Nelson|Kacie J|KJ|
Lee|Amanda|A|
Zheng|Hui|H|
Kühtreiber|Willem M|WM|
Faustman|Denise L|DL|


Selected Organochlorines in Human Blood and Urine in the South of the Russian Far East.

Abstract: The trace OCP concentrations, such as α-, β-, and γ-HCH, DDT and its metabolites (DDD and DDE) in blood and urine of residents from the south of the Russian Far East was revealed. A large range of OCPs was found in the urine: α- and γ-isomers of HCH, DDT and DDE. The only β-HCH was detected in the blood; this indicates its persistence and the difficulty of excretion this substance from the organism. The total trace OCP concentration, found in the biological fluids of residents of the south of the Russian Far East, providing further evidence that these organic contaminants persist in the environment.

Tsygankov|Vasiliy Yu|VY|
Khristoforova|Nadezhda K|NK|
Lukyanova|Olga N|ON|
Boyarova|Margarita D|MD|
Kiku|Pavel F|PF|
Yarygina|Marina V|MV|


Effect of Type and Concentration of Nanoclay on the Mechanical and Physicochemical Properties of Bis-GMA/TTEGDMA Dental Resins.

Abstract: Bis-GMA/TTEGDMA-based resin composites were prepared with two different types of nanoclays: an organically modified laminar clay (Cloisite® 30B, montmorillonite, MMT) and a microfibrous clay (palygorskite, PLG). Their physicochemical and mechanical properties were then determined. Both MMT and PLG nanoclays were added into monomer mixture (1:1 ratio) at different loading levels (0, 2, 4, 6, 8 and 10 wt.%), and the resulting composites were characterized by scanning electron microscopy (SEM), thermogravimetric analysis (TGA), dynamic mechanical analysis (DMA) and mechanical testing (bending and compressive properties). Thermal properties, depth of cure and water absorption were not greatly affected by the type of nanoclay, while the mechanical properties of dental resin composites depended on both the variety and concentration of nanoclay. In this regard, composites containing MMT displayed higher mechanical strength (both flexural and compression) than those resins prepared with PLG due to a poor nanoclay dispersion as revealed by SEM. Solubility of the composites was dependent not only on nanoclay-type but also the mineral concentration. Dental composites fulfilled the minimum depth cure and solubility criteria set by the ISO 4049 standard. In contrast, the minimum bending strength (50 MPa) established by the international standard was only satisfied by the dental resins containing MMT. Based on these results, composites containing either MMT or PLG (at low filler contents) are potentially suitable for use in dental restorative resins, although those prepared with MMT displayed better results.

Encalada-Alayola|J J|JJ|
Veranes-Pantoja|Y|Y|
Uribe-Calderón|J A|JA|
Cauich-Rodríguez|J V|JV|
Cervantes-Uc|J M|JM|

montmorillonite
palygorskite
dental resin composite


Early onset of efficacy with erenumab in patients with episodic and chronic migraine.

Abstract:
BACKGROUND
Subcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a ≥ 50% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM). Early efficacy of migraine preventive medications is an important treatment characteristic to patients. Delays in achievement of efficacy can result in failed adherence. The objective of these post-hoc analyses were to evaluate efficacy in the first 4 weeks after initial subcutaneous administration of erenumab 70 mg, erenumab 140 mg, or placebo.

METHODS
There is no generally accepted methodology to measure onset of action for migraine preventive medications. We used a comprehensive approach with data from both studies to evaluate change from baseline in weekly migraine days (WMD), achievement of ≥ 50% reduction in WMD, and proportion of patients experiencing migraine measured on a daily basis. The 7-day moving averages were overlaid with observed data.

RESULTS
In both studies (EM: N = 955; CM: N = 667), there was evidence of onset of efficacy of erenumab vs. placebo during the first week of treatment, which in some cases reached nominal significance. For EM the changes in WMD were (least squares mean [LSM] [95% CI]): placebo, - 0.1 (- 0.3, 0.0); erenumab 70 mg, - 0.3 (- 0.5, - 0.2) p = 0.130; erenumab 140 mg, - 0.6 (- 0.7, - 0.4) p < 0.001. For CM the changes were: placebo, - 0.5 (- 0.8, - 0.3); erenumab 70 mg, - 0.9 (- 1.2, - 0.7) p = 0.047; erenumab 140 mg, - 0.8 (- 1.1, - 0.5) p = 0.18. Achievement of ≥ 50% reduction in WMD was observed as early as Week 1 (adjusted OR [95% CI] erenumab vs placebo) in EM: erenumab 70 mg, 1.3 (1.0, 1.9) p = 0.097; erenumab 140 mg, 2.0 (1.4, 2.7) p < 0.001. A similar outcome was observed for CM: erenumab 70 mg, 1.8 (1.1, 2.8) p = 0.011; erenumab 140 mg, 1.9 (1.2, 2.9) p = 0.009. Seven-day moving averages of observed data showed each treatment arm differed from placebo by Week 1 (OR [95% CI]): in EM Day 3 for erenumab 140 mg, 0.7 (0.5, 1.0) p = 0.031 and at Day 7 for 70 mg, 0.6 (0.4, 0.8) p = 0.002; in CM: Day 6 for erenumab 70 mg, 0.6 (0.4, 0.9) p = 0.022 and at Day 7 for 140 mg, 0.7 (0.4, 1.0); p = 0.038.

CONCLUSION
Erenumab showed early onset of efficacy with separation from placebo within the first week of treatment in both chronic and episodic migraine patients.

Onset of efficacy
Efficacy
Erenumab
Chronic migraine
Episodic migraine
Migraine preventive medication
Migraine preventive clinical trial


Anatomic and neuromuscular characterisation of the equine cricothyroid muscle.

Abstract:
REASONS FOR PERFORMING STUDY
As part of investigation into laryngeal stability and reanimation using functional electrical stimulation, the cricothyroid muscle might be utilised to increase laryngeal cross-sectional area in horses with recurrent laryngeal neuropathy. For optimal electrode placement and muscle recruitment, the neuroanatomy and excitability of the equine cricothyroid muscle needs to be defined.

OBJECTIVES
To describe the anatomy, innervation and function of the equine cricothyroid muscle and its contribution to laryngeal diameter.

METHODS
Seventeen equine larynges were collected at necropsy and 12 were grossly dissected. Seven larynges (five grade 1, two grade 4) were prepared for immunohistochemistry following gross dissection and 5 larynges were prepared for special staining: acetylcholinesterase staining of motor endplates (n = 3) and Sihler's staining (n = 2). Three larynges were stimulated following in situ cadaver dissection and 2 larynges were removed and stimulated ex vivo.

RESULTS
Three neuromuscular compartments, each innervated by a primary nerve branch of the external branch of the cranial laryngeal nerve, were identified in all larynges. Stimulation of each neuromuscular compartment resulted in ventral displacement of the thyroid cartilage with respect to the cricoid cartilage, thereby increasing dorsoventral height of the rima glottis.

CONCLUSIONS
The equine cricothyroid muscle has 3 distinct neuromuscular compartments with discrete innervation, fibre type distribution and muscle fibre sizes. All neuromuscular compartments tense the vocal cords by increasing dorsoventral height of the rima glottis through ventral displacement of the thyroid cartilage with respect to the cricoid cartilage.

POTENTIAL RELEVANCE
Simultaneous functional electrical stimulation of the cricothyroid and dorsal cricoarytenoid muscles may enhance laryngeal cross-sectional area in horses with recurrent laryngeal neuropathy.

Reesink|H L|HL|
Hermanson|J W|JW|
Cheetham|J|J|
Mu|L|L|
Mitchell|L M|LM|
Soderholm|L V|LV|
Ducharme|N G|NG|

cricothyroid muscle horse anatomy larynx


Optimization of hydrogen and syngas production from PKS gasification by using coal bottom ash.

Abstract: Catalytic steam gasification of palm kernel shell is investigated to optimize operating parameters for hydrogen and syngas production using TGA-MS setup. RSM is used for experimental design and evaluating the effect of temperature, particle size, CaO/biomass ratio, and coal bottom ash wt% on hydrogen and syngas. Hydrogen production appears highly sensitive to all factors, especially temperature and coal bottom ash wt%. In case of syngas, the order of parametric influence is: CaO/biomass>coal bottom ash wt%>temperature>particle size. The significant catalytic effect of coal bottom ash is due to the presence of Fe2O3, MgO, Al2O3, and CaO. A temperature of 692°C, coal bottom ash wt% of 0.07, CaO/biomass of 1.42, and particle size of 0.75mm are the optimum conditions for augmented yield of hydrogen and syngas. The production of hydrogen and syngas is 1.5% higher in the pilot scale gasifier as compared to TGA-MS setup.

Shahbaz|Muhammad|M|
Yusup|Suzana|S|
Inayat|Abrar|A|
Patrick|David Onoja|DO|
Pratama|Angga|A|
Ammar|Muhamamd|M|

Hydrogen
Syngas
Gasification
Coal bottom ash
RSM
Biomass


Surveillance Colonoscopy after Appendicectomy in Patients over the Age of 40: Targeted Audit of Outcomes and Variability in Practice.

Abstract: Introduction: Recent evidence suggests the need to proceed with a surveillance colonoscopy in patients above the age of 40 years who undergo appendicectomy for acute appendicitis, given the higher risk of an underlying colonic tumor. After anecdotally observing a substantial variability in terms of adaptation of these recommendations by the on-call surgical teams, we performed a clinical audit regarding our relevant endoscopic follow-up compliance rates to identify areas for improvement of our practise. Materials Methods: We performed a retrospective review of the electronic records of all patients above 40 years who had appendicectomy for acute appendicitis within a 3-year period in our institution, assessing as primary outcome the actual performance of a follow-up colonoscopy and the detected endoscopic findings. Results: Our results demonstrated that more than 80% of our patients did not have an endoscopic follow-up, as suggested by the current evidence. In addition, with respect to the subspecialisation of the parent surgical team, it seems that non-colorectal teams had lower compliance regarding the arrangement of endoscopic surveillance, when compared to specialist colorectal team. Conclusions: Emergency surgical teams need to be further educated with respect to the current practise recommendations concerning the appropriate endoscopic follow-up after the performance of appendicectomy for acute appendicitis. Establishment of dedicated bundles of postoperative care, as well as clear relevant guidance from the gastrointestinal/emergency surgery societies would be of great value in this direction.

Seretis|Charalampos|C| Gill|Jagjit|J| Lim|Paul|P| Archer|Lucy|L| Seretis|Fotios|F| Yahia|Shuker|S|


Lead, mercury, and selenium alter physiological functions in wild caimans (Caiman crocodilus).

Abstract: Environmental contaminants affect ecosystems worldwide and have deleterious effects on biota. Non-essential mercury (Hg) and lead (Pb) concentrations are well documented in some taxa and are described to cause multiple detrimental effects on human and wildlife. Additionally, essential selenium (Se) is known to be toxic at high concentrations but, at lower concentrations, Se can protect organisms against Hg toxicity. Crocodilians are known to bioaccumulate contaminants. However, the effects of these contaminants on physiological processes remain poorly studied. In the present study, we quantified Hg, Pb and Se concentrations in spectacled caimans (Caiman crocodilus) and investigated the effects of these contaminants on several physiological processes linked to osmoregulatory, hepatic, endocrine and renal functions measured through blood parameters in 23 individuals. Mercury was related to disruption of osmoregulation (sodium levels), hepatic function (alkaline phosphatase levels) and endocrine processes (corticosterone levels). Lead was related to disruption of hepatic functions (glucose and alanine aminotransferase levels). Selenium was not related to any parameters, but the Se:Hg molar ratio was positively related to the Na+ and corticosterone concentrations, suggesting a potential protective effect against Hg toxicity. Overall, our results suggest that Hg and Pb alter physiological mechanisms in wild caimans and highlight the need to thoroughly investigate the consequences of trace element contamination in crocodilians.

Lemaire|Jérémy|J| Bustamante|Paco|P| Mangione|Rosanna|R| Marquis|Olivier|O| Churlaud|Carine|C| Brault-Favrou|Maud|M| Parenteau|Charline|C| Brischoux|François|F|

Crocodilians
Osmoregulation
Corticosterone
Trace elements
Blood chemistry


Carbon monoxide attenuates LPS-induced myocardial dysfunction in rats by regulating the mitochondrial dynamic equilibrium.

Abstract: Lipopolysaccharide (LPS) induces myocardial dysfunction by damaging the mitochondrial structure in cardiomyocytes. Since low levels of carbon monoxide can confer cytoprotective effects against end-organ damage from endotoxic shock, we tested whether treatment with carbon monoxide-releasing molecule-2 (CORM-2) could ameliorate LPS-induced myocardial dysfunction in rats by maintaining the dynamic equilibrium between the mitochondrial fusion and fission processes. Cardiac function, myocardial histopathology, myocardial enzymes, and changes in myocardial mitochondrial function and mitochondrial fusion-fission protein expression were assessed in rats. The mitochondrial structure and morphology were studied by electron microscopy, and the expression levels of key proteins involved in the mitochondrial dynamics were assessed by Western blot assay. Cardiac dysfunction and increased myocardial enzyme activity together with myocardial pathological damage, mitochondrial dysfunction, and impaired mitochondrial dynamics homeostasis were observed in the LPS-challenged septic rats. However, these observations were reversed by CORM-2, which effectively inhibited cardiac and mitochondrial damage in the LPS-challenged rats and improved the survival rate of the animals. In conclusion, CORM-2 regulates the LPS-induced imbalance of the dynamic mitochondrial fusion and fission processes, thereby effectively ameliorating the LPS-induced myocardial dysfunction and improving the survival of the rats.

Zhang|Sheng|S| Xu|Yanping|Y| Zhu|Jinyuan|J| Ma|Jinlan|J| Niu|Qingsheng|Q| Wang|Xiaohong|X|

Carbon monoxide
Myocardial dysfunction
Lipopolysaccharide
Mitochondrial fusion and fission


Mitochondrial DNA analysis of ancient sheep from Altai.

Abstract: A comparative analysis of the genetic diversity of ancient and modern sheep can shed light on the origin of these animals and their distribution as well as help to evaluate the role of humans at each formation stage of different sheep breeds. Here we isolated ancient DNA and performed sequencing of the mitochondrial DNA D-loop from 17 sheep bone remains (~4000-1000 years old) found in the archaeological complexes in the south of Altai (Western Siberia). The length of the sequences obtained ranged between 318 and 586 bp. The haplotype diversity and nucleotide diversity were 0.801 ± 0.081 and 0.0096 ± 0.0014 respectively. The average number of nucleotide differences was ~3.1. Nucleotide sequence analysis revealed that 15 specimens were nested within previously described A,B,C,D and E lineages and that two specimens had a basal position relative to the rest of the analyzed samples. A relatively high diversity of sheep haplotypes, including the presence of two basal haplotypes, indicates that the Altai region may have been a transport route of human migration. Further ancient DNA analysis of other specimens and deeper genome sequencing of samples with novel haplotypes is needed to better understand the demographic history of sheep in Southern Siberia.

sequencing
Western Siberia
haplotyping
lineage
Ovis aries
aDNA
archaeological remains
domestication


Self-Heating Graphene Nanocomposite Bricks: A Case Study in China.

Abstract: In cold climate regions, the energy associated with indoor heating constitutes a large portion of energy consumption. Increasing energy utilization efficiency is critically important for both economic and environmental reasons. Directly converting electrical energy to thermal energy using joule heating construction elements can save energy and investment to the water pipelines which have been extensively used for indoor heating in China. The fired brick has been extensively used to make pavements, walls and other masonry. Taking advantage of the high dispersion quality of graphene oxide (GO) in water, as well as the firing process used to make fired bricks, graphene nanocomposite bricks with excellent electrical properties and improved mechanical performance were prepared in China. The compressive strength of the bricks showed a substantial increase from 3.15 MPa to 7.21 MPa when GO concentration was 0.1 wt.%. Through applying 5 volts of electrical field within 5 minutes, the nanocomposites can be heated from room temperature to 60 °C, 110 °C and 160 °C for the nanocomposite bricks with graphene concentration of 3 wt.%, 4 wt.% and 5 wt.%, respectively, due to the extremely low percolation threshold (~0.5 wt.%) and high conductivity (10 Ω·cm at 1 wt.%). The sheets were connected more tightly when the GO content was increased. The thermal efficiency can reach up to 88% based on the applied voltage, measured resistance and temperature rise curves.

Tang|Zhuo|Z| Lu|Dong|D| Gong|Jing|J| Shi|Xianming|X|0000-0003-3576-8952 Zhong|Jing|J|

self-heating
nanocomposite bricks
energy consumption
graphene oxide


Primary Yolk Sac Tumor in the Cerebellar Hemisphere: A Case Report and Literature Review of the Rare Tumor.

Abstract: Yolk sac tumor (YST) is one of rare malignant germ cell tumors (GCTs). Primary intracranial YST, also endodermal sinus tumor (EST), is a quite rare type of brain tumor. Here, we report a case of YST, review the relevant literature, and propose a treatment strategy for this rare tumor. A 6-year-old boy initially manifested symptoms of dizziness and vomiting. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a large irregular oval tumor in the cerebellar hemisphere. We subtotally removed the tumor by microsurgery through the left suboccipital approach. Immunohistochemical staining showed that alpha fetoprotein (AFP) was positive and the Ki-67 proliferation index was high (60%), suggesting a germ cell tumor. After 3 months of follow-up, neither recurrence of tumor nor complications were found in the patient. The diagnosis of YST should be confirmed on the basis of clinical manifestations, neuroimaging and pathological findings. Gross total resection (GTR) is an ideal treatment for YST. However, due to the location of the tumor, GTR is usually difficult, and the rate of postoperative complications is high. This reported case shows that subtotal resection can be a good treatment strategy for YST.

Wu|Na|N| Chen|Qiang|Q| Chen|Meng|M| Ning|Jinbo|J| Peng|Shulei|S| Zhang|Taotao|T| Zhong|Wen|W| Duan|Song|S| Cheng|Chongjie|C| Xie|Yimin|Y|

yolk sac tumor
cerebellar hemisphere
endodermal sinus tumor
microsurgery
subtotal resection


Higher catalytic activity of porphyrin functionalized Co₃O ₄ nanostructures for visual and colorimetric detection of H₂ O₂ and glucose.

Abstract: 5,10,15,20-Tetrakis(4-carboxyl pheyl)-porphyrin (H2TCPP) functionalized chain-like Co3O4 nanoparticles (NPs) were prepared by a facile two-step method. The H2TCPP-Co3O4 nanocomposites were demonstrated to display enhanced peroxidase-like activity than that of pure Co3O4 nanoparticles without modification with H2TCPP molecules, catalyzing oxidation of peroxidase substrate 3,3',5,5'-tetramethyl-benzidine (TMB) in the presence of H2O2 to produce a blue color reaction. Furthermore, H2TCPP-Co3O4 nanocomposites showed typical Michaelis-Menten kinetics and higher affinity to H2O2 and TMB than that of pure Co3O4 NPs alone. Based on H2TCPP-Co3O4 nanocomposites, a simple, sensitive and selective colorimetric method with TMB as the substrate for the detection of H2O2 and glucose was successfully established. This colorimetric method can be used for the colorimetric detection of H2O2 with a low detection limit of 4×10(-7)mol·L(-1) and a dynamic range of 1×10(-6)mol·L(-1) to 75×10(-6)mol·L(-1). This method was designed to detect glucose when combined with glucose oxidase at a low detection limit of 8.6×10(-7)mol·L(-1) and a dynamic range of 1×10(-6)mol·L(-1) to 10×10(-6)mol·L(-1). Results of a fluorescent probe suggested that the peroxidase-mimic activity of the H2TCPP-Co3O4 nanocomposites effectively catalyzed the decomposition of H2O2 into [OH] radicals.

Liu|Qingyun|Q| Zhu|Renren|R| Du|Hui|H| Li|Hui|H| Yang|Yanting|Y| Jia|Qingyan|Q| Bian|Bing|B|


Fluorescence Sensing Behavior for the Detection of Alcoholic Strength and Water Based on Two Novel Metallic Complex Edifices.

Abstract: Alcoholic strength is a fundamental variable in industry production and its determination is crucial in technological developments. This study offers a novel strategy for fluorescent sensing of alcoholic content based on a terbium coordination complex. In pure water, the emissive compound displays blue luminescence. However, the addition of ethanol into the aqueous solution has induced the recovery of terbium green emissions. In another case, the achieved Eu(III)-phenanthroline complex shows high sensitivity to solvent polarity and the detection of trace amount of water can be realized through an "on-off" change with a low detection limit of 32.4 ppm.

Luminescence Lanthanide Responsive Sensors


Goblet cell LRRC26 regulates BK channel activation and protects against colitis in mice.

Abstract: Goblet cells (GCs) are specialized cells of the intestinal epithelium contributing critically to mucosal homeostasis. One of the functions of GCs is to produce and secrete MUC2, the mucin that forms the scaffold of the intestinal mucus layer coating the epithelium and separates the luminal pathogens and commensal microbiota from the host tissues. Although a variety of ion channels and transporters are thought to impact on MUC2 secretion, the specific cellular mechanisms that regulate GC function remain incompletely understood. Previously, we demonstrated that leucine-rich repeat-containing protein 26 (LRRC26), a known regulatory subunit of the Ca2+-and voltage-activated K+ channel (BK channel), localizes specifically to secretory cells within the intestinal tract. Here, utilizing a mouse model in which MUC2 is fluorescently tagged, thereby allowing visualization of single GCs in intact colonic crypts, we show that murine colonic GCs have functional LRRC26-associated BK channels. In the absence of LRRC26, BK channels are present in GCs, but are not activated at physiological conditions. In contrast, all tested MUC2- cells completely lacked BK channels. Moreover, LRRC26-associated BK channels underlie the BK channel contribution to the resting transepithelial current across mouse distal colonic mucosa. Genetic ablation of either LRRC26 or BK pore-forming α-subunit in mice results in a dramatically enhanced susceptibility to colitis induced by dextran sodium sulfate. These results demonstrate that normal potassium flux through LRRC26-associated BK channels in GCs has protective effects against colitis in mice.

D051036:Large-Conductance Calcium-Activated Potassium Channels

LRRC26
Ca2+-activated K+ channels
DSS-induced colitis
epithelial cells
inflammatory bowel disease


Association of preoperative medication with postoperative length of stay in elderly patients undergoing hip fracture surgery.

Abstract:
BACKGROUND
For elderly patients who are about to undergo surgery, research on the effects of preoperative medication on postoperative outcomes is rare, especially preoperative discontinuation-requiring medication (PDRM) which needed to be discontinued because of its increased risk of postoperative complications.

AIM
To investigate whether preoperative medication (PDRM and polypharmacy) is associated with postoperative length of hospital stay (LOS) in elderly patients undergoing hip fracture surgery.

METHODS
Patients aged ≥ 65 who were scheduled for hip (limited to femoral tuberosity) fracture surgery were included. Baseline characteristics, preoperative medication and postoperative LOS were collected from the electronic medical record. The primary outcome was postoperative LOS.

RESULTS
A total of 369 hip fracture patients were included. There were 188 and 122 patients exposed to PDRM and polypharmacy, respectively. Multivariate analysis models were constructed using significant factors for prolonged postoperative hospital stay from univariate analysis: Model I (body mass index (BMI), Charlson comorbidity index (CCI) ≥ 7, creatinine clearance rate (Ccr) < 60 and PDRM) and Model II (BMI, Ccr ≥ 7, Ccr < 60 and polypharmacy). CCI was the most significant factor. Its adjusted odds ratio was as large as 2.7 and attributable risk was 63%. In preoperative medication use, both polypharmacy and PDRM showed significant association with postoperative LOS.

CONCLUSION
The present study supported the impact of PDRM on postoperative LOS in geriatric hip fracture patients. The results added a further aspect to preoperative medication optimization in elderly patients undergoing hip fracture surgery.

D000368:Aged
D006620:Hip Fractures
D006801:Humans
D007902:Length of Stay
D016017:Odds Ratio
D011183:Postoperative Complications
D012189:Retrospective Studies
D012307:Risk Factors


Lineage-specific adaptation to climate involves flowering time in North American Arabidopsis lyrata.

Abstract: Adaptation to local climatic conditions is commonly found within species, but whether it involves the same intraspecific genomic variants is unknown. We studied this question in North American Arabidopsis lyrata, whose current distribution is shaped by post-glacial range expansion from two refugia, resulting in two distinct genetic clusters covering comparable climatic gradients. Using pooled whole-genome sequence data of 41 outcrossing populations, we identified loci associated with three niche-determining climatic variables in the two clusters and compared these outliers. Little evidence was found for parallelism in climate adaptation for single nucleotide polymorphisms (SNPs) and for genes with an accumulation of outlier SNPs. Significantly increased selection coefficients supported them as candidates of climate adaptation. However, the fraction of gene ontology (GO) terms shared between clusters was higher compared to outlier SNPs and outlier genes, suggesting that selection acts on similar pathways but not necessarily the same genes. Enriched GO terms involved responses to abiotic and biotic stress, circadian rhythm and development, with flower development and reproduction being among the most frequently detected. In line with GO enrichment, regulators of flowering time were detected as outlier genes. Our results suggest that while adaptation to environmental gradients on the genomic level are lineage-specific in A. lyrata, similar biological processes seem to be involved. Differential loss of standing genetic variation, probably driven by genetic drift, can in part account for the lack of parallel evolution on the genomic level.

Arabidopsis lyrata
range expansion
climate adaptation
environmental gradient
parallel evolution
genome-wide association study GWAS
reproductive phenology


Molecular integration of HoxB4 and STAT3 for self-renewal of hematopoietic stem cells: a model of molecular convergence for stemness.

Abstract: The upregulation of HoxB4 promotes self-renewal of hematopoietic stem cells (HSCs) without overriding the normal stem cell pool size. A similar enhancement of HSC self-renewal occurs when signal transducer and activator of transcription 3 (STAT3) is activated in HSCs. In this study, to gain insight into the functional organization of individual transcription factors (TFs) that have similar effects on HSCs, we investigated the molecular interplay between HoxB4 and STAT3 in the regulation of HSC self-renewal. We found that while STAT3-C or HoxB4 similarly enhanced the in vitro self-renewal and in vivo repopulating activities of HSCs, simultaneous transduction of both TFs did not have additive effects, indicating their functional redundancy in HSCs. In addition, activation of STAT3 did not cause changes in the expression levels of HoxB4. In contrast, the inhibition of STAT3 activity in HoxB4-overexpressing hematopoietic cells significantly abrogated the enhancing effects of HoxB4, and the upregulation of HoxB4 caused a ligand-independent Tyr-phosphorylation of STAT3. Microarray analysis revealed a significant overlap of the transcriptomes regulated by STAT3 and HoxB4 in undifferentiated hematopoietic cells. Moreover, a gene set enrichment analysis showed significant overlap in the candidate TFs that can recapitulate the transcriptional changes induced by HoxB4 or STAT3. Interestingly, among these common TFs were the pluripotency-related genes Oct-4 and Nanog. These results indicate that tissue-specific TFs regulating HSC self-renewal are functionally organized to play an equivalent role in transcription and provide insights into the functional convergence of multiple entries of TFs toward a conserved transcription program for the stem cell state.

Hong|Sung-Hyun|SH|
Yang|Seung-Jip|SJ|
Kim|Tae-Min|TM|
Shim|Jae-Seung|JS|
Lee|Ho-Sun|HS|
Lee|Ga-Young|GY|
Park|Bo-Bae|BB|
Nam|Suk Woo|SW|
Ryoo|Zae Young|ZY|
Oh|Il-Hoan|IH|

D020411:Oligonucleotide Array Sequence Analysis

D020133:Reverse Transcriptase Polymerase Chain Reaction

HoxB4
Self-renewal
Hematopoietic stem cell


ELF: A new measure of response capture.

Abstract: Response capture is a widespread and extensively studied phenomenon, in particular in decision tasks involving response conflict. Its intensity is routinely quantified by conditional accuracy function (CAF). We argue that this method might be misleading, and propose an alternative approach, the error location function (ELF). While CAF provides the error rate by bins of reaction time (RT), ELF represents the share of total errors below each quantile of RT. We derive from ELF an index of response capture, the error location index (ELI), which represents the area below the ELF. Using simulations of computational models, we show that ELF and ELI specifically quantify variations in response capture. Finally, we illustrate the usefulness of ELF and ELI through experimental data and show that ELF and CAF can yield to contradictory conclusions.

Computational models
Cognitive control and automaticity
Reaction time analysis
Response time models


Anti-Inflammatory Effects of Dimethyl Fumarate in Microglia via an Autophagy Dependent Pathway.

Abstract: Dimethyl fumarate (DMF), which has been approved by the Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis, is considered to exert anti-inflammatory and antioxidant effects. Microglia maintain homeostasis in the central nervous system and play a key role in neuroinflammation, while autophagy controls numerous fundamental biological processes, including pathogen removal, cytokine production, and clearance of toxic aggregates. However, the role of DMF in autophagy induction and the relationship of this effect with its anti-inflammatory functions in microglia are not well known. In the present study, we investigated whether DMF inhibited neuroinflammation and induced autophagy in microglia. First, we confirmed the anti-neuroinflammatory effect of DMF in mice with streptozotocin-induced diabetic neuropathy. Next, we used in vitro models including microglial cell lines and primary microglial cells to examine the anti-inflammatory and neuroprotective effects of DMF. We found that DMF significantly inhibited nitric oxide and proinflammatory cytokine production in lipopolysaccharide-stimulated microglia and induced the switch of microglia to the M2 state. In addition, DMF treatment increased the expression levels of autophagy markers including microtubule-associated protein light chain 3 (LC3) and autophagy-related protein 7 (ATG7) and the formation of LC3 puncta in microglia. The anti-inflammatory effect of DMF in microglia was significantly reduced by pretreatment with autophagy inhibitors. These data suggest that DMF leads to the induction of autophagy in microglia and that its anti-inflammatory effects are partially mediated through an autophagy-dependent pathway.

Lee|Young-Sun|YS|
Gupta|Deepak Prasad|DP|
Park|Sung Hee|SH|
Yang|Hyun-Jeong|HJ|
Song|Gyun Jee|GJ|

microglia autophagy DMF neuroinflammation anti-inflammation


Utility gains from reductions in the modifiable burden of lung cancer attributable to residential radon in Canada.

Abstract:
RESEARCH QUESTION
The objective of this analysis is to estimate the modifiable burden of disease according to the annual number of lung cancer deaths prevented and the associated period gain in quality-adjusted life years (QALYs) for the 2012 populations in Canada from reductions in residential radon exposures.

INTERVENTIONS
Two postulated interventions for residential radon mitigation in new construction are assessed, corresponding to a 50% reduction and an 85% reduction in radon nationally, in the provinces/territories, and in 17 census metropolitan areas in Canada.

METHODS
Data were derived from two recent Canadian radon surveys conducted by the Radiation Protection Bureau, Health Canada, along with Canadian mortality and quality of life data. Analyses adopted a lifetime horizon and a discount rate of 1.5%. A period life-table analysis was conducted using age- and sex-specific all-cause and lung cancer mortality rates, adjusted for smoking, and the BEIR VI exposure-age-concentration model for radon-attributable risk of lung cancer mortality.

RESULTS
A reduction in residential radon by 50% could prevent 681 lung cancer deaths, associated with a gain of 15,445 QALYs in the Canadian population at a discount rate of 1.5%; a reduction in radon by 85% could prevent 1263 lung cancer deaths, associated with a gain of 26,336 QALYs. On a per population basis, the Yukon was estimated to benefit most from radon mitigation.

CONCLUSION
The magnitude of QALY gains in Canada estimated under the two radon mitigation scenarios is appreciable but varies considerably across provinces due to variability in indoor radon concentrations and smoking rates.

Gaskin|Janet|J|0000-0001-5326-4921 Coyle|Doug|D| Whyte|Jeff|J| Krewski|Dan|D|

Lung cancer
Radon
Quality-adjusted life years
Exposure mitigation
Life tables


Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies.

Abstract: In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3.3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52.6 (range 21-74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases.

Wiberg|A|A| Granstam|A|A| Ingvast|S|S| Härkönen|T|T| Knip|M|M| Korsgren|O|O| Skog|O|O|

D016381:Islets of Langerhans Transplantation

D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8

autoantibodies
type 1 diabetes
fibrosis
exocrine pancreas
inflammation