Health and Wellbeing in an Outdoor and Adventure Sports Context.

Abstract: Outdoor and adventure sports (OAS) have been linked to positive health and wellbeing outcomes. This Special Edition brings together cutting-edge research and thought on the implications of this link. An analysis of the papers in this Special Edition reveals important insights into (i) the diverse and powerful outcomes derived from adventure experiences, (ii) how adventure experiences facilitate these outcomes, (iii) how best to design outdoor and adventure experiences. The evidence in this edition indicates a need for a more systematic approach to the inclusion of OAS as important to good health and wellbeing. OAS should be included as part of education, health, policy and planning.

Allan|John|J|0000-0001-5314-5076 Hardwell|Ashley|A| Kay|Chris|C| Peacock|Suzanne|S| Hart|Melissa|M| Dillon|Michelle|M| Brymer|Eric|E|0000-0003-0274-1016


Energy Drinks Induce Acute Cardiovascular and Metabolic Changes Pointing to Potential Risks for Young Adults: A Randomized Controlled Trial.

Abstract:
BACKGROUND
Case reports suggest a link between energy drinks (EDs) and adverse events, including deaths.

OBJECTIVES
We examined cardiovascular and metabolic effects of EDs and mixtures providing relevant ingredients of EDs compared to a similarly composed control product (CP) without these components.

METHODS
This randomized, crossover trial comprised 38 adults (19 women, mean BMI 23 kg/m2, mean age 22 y). We examined effects of a single administration of a commercial ED, the CP, and the CP supplemented with major ED-ingredients at the same concentrations as in the ED. The study products were administered at 2 volumes, 750 or 1000 mL.

RESULTS
Both volumes of the study products were acceptably tolerated with no dose-dependent effects on blood pressure (BP, primary outcome), heart rate, heart rate corrected duration of QT-segment in electrocardiography (QTc interval), and glucose metabolism. After ED consumption, 11% of the participants reported symptoms, in contrast to 0-3% caused by other study products. After 1 h, administration of an ED caused an increase in systolic BP (116.9 ± 10.4 to 120.7 ± 10.7 mmHg, mean ± SD, P < 0.01) and a QTc prolongation (393.3 ± 20.6 to 400.8 ± 24.1 ms, P < 0.01). Also caffeine, but not taurine or glucuronolactone, caused an increase in BP, but no QTc prolongation. The BP effects were most pronounced after 1 h and returned to normal after a few hours. All study products caused a decrease in serum glucose and an increase in insulin concentrations after 1 h compared to baseline values, corresponding to an elevation in the HOMA-IR (ED + 4.0, other products + 1.0-2.8, all P < 0.001).

CONCLUSION
A single high-volume intake of ED caused adverse changes in BP, QTc, and insulin sensitivity in young, healthy individuals. These effects of EDs cannot be easily attributed to the single components caffeine, taurine, or glucuronolactone. This trial was registered at clinicaltrials.gov as NCT01421979.

Basrai|Maryam|M|
Schweinlin|Anna|A|
Menzel|Juliane|J|
Mielke|Hans|H|
Weikert|Cornelia|C|
Dusemund|Birgit|B|
Putze|Kersten|K|
Watzl|Bernhard|B|
Lampen|Alfonso|A|
Bischoff|Stephan C|SC|

energy drinks
young adults
QTc interval
caffeine
taurine
glucuronolactone
cardiovascular risk
glucose tolerance
hypertension


Arginase Is Essential for Survival of Leishmania donovani Promastigotes but Not Intracellular Amastigotes.

Abstract: Studies of Leishmania donovani have shown that both ornithine decarboxylase and spermidine synthase, two enzymes of the polyamine biosynthetic pathway, are critical for promastigote proliferation and required for maximum infection in mice. However, the importance of arginase (ARG), the first enzyme of the polyamine pathway in Leishmania, has not been analyzed in L. donovani To test ARG function in intact parasites, we generated Δarg null mutants in L. donovani and evaluated their ability to proliferate in vitro and trigger infections in mice. The Δarg knockout was incapable of growth in the absence of polyamine supplementation, but the auxotrophic phenotype could be bypassed by addition of either millimolar concentrations of ornithine or micromolar concentrations of putrescine or by complementation with either glycosomal or cytosolic versions of ARG. Spermidine supplementation of the medium did not circumvent the polyamine auxotrophy of the Δarg line. Although ARG was found to be essential for ornithine and polyamine synthesis, ornithine decarboxylase appeared to be the rate-limiting enzyme for polyamine production. Mouse infectivity studies revealed that the Δarg lesion reduced parasite burdens in livers by an order of magnitude but had little impact on the numbers of parasites recovered from spleens. Thus, ARG is essential for proliferation of promastigotes but not intracellular amastigotes. Coupled with previous studies, these data support a model in which L. donovani amastigotes readily salvage ornithine and have some access to host spermidine pools, while host putrescine appears to be unavailable for salvage by the parasite.

Boitz|Jan M|JM|
Gilroy|Caslin A|CA|
Olenyik|Tamara D|TD|
Paradis|Dustin|D|
Perdeh|Jasmine|J|
Dearman|Kristie|K|
Davis|Madison J|MJ|
Yates|Phillip A|PA|
Li|Yuexin|Y|
Riscoe|Michael K|MK|
Ullman|Buddy|B|
Roberts|Sigrid C|SC|


In Vitro and In Vivo Modeling of Spinal and Bulbar Muscular Atrophy.

Abstract: Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease characterized by late-onset, progressive degeneration of lower motor neurons and skeletal muscle atrophy. SBMA is caused by expansions of a CAG trinucleotide repeat in the gene encoding the androgen receptor (AR). One striking feature of SBMA is sex specificity: SBMA fully manifests only in males, whereas females show subclinical or mild disease manifestations even when homozygous for the mutation. Since the identification of the mutation responsible for SBMA in 1991, several cell and animal models have been developed to recapitulate the main features of disease in vitro and in vivo. In this review, we describe the most widely used cellular and animal models of SBMA, highlighting advantages and disadvantages in the use of these models to gain mechanistic and therapeutic insights into SBMA.

Spinal and bulbar muscular atrophy
Androgen receptor
Cell models
Knock-in mice
Mouse models
Muscle cells
Neuronal cells
Transgenic mice


Ca(2+) and ion channels in hypoxia-mediated pulmonary hypertension.

Abstract: Alveolar hypoxia, a consequence of many lung diseases, can have adverse effects on the pulmonary vasculature. The changes that occur in the pulmonary circulation with exposure to chronic hypoxia include reductions in the diameter of the pulmonary arteries due to structural remodeling of the vasculature. Although the structural and functional changes that occur in the development of pulmonary hypertension have been well investigated, less is known about the cellular and molecular mechanisms of this process. This review will discuss the role of several potassium and calcium channels in hypoxic pulmonary vasoconstriction, both in elevating calcium influx into pulmonary artery smooth muscle cells (PASMCs). In addition to other signal transduction pathways, Ca(2+) signaling in PASMCs plays an important role in the development and progression of pulmonary hypertension due to its central roles in vasoconstriction and vascular remodeling. This review will focus on the effect of chronic hypoxia on ion channels and the potential pathogenic role of Ca(2+) signaling and regulation in the progression of pulmonary hypertension.

chronic hypoxia
Intracellular calcium
calcium regulation
hypoxic pulmonary hypertension
pulmonary vascular smooth muscle


Image correction for diffusion tensor imaging of Rhesus monkey thoracic spinal cord.

Abstract:
BACKGROUND
The relatively tiny spinal cord of non-human primate (NHP) causes increased challenge in diffusion tensor imaging (DTI) post-processing. This study aimed to establish a reliable correction strategy applied to clinical DTI images of NHP.

METHODS
Six normal and partial spinal cord injury (SCI) rhesus monkeys underwent 3T MR scanning. A correction strategy combining multiple iterations and non-rigid deformation was used for DTI image post-processing. Quantitative evaluations were then conducted to investigate effects of distortion correction.

RESULTS
After correction, longitudinal geometric distortion, global distortion, and residual distance errors were all significantly decreased (P < 0.05). Fractional anisotropy at the injured site was remarkably lower than that at the contralateral site (P = 0.0488) and was substantially lower than those at the adjacent superior (P = 0.0157) and inferior (P = 0.0128) areas at the same side.

CONCLUSIONS
Our image correction strategy can improve the quality of the DTI images of NHP thoracic cords, contributing to the development of SCI preclinical research.

Rao|Jia-Sheng|JS|0000-0002-5196-0912 Liu|Zuxiang|Z| Zhao|Can|C| Wei|Rui-Han|RH| Liu|Ruo-Xi|RX| Zhao|Wen|W| Zhou|Xia|X| Tian|Peng-Yu|PY| Yang|Zhao-Yang|ZY| Li|Xiao-Guang|XG|0000-0002-6557-9688

non-human primates
spinal cord injury
image correction strategy
preclinical research


Allergic diseases: the price of civilisational progress.

Abstract: Atopic disorders are a major global health problem. The prevalence of asthma, allergic rhinitis and atopic dermatitis has been increasing over the last four decades, both in the industrialized and developing countries. It seems to be related to changes in the social structure, increasing industrialization, pollution and dietary changes. Many hypotheses link the allergy epidemic to stringent hygiene, dominance of a westernized lifestyle and an accelerated pace of life. Dietary antioxidants, lipids, sodium, vitamin D seem also to be implicated. We endeavour to review the most relevant theories with a special emphasis on the hygiene, antioxidative, lipid and air pollution hypotheses. It is however important to note that none of them explains all the aspects of unprecedented rise in the prevalence of allergic disorders. A complex interplay between host's immune response, invading pathogens, diversity of environmental factors and genetic background seems to be of a particular importance. Current allergy epidemic is multifactorial and basic and epidemiologic studies are warranted to further our understanding of this phenomenon.

Rutkowski|Krzysztof|K| Sowa|Paweł|P| Rutkowska-Talipska|Joanna|J| Sulkowski|Stanisław|S| Rutkowski|Ryszard|R|

allergy epidemic environment genes hypothesis nutrition


Computed tomography enterography for crohn's disease: correlation between the imaging findings and histopathologic scoring system.

Abstract:
OBJECTIVES
The aim of this study was to retrospectively determine if quantitative measurements of computed tomography enterography (CTE) imaging findings correlate with histopathologic scores from biopsy specimens in patients with Crohn's disease (CD).

METHODS
CTE datasets of 34 CD patients (19 male and 15 female) who underwent endoscopy with biopsy within 25 days before or after CTE were retrospectively reviewed. CTE findings of segmental mural hyperenhancement, wall thickening, mural stratification and mesenteric findings were quantitatively measured in the corresponding segment. Histopathologic score of CD was based upon the Naini Cortina scoring system. Correlation between CTE findings and histopathologic scores was assessed using Spearman's rank correlation and logistic or linear regression analysis.

RESULTS
Neutrophilic inflammation contributed the most to the segmental mural hyperenhancement and explained 38.4% of the variance (R2 = 0.384, P = 0.006). Moreover, the increased lymphocytes and plasma cells predicted larger lymph node (P = 0.003) and increased attenuation in mesenteric fat (P = 0.022).

CONCLUSIONS
To a certain extent, macroscopic CTE findings may reflect the microscopic histopathologic state in the inflammatory stage of CD, underscoring that establishment of CTE scoring system may potentially provide an objective tool for assessment of disease progression.

Ma|Liang|L|0000-0003-1297-3283 Shen|Xing|X| Chen|Yi-Jing|YJ| Zhang|Qi|Q| Li|Bo|B| Zhang|Wei|W|

Computed tomography enterography
Histopathologic score
Crohn’s disease


Preclinical study of a self-expanding pulmonary valve for the treatment of pulmonary valve disease.

Abstract: In the past decade, balloon-expandable percutaneous pulmonary valves have been developed and applied in clinical practice. However, all the existing products of pulmonary artery interventional valves in the market have a straight structure design, and they require a preset support frame and balloon expansion. This shape design of the valve limits the application range. In addition, the age of the population with pulmonary artery disease is generally low, and the existing products cannot meet the needs of anti-calcification properties and valve material durability. In this study, through optimization of the support frame and leaflet design, a self-expanding pulmonary valve product with a double bell-shaped frame was designed to improve the match of the valve and the implantation site. A loading and deployment study showed that the biomaterial of the valve was not damaged after being compressed. Pulsatile flow and fatigue in vitro tests showed that the fabricated pulmonary valve met the hydrodynamic requirements after 2 × 108 accelerated fatigue cycles. The safety and efficacy of the pulmonary valve product were demonstrated in studies of pulmonary valve implantation in 11 pigs. Angiography and echocardiography showed that the pulmonary valves were implanted in a good position, and they had normal closure and acceptable valvular regurgitation. The 180 days' implantation results showed that the calcium content was 0.31-1.39 mg/g in the anti-calcification treatment group, which was significantly lower than that in the control valve without anti-calcification treatment (16.69 mg/g). Our new interventional pulmonary valve product was ready for clinical trials and product registration.

Kuang|Dajun|D| Lei|Yang|Y|0000-0003-1461-8111 Yang|Li|L| Wang|Yunbing|Y|

preclinical
self-expanding
pulmonary valve
anti-calcification
double bell-shaped


Sequence and Spatiotemporal Expression Analysis of CLE-Motif Containing Genes from the Reniform Nematode (Rotylenchulus reniformis Linford & Oliveira).

Abstract: The reniform nematode, Rotylenchulus reniformis, is a sedentary semi-endoparasitic species with a host range that encompasses more than 77 plant families. Nematode effector proteins containing plant-ligand motifs similar to CLAVATA3/ESR (CLE) peptides have been identified in the Heterodera, Globodera, and Meloidogyne genera of sedentary endoparasites. Here, we describe the isolation, sequence analysis, and spatiotemporal expression of three R. reniformis genes encoding putative CLE motifs named Rr-cle-1, Rr-cle-2, and Rr-cle-3. The Rr-cle cDNAs showed >98% identity with each other and the predicted peptides were identical with the exception of a short stretch of residues at the carboxy(C)-terminus of the variable domain (VD). Each RrCLE peptide possessed an amino-terminal signal peptide for secretion and a single C-terminal CLE motif that was most similar to Heterodera CLE motifs. Aligning the Rr-cle cDNAs with their corresponding genomic sequences showed three exons with an intron separating the signal peptide from the VD and a second intron separating the VD from the CLE motif. An alignment of the RrCLE1 peptide with Heterodera glycines and Heterodera schachtii CLE proteins revealed a high level of homology within the VD region associated with regulating in planta trafficking of the processed CLE peptide. Quantitative RT-PCR (qRT-PCR) showed similar expression profiles for each Rr-cle transcript across the R. reniformis life-cycle with the greatest transcript abundance being in sedentary parasitic female nematodes. In situ hybridization showed specific Rr-cle expression within the dorsal esophageal gland cell of sedentary parasitic females.

Wubben|Martin J|MJ|
Gavilano|Lily|L|
Baum|Thomas J|TJ|
Davis|Eric L|EL|

reniform nematode
Rotylenchulus
effector
CLE
host-parasite relationship


Antimicrobial activity of plant extracts against sexually transmitted pathogens.

Abstract: Comprehensive management of sexually transmitted infections (STIs) using vaginal or rectal microbicide-based intervention is one of the strategies for prevention of HIV infection. Herbal products have been used for treating STIs traditionally. Herein, we present in vitro activity of 10 plant extracts and their 34 fractions against three sexually transmitted/reproductive tract pathogens - Neisseria gonorrhoeae, Haemophilus ducreyi and Candida albicans. The plant parts were selected; the extracts/fractions were prepared and screened by disc diffusion method. The minimum inhibitory and minimum cidal concentrations were determined. The qualitative phytochemical analysis of selected extracts/fractions showing activity was performed. Of the extracts/fractions tested, three inhibited C. albicans, ten inhibited N. gonorrhoeae and five inhibited H. ducreyi growth. Our study demonstrated that Terminalia paniculata Roth. extracts/fractions inhibited growth of all three organisms. The ethyl acetate fraction of Syzygium cumini Linn. and Bridelia retusa (L.) Spreng. extracts was found to inhibit N. gonorrhoeae at lowest concentrations.

Jadhav|Nutan|N| Kulkarni|Sangeeta|S| Mane|Arati|A| Kulkarni|Roshan|R| Palshetker|Aparna|A| Singh|Kamalinder|K| Joshi|Swati|S| Risbud|Arun|A| Kulkarni|Smita|S|

D000890:Anti-Infective Agents
D002176:Candida albicans
D006191:Haemophilus ducreyi
D008826:Microbial Sensitivity Tests
D009344:Neisseria gonorrhoeae
D010936:Plant Extracts
D027842:Syzygium
D029766:Terminalia

Neisseria gonorrhoeae
Haemophilus ducreyi
Candida albicans
anti-STI activity
microbicide
plant extracts/fractions


Counterintuitive Pseudoscience Propagates by Exploiting the Mind's Communication Evaluation Mechanisms.

Abstract: Epidemiological models of culture posit that the prevalence of a belief depends in part on the fit between that belief and intuitions generated by the mind's reliably developing architecture. Application of such models to pseudoscience suggests that one route via which these beliefs gain widespread appeal stems from their compatibility with these intuitions. For example, anti-vaccination beliefs are readily adopted because they cohere with intuitions about the threat of contagion. However, other varieties of popular pseudoscience such as astrology and parapsychology contain content that violates intuitions held about objects and people. Here, we propose a pathway by which "counterintuitive pseudoscience" may spread and receive endorsement. Drawing on recent empirical evidence, we suggest that counterintuitive pseudoscience triggers the mind's communication evaluation mechanisms. These mechanisms are hypothesized to quarantine epistemically-suspect information including counterintuitive pseudoscientific concepts. As a consequence, these beliefs may not immediately update conflicting intuitions and may be largely restricted from influencing behavior. Nonetheless, counterintuitive pseudoscientific concepts, when in combination with intuitively appealing content, may differentially draw attention and memory. People may also be motivated to seek further information about these concepts, including by asking others, in an attempt to reconcile them with prior beliefs. This in turn promotes the re-transmission of these ideas. We discuss how, during this information-search, support for counterintuitive pseudoscience may come from deference to apparently authoritative sources, reasoned arguments, and the functional outcomes of these beliefs. Ultimately, these factors promote the cultural success of counterintuitive pseudoscience but explicit endorsement of these concepts may not entail tacit commitment.

pseudoscience
astrology
parapsychology
memory
counterintuitive concepts
epidemiology of representations
epistemic vigilance
social transmission


Decreased resting-state brain signal complexity in patients with mild cognitive impairment and Alzheimer's disease: a multiscale entropy analysis.

Abstract: Multiscale entropy (MSE) analysis is a novel entropy-based analysis method for quantifying the complexity of dynamic neural signals and physiological systems across multiple temporal scales. This approach may assist in elucidating the pathophysiologic mechanisms of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Using resting-state fNIRS imaging, we recorded spontaneous brain activity from 31 healthy controls (HC), 27 patients with aMCI, and 24 patients with AD. The quantitative analysis of MSE revealed that reduced brain signal complexity in AD patients in several networks, namely, the default, frontoparietal, ventral and dorsal attention networks. For the default and ventral attention networks, the MSE values also showed significant positive correlations with cognitive performances. These findings demonstrated that the MSE-based analysis method could serve as a novel tool for fNIRS study in characterizing and understanding the complexity of abnormal cortical signals in AD cohorts.

Li|Xuanyu|X| Zhu|Zhaojun|Z| Zhao|Weina|W| Sun|Yu|Y| Wen|Dong|D| Xie|Yunyan|Y| Liu|Xiangyu|X| Niu|Haijing|H| Han|Ying|Y|

(170.2655) Functional monitoring and imaging

(170.3880) Medical and biological imaging


Precision measurement of the Newtonian gravitational constant.

Abstract: The Newtonian gravitational constant G, which is one of the most important fundamental physical constants in nature, plays a significant role in the fields of theoretical physics, geophysics, astrophysics and astronomy. Although G was the first physical constant to be introduced in the history of science, it is considered to be one of the most difficult to measure accurately so far. Over the past two decades, eleven precision measurements of the gravitational constant have been performed, and the latest recommended value for G published by the Committee on Data for Science and Technology (CODATA) is (6.674 08 ± 0.000 31) × 10-11 m3 kg-1 s-2 with a relative uncertainty of 47 parts per million. This uncertainty is the smallest compared with previous CODATA recommended values of G; however, it remains a relatively large uncertainty among other fundamental physical constants. In this paper we briefly review the history of the G measurement, and introduce eleven values of G adopted in CODATA 2014 after 2000 and our latest two values published in 2018 using two independent methods.

Xue|Chao|C| Liu|Jian-Ping|JP| Li|Qing|Q| Wu|Jun-Fei|JF| Yang|Shan-Qing|SQ| Liu|Qi|Q| Shao|Cheng-Gang|CG| Tu|Liang-Cheng|LC| Hu|Zhong-Kun|ZK| Luo|Jun|J|

precision measurement
Newtonian gravitational constant
CODATA


Plants as Antileishmanial Agents: Current Scenario.

Abstract: Leishmaniasis is a clinical manifestation caused by the parasites of the genus Leishmania. Plants are reservoirs of bioactive compounds, which are known to be chemically balanced, effective and least injurious as compared with synthetic medicines. The current resistance and the toxic effects of the available drugs have brought the trend to assess the antileishmanial effect of various plant extracts and their purified compound/s, which are summarized in this review. Moreover, it also highlights various traditional remedies used by local healers against leishmaniasis. A systematic cross-sectional study for antileishmanial activity of natural products was carried out using multiple literature databases. The records retrieved since 2000 till year 2016 were analysed and summarized in the form of comprehensive tables and graphs. Natural products are potential source of new and selective agents that can significantly contribute to primary healthcare and probably are promising substitutes of chemicals for the treatment of protozoan diseases like leishmaniasis. Where the researchers prefer to use alcoholic solvents for the extraction of antileishmanial agents from plants, most of the studies are limited to in vitro conditions majorly on using promastigote forms of Leishmania. Thus, there is a need to carry out such activities in vivo and in host macrophages. Further, there is a need of mechanistic studies that can help taking few of the promising pure compounds to clinical level. Copyright © 2016 John Wiley & Sons, Ltd.

Ullah|Nazif|N| Nadhman|Akhtar|A| Siddiq|Sumaira|S| Mehwish|Shaila|S| Islam|Arshad|A| Jafri|Laila|L| Hamayun|Muhammad|M|

antileishmanial
leishmania
natural products
medicinal plants


Introducing Rhode Island's Health Equity Zones.

Abstract: Many social and environmental factors contribute to the health - and unhealthiness - of a community, and the mix of these factors varies widely from one community to another. A persistent challenge to public health is just how to address so many variables, in so many combinations, in so many diverse communities. The Rhode Island Department of Health is exploring an innovative approach, its Health Equity Zone Initiative, to meet this challenge. [Full article available at http://rimed.org/rimedicaljournal-2016-11.asp].

D000069576:Health Equity
D054625:Healthcare Disparities
D006801:Humans
D011634:Public Health
D012111:Residence Characteristics
D012237:Rhode Island

Health Equity Zones
HEZs
health inequities
healthy communities


Unique genomic features and prognostic value of COSMIC mutational signature 4 in lung adenocarcinoma and lung squamous cell carcinoma.

Abstract:
Background
Analysis of mutational signatures is becoming routine in cancer genomics, with implications for pathogenesis, classification, and prognosis. Among the signatures cataloged at COSMIC, mutational signature 4 has been linked to smoking. However, the distribution of signature 4 in Chinese lung cancer patients has not been evaluated, and its clinical value has not been evaluated. Here we survey mutational signatures in Chinese lung cancer patients and explore the relationship between signature 4 and other genomic features in the patients.

Methods
We extracted mutational signatures from whole-exome sequencing data of Chinese non-small cell lung cancer patients. The data included 401 lung adenocarcinoma (LUAD) and 92 squamous cell carcinoma (LUSC). We then performed statistical analysis to search for genomic and clinical features that can be linked to mutation signatures.

Results
We found signature 4 is the most frequent mutational signature in LUSC and the second most frequent in LUAD. Fifty-six LUAD and thirty-five LUSC patients were named with high signature 4 similarities (cosine similarity >0.7). These patients have shorter survival and higher tumor mutational burden comparing to those with low signature 4 similarities. Dozens of genes with single nucleotide variation, index mutations, and copy number variations were differentially enriched in the patients with high signature 4 similarities. Among these genes, CSMD3, LRP1B, TP53, SYNE1, SLIT2, FGF4, and FGF19 are common in both LUADs and LUSCs with high signature 4 similarities, showing that these genes are tightly associated with signature 4.

Conclusions
The present study is the first to report a comparison in Chinese NSCLC patients with or without COSMIC mutational signature 4. These results will help find the Signature 4 related mutational process in NSCLC.

Cai|Xiuyu|X| Chen|Zhenghe|Z| Deng|Meiling|M| Li|Zhiyong|Z| Wu|Qianchao|Q| Wei|Jinwang|J| Dai|Chun|C| Wang|Guan|G| Luo|Chun|C|

mutational signature 4
Lung adenocarcinoma (LUAD)
lung squamous cell carcinoma (LUSC)


Nanocrystalline Precursors for the Co-Assembly of Crack-Free Metal Oxide Inverse Opals.

Abstract: Inorganic microstructured materials are ubiquitous in nature. However, their formation in artificial self-assembly systems is challenging as it involves a complex interplay of competing forces during and after assembly. For example, colloidal assembly requires fine-tuning of factors such as the size and surface charge of the particles and electrolyte strength of the solvent to enable successful self-assembly and minimize crack formation. Co-assembly of templating colloidal particles together with a sol-gel matrix precursor material helps to release stresses that accumulate during drying and solidification, as previously shown for the formation of high-quality inverse opal (IO) films out of amorphous silica. Expanding this methodology to crystalline materials would result in microscale architectures with enhanced photonic, electronic, and catalytic properties. This work describes tailoring the crystallinity of metal oxide precursors that enable the formation of highly ordered, large-area (mm2 ) crack-free titania, zirconia, and alumina IO films. The same bioinspired approach can be applied to other crystalline materials as well as structures beyond IOs.

inverse opals
self-assembly
metal oxide nanocrystals


LUNATE DISLOCATION: PRESENTATION OF TWO CASES OF A RARE CONDITION.

Abstract: Lunate dislocation is a circumambient disruption of the lunate bone. It is an uncommon but devastating wrist injury that can have negative effect on lifestyle with significant morbidity. This injury can go unrecognized by physicians resulting in complications including but not limited to carpal tunnel syndrome and Kienbock's disease. We present two cases of type 4 lunate dislocation that presented within 24 hours of injury; one had fallen off a moving motorcycle while the other had been involved in a motor vehicle accident. The second developed carpal tunnel syndrome. Radiographs showed typical appearances. Both had Open Reduction with Internal Fixation (ORIF), recovered well, and had good function at the outpatient follow-up.

Onuoha|K M|KM|
Ajiboye|O K|OK|
Bassey|A E|AE|

Lunate dislocation
open reduction
Terry-Thomas sign
spilled tea-cup sign


Kidney transplantation from a living donor to a mentally disabled recipient with bilateral angiomyolipomas-A case report.

Abstract:
INTRODUCTION
Many centers do not perform transplantation in mentally disabled people. Our patient with progressive psychomotor developmental delay had bilateral angiomyolipomas.

PRESENTATION OF THE CASE
Three years ago she underwent a right nephrectomy for massive spontaneous hemorrhage. The left kidney had a large, well-vascularized angiomyolipoma ready at any moment to bleed spontaneously was functioning normally. Two renal transplantation centers in Croatia refused to transplant from the patient's donor mother. The transplantation team had concerns whether to transplant a kidney to a person unable to care for herself, about who would take complete care of the patient, including regular immunosuppressive therapy, and whether it was ethically justified to explant a functioning kidney, although affected by angiomyolipomas, from a patient who required no renal replacement therapy at the time.

CONCLUSION
We presented a successful kidney transplant in a mentally disabled person, clinical and ethical justifications for such a procedure, and a four-year post-transplant evaluation. Furthermore, in our opinion, renal transplantation in the mentally challenged needs to be referred to in literature exclusively as a relative contraindication instead of an absolute one, as has been practiced to date. This would facilitate transplantation teams deciding on kidney transplantation in mentally incapacitated individuals.

Vidas|Željko|Ž| Jurenec|Franjo|F| Lovrić|Eva|E| Samardžija|Marko|M|

Kidney transplantation
Angiomyolipoma
Living related donors
Mentally disabled transplant recipient


The deep circumflex iliac artery perforator flap (DCIAP)--a reconstructive option for the large composite oro-mandibular cutaneous defect.

Abstract: The deep circumflex iliac artery (DCIA) flap is often used for mandibular reconstruction but it is bulky and causes additional donor-site morbidity because of the inclusion of an "obligatory internal oblique muscle". Large composite segmental mandibular resections that consist of floor of mouth, subtotal tongue, and adjacent facial skin are a challenge in terms of reconstruction. They often require 2 free flaps or a free scapular flap and both have disadvantages. The deep circumflex iliac artery perforator (DCIAP) flap with a cutaneous component overcomes the disadvantages. We describe reconstructions with DCIAP flaps in 3 patients with large mandibular composite segmental defects. We report our experience of the flap and discuss some of the difficulties we encountered and the points we learned perioperatively.

Bisase|Brian|B|
Sloane|James|J|
Coombes|Darryl M|DM|
Norris|Paul M|PM|

Perforator flap
Oro-mandibular cutaneous defect
Chimeric
Deep circumflex iliac artery free flap
Glossomandibular defect


Development of hospital information systems: user participation and factors affecting it.

Abstract:
INTRODUCTION
Given the large volume of data generated in hospitals, in order to efficiently management them; using hospital information system (HIS) is critical. User participation is one of the major factors in the success of HIS that in turn leads Information needs and processes to be correctly predicted and also their commitment to the development of HIS to be augmented. The purpose of this study is to investigate the participation rate of users in different stages of HIS development as well as to identify the factors affecting it.

METHOD AND MATERIALS
This is a descriptive-cross sectional study which was inducted in 2014. The study population consists of 140 HIS users (from different types of job including physicians, nurses, laboratory, radiology and HIM staffs) from Teaching Hospitals Affiliated to Urmia University of Medical Sciences. Data were collected using a self-structured questionnaire which was estimated as both reliable and valid. The data were analyzed by SPSS software descriptive statistics and analytical statistics (t-test and chi-square).

RESULTS
The highest participation rate of users in the four-stage development of the HIS was related to the implementation phase (2.88) and the lowest participation rate was related to analysis (1.23). The test results showed that the rate of user participation was not satisfactory in none of the stages of development (P< 0.05). The most important factors in increasing user participation include established teamwork from end-users and the support of top managers from HIS development.

CONCLUSION
According to the results obtained from the study, it seems that health care administrators must have a detailed plan for user participation prior to the development and purchase of HIS so that they identify the real needs as well as increase their commitment and motivations to develop, maintain and upgrade the system, and in this way, the success of the system will be assured.

development
Hospital information systems
user participation
implementation
analysis
design
evaluation


7-Ketocholesterol Promotes Oxiapoptophagy in Bone Marrow Mesenchymal Stem Cell from Patients with Acute Myeloid Leukemia.

Abstract: 7-Ketocholesterol (7-KC) is a cholesterol oxidation product with several biological functions. 7-KC has the capacity to cause cell death depending on the concentration and specific cell type. Mesenchymal stem cells (MSCs) are multipotent cells with the ability to differentiate into various types of cells, such as osteoblasts and adipocytes, among others. MSCs contribute to the development of a suitable niche for hematopoietic stem cells, and are involved in the development of diseases, such as leukemia, to a yet unknown extent. Here, we describe the effect of 7-KC on the death of bone marrow MSCs from patients with acute myeloid leukemia (LMSCs). LMSCs were less susceptible to the death-promoting effect of 7-KC than other cell types. 7-KC exposure triggered the extrinsic pathway of apoptosis with an increase in activated caspase-8 and caspase-3 activity. Mechanisms other than caspase-dependent pathways were involved. 7-KC increased ROS generation by LMSCs, which was related to decreased cell viability. 7-KC also led to disruption of the cytoskeleton of LMSCs, increased the number of cells in S phase, and decreased the number of cells in the G1/S transition. Autophagosome accumulation was also observed. 7-KC downregulated the SHh protein in LMSCs but did not change the expression of SMO. In conclusion, oxiapoptophagy (OXIdative stress + APOPTOsis + autophagy) seems to be activated by 7-KC in LMSCs. More studies are needed to better understand the role of 7-KC in the death of LMSCs and the possible effects on the SHh pathway.

bone marrow
mesenchymal stem cell
acute myeloid leukemia
7-KC
apoptosis
autophagy
oxysterol


Identification of Down-Regulated Proteome in Saccharomyces cerevisiae with the Deletion of Yeast Cathepsin D in Response to Nitrogen Stress.

Abstract: Vacuolar proteinase A (Pep4p) is required for the post-translational precursor maturation of vacuolar proteinases in Saccharomyces cerevisiae, and important for protein turnover after oxidative damage. The presence of proteinase A in brewing yeast leads to the decline of beer foam stability, thus the deletion or inhibition of Pep4p is generally used. However, the influence of Pep4p deletion on cell metabolism in Saccharomyces cerevisiae is still unclear. Herein, we report the identification of differentially down-regulated metabolic proteins in the absence of Pep4p by a comparative proteomics approach. 2D-PAGE (two-dimensional polyacrylamide gel electrophoresis) presented that the number of significantly up-regulated spots (the Pep4p-deficient species versus the wild type) was 183, whereas the down-regulated spots numbered 111. Among them, 35 identified proteins were differentially down-regulated more than 10-fold in the Pep4p-deficient compared to the wild-type species. The data revealed that Pep4p was required for the synthesis and maturation of several glycolytic enzymes and stress proteins, including Eno2p, Fba1p, Pdc1p, Tpi1p, Ssa1, Hsp82p, and Trr1p. The transcription and post-translational modifications of glycolytic enzymes like Eno2p and Fba1p were sensitive to the absence of Pep4p; whereas the depletion of the pep4 gene had a negative impact on mitochondrial and other physiological functions. The finding of this study provides a systematic understanding that Pep4p may serve as a regulating factor for cell physiology and metabolic processes in S. cerevisiae under a nitrogen stress environment.

Hu|Jingjin|J| Yu|Lingxiao|L| Shu|Qin|Q| Chen|Qihe|Q|

proteomics
Saccharomyces cerevisiae
glycolytic enzymes
cellular metabolism
yeast cathepsin D (Pep4p)


Folic acid supplementation acts as a chemopreventive factor in tumorigenesis of hepatocellular carcinoma by inducing H3K9Me2-dependent transcriptional repression of LCN2.

Abstract: The effects and mechanisms of folic acid (FA) as a chemopreventive agent for tumorigenesis of hepatocellular carcinoma (HCC) remain unclear. In this study, the QSG-7701, a human normal liver cell line, was cultured in different FA levels (High, Normal or No) for 6 months. Then, the biological characteristics, the expression of main stem cell-like genes or epithelial-mesenchymal transition (EMT) related genes and the tumorigenicity in vivo of cells cultured in different treatment groups were detected. Our results showed that No FA improved the malignant transformation of cells but High FA depressed the malignant transformation. Meanwhile, cells in different treatment groups were mapped by transcriptome sequencing. Then the relativity of increased LCN2 and decreased FA level was identified and confirmed in vitro and vivo. We also revealed that intracellular control of LCN2 would recover the effects of FA on cell proliferation, cell cycle and tumor formation in vitro and vivo. Finally, our studies displayed that increased FA level induced the down-regulation of LCN2 not by DNA hypermethylation of LCN2 promoter but by promoting the level of histone H3 lysine 9 di-methylation (H3K9Me2) in LCN2 promoter. In conclusion, our studies disclosed the chemopreventive effect of FA supplementation on hepatocarcinogenesis, which partial attributed to the inhibition of LCN2 by regulating histone methylation in promoter. Our results provide a potential mechanism of the chemoprevention of FA supplementation on tumorigenesis of HCC and may be helpful in developing treatment target against HCC.

Zhang|Yin-Ling|YL| Xue|Geng|G| Miao|Hui|H| Zhou|Chuan-Chuan|CC| Sun|Shu-Han|SH| Zhang|Yi|Y|


Anatomic study of pedicled bipolar teres major transfer for irreparable posterosuperior rotator cuff tears.

Abstract:
BACKGROUND
Treatment of rotator cuff (RC) tears has not included bipolar muscle-tendon transfers to date. The objective of this study was to verify the feasibility of pedicled bipolar teres major (TM) transfer over and under the long head of the triceps brachii (LHT) and compare its versatility with monopolar transfer in a model of supraspinatus (SS) tears in cadavers.

METHODS
In 6 shoulders of cryopreserved cadavers, we re-created complete SS tears, conducting monopolar and bipolar TM transfers over and under LHT. We compared the morphology of the SS and TM, defect coverage, angle between the transferred TM and major SS axis, and axillary nerve overlap with each technique.

RESULTS
The TM and SS were morphologically similar. Defect coverage was significantly lower with monopolar transfer (12 ± 4 mm) than with bipolar transfer (39 ± 9 mm under the LHT, P = .003, and 38 ± 8 mm over the LHT, P = .004). The bipolar transfer course over the LHT was the nearest to the SS axis (39° ± 11°, P = .005). We found a greater axillary nerve overlap with bipolar transfer under the LHT (27 ± 8 mm) than with bipolar transfer over the LHT (1 ± 2 mm, P = .005) or monopolar transfer (0 mm, P < .001).

CONCLUSION
Bipolar TM transfer is possible without neurovascular pedicle interference, obtaining greater RC defect coverage and the closest path to the SS axis when conducted over the LHT compared with monopolar or bipolar transfer under the LHT. Accordingly, it can be considered an alternative option for the treatment of posterosuperior RC defects.

Hernández-Cortés|Pedro|P| Rivadeneira-Ruiz|María|M| O'Valle|Francisco|F| Sánchez-Montesinos|Indalecio|I| Roda|Olga|O|

irreparable
shoulder
Rotator cuff injuries
supraspinatus muscle
tendon transfer
teres major muscle


Changes in heart rate variability during anaesthesia induction using sevoflurane or isoflurane with nitrous oxide.

Abstract:
BACKGROUND
The purpose of this study was to compare cardiac sympathetic and parasympathetic balance using heart rate variability (HRV) during induction of anaesthesia between sevoflurane and isoflurane in combination with nitrous oxide.

METHODS
40 individuals aged from 30 to 60 years, scheduled for general anaesthesia were equally divided into sevoflurane or isoflurane groups. After 100% oxygen inhalation for a few minutes, anaesthesia was induced with nitrous oxide 3 L min-1, oxygen 3 L min-1 and sevoflurane or isoflurane. Sevoflurane or isoflurane concentration was increased by 0.5% every 2 to 3 breaths until 5% was attained for sevoflurane, or 3% for isoflurane. Vecuronium was administered to facilitate tracheal intubation. After intubation, sevoflurane was set to 2% while isoflurane was set to 1% with nitrous oxide with oxygen (1:1) for 5 min.

RESULTS
Both sevoflurane and isoflurane provoked a decrease in blood pressure, total power, the low frequency component (LF), and high frequency component (HF) of HRV. Although the heart rate increased during isoflurane anaesthesia, it decreased under sevoflurane. The power of LF and HF also decreased in both groups. LF was higher in the isoflurane group while HF was higher in the sevoflurane group. The LF/HF ratio increased transiently in the isoflurane group, but decreased in the sevoflurane group.

CONCLUSION
Anaesthesia induction with isoflurane-nitrous oxide transiently increased cardiac sympathetic activity, while sevoflurane-nitrous oxide decreased both cardiac sympathetic and parasympathetic activities. The balance of cardiac parasympathetic/sympathetic activity was higher in sevoflurane anaesthesia.

heart rate variability
induction
sevoflurane
isoflurane
general anaesthesia
autonomic nervous system
volatile
volatile anaesthetics


Design and Printing Strategies in 3D Bioprinting of Cell-Hydrogels: A Review.

Abstract: Bioprinting is an emerging technology that allows the assembling of both living and non-living biological materials into an ideal complex layout for further tissue maturation. Bioprinting aims to produce engineered tissue or organ in a mechanized, organized, and optimized manner. Various biomaterials and techniques have been utilized to bioprint biological constructs in different shapes, sizes and resolutions. There is a need to systematically discuss and analyze the reported strategies employed to fabricate these constructs. We identified and discussed important design factors in bioprinting, namely shape and resolution, material heterogeneity, and cellular-material remodeling dynamism. Each design factors are represented by the corresponding process capabilities and printing parameters. The process-design map will inspire future biomaterials research in these aspects. Design considerations such as data processing, bio-ink formulation and process selection are discussed. Various printing and crosslinking strategies, with relevant applications, are also systematically reviewed. We categorized them into 5 general bioprinting strategies, including direct bioprinting, in-process crosslinking, post-process crosslinking, indirect bioprinting and hybrid bioprinting. The opportunities and outlook in 3D bioprinting are highlighted. This review article will serve as a framework to advance computer-aided design in bioprinting technologies.

3D bioprinting
biomaterials
3D printing
additive manufacturing
hydrogels


Cohabitation, post-conception unions, and the rise in nonmarital fertility.

Abstract: The majority of U.S. nonmarital births today are to cohabiting couples. This study focuses on transitions to cohabitation or marriage among pregnant unmarried women during the period between conception and birth. Results using the newly-released 2006-2010 National Survey of Family Growth show that nonmarital pregnancy is a significant precursor to cohabitation before childbirth (18%), exceeding transitions to marriage (5%) by factor of over three. For pregnant women, the boundaries between singlehood, cohabitation, and marriage are highly fluid. The results also reveal substantial variation in post-conception cohabiting and marital unions; e.g., disproportionately low percentages of black single and cohabiting women transitioned into marriage, even when conventional social and economic risk factors are controlled. The multivariate analyses also point to persistent class differences in patterns of family formation, including patterns of cohabitation and marriage following conception. Poorly educated women, in particular, are much more likely to become pregnant as singles living alone or as partners in cohabiting unions. But compared with college-educated women, pregnancies are less likely to lead to either cohabitation or marriage. This paper highlights the conceptual and technical challenges involved in making unambiguous interpretations of nonmarital fertility during a period of rising nonmarital cohabitation.

Lichter|Daniel T|DT|
Sassler|Sharon|S|
Turner|Richard N|RN|

Cohabitation
Nonmarital fertility
Marriage
Childbearing
Shotgun marriage
Union transitions


Trajectories and risk factors for anxiety and depression in children and adolescents with cancer: A 1-year follow-up.

Abstract:
BACKGROUND
There is limited data on the longitudinal trajectories of psychiatric disorders in children with cancer and risk factors for their persistence. The current study aimed to longitudinally assess the trajectories and risk factors for anxiety and depressive symptoms and disorders in children and adolescents with cancer.

METHODS
Children and adolescents with cancer and their parents completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety Module and were interviewed by the semi-structured Affective and Anxiety Modules of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), at 4 time points, 1, 4, 7, and 12 months following the diagnosis of cancer.

RESULTS
Of the 99 patients enrolled, 48% met criteria for anxiety and/or depressive disorders at least once during the follow-up period. There was a significant decrease in PROMIS pediatric and parent anxiety and depression scores (all p's < 0.01) and in the rate of depressive disorders over time (p = 0.02), while rates of anxiety disorders remained stable. Anxiety PROMIS pediatric and parent scores at baseline, having brain tumors and being in the acute treatment phase significantly predicted the presences of anxiety disorders at endpoint.

CONCLUSIONS
Our results highlight the importance of screening for anxiety and disorders in children with cancer, especially among those with brain tumors and at the acute phase of treatment.

Yardeni|Maya|M|0000-0001-8540-9080
Abebe Campino|Gadi|G|
Hasson-Ohayon|Ilanit|I|
Basel|Dana|D|
Hertz-Palmor|Nimrod|N|
Bursztyn|Shira|S|
Weisman|Hana|H|
Pessach|Itai M|IM|
Toren|Amos|A|
Gothelf|Doron|D|

anxiety depression cancer longitudinal PROMIS risk-factors


Influence of contact pressure, cross-shear and counterface material on the wear of PEEK and CFR-PEEK for orthopaedic applications.

Abstract: Total joint replacement is a successful surgical intervention for the treatment of the degeneration of many joints, particularly the hip and knee. As the demand for joint replacement grows, and the life expectancy of the population increases, the performance requirements of these implants also changes. New materials, to improve longevity and enhance performance have been explored including PEEK and CFR-PEEK. This study investigated whether CFR-PEEK and PEEK were appropriate materials for total joint replacement by examining wear performance in simple configuration studies articulating against cobalt chrome under a range of cross-shear and contact pressure conditions. Simple geometry pin on plate studies were conducted for one million cycles for each test condition, with the contact pressure and cross-shear conditions representing a range in which the material may need to operate in-vivo. The wear factor for PEEK was significantly higher than CFR-PEEK and conventional polyethylene under all test conditions. Both PEEK and CFR-PEEK wear were influenced by contact pressure, with the highest wear factors for both materials measured at the highest pressure conditions. PEEK appeared to have a cross-shear dependent wear response, but this was not observed for the CFR-PEEK material. This study has further characterised the wear performance of two materials that are gaining interest for total joint replacement. The wear performance of the PEEK material showed poorer wear performance compared to polyethylene when articulating with a metal counterface, but the performance of the CFR-PEEK material suggested it may provide a suitable alternative to polyethylene in some applications. The wear performance of CFR-PEEK was poorer than polyethylene when it was used as the plate, when there was translation of the contact zone over the surface of the CFR-PEEK plate. This has implications for applications in low conforming contacts, such as lower conformity knee replacement.

Brockett|C L|CL|
Carbone|S|S|
Abdelgaied|A|A|
Fisher|J|J|
Jennings|L M|LM|

Wear PEEK CFR-PEEK Orthopaedics Pin-on-plate


Challenges of recognizing bicuspid aortic valve in elderly patients undergoing TAVR.

Abstract: Recognition of bicuspid aortic valve (BAV) may be challenging in elderly patients with heavily calcified aortic valves undergoing transcatheter aortic valve replacement (TAVR). In this subset, the diagnostic value of pre-procedural echocardiography in clinical routine is unknown. From a total of 2583 patients undergoing TAVR in our center, we determined the rate of BAV detected by routine echocardiography as documented in the medical records. Pre-procedural multidetector computed tomography (MDCT) images were retrospectively analyzed for the presence of BAV and served as reference standard. Using MDCT criteria, BAV was found in 235 (9.1%) (age 80.1 years [interquartile range 76.4; 83.4], 44.3% female). Of these, only 27/235 (11.5%) had been identified as BAV according to echocardiography reports, whereas 6/2348 (0.3%) with TAV had been wrongly diagnosed as BAV (p < 0.001; sensitivity 11.5%, specificity 99.7%). Correct diagnosis of BAV by echocardiography was more likely when transesophageal echocardiography was available (odds ratio (OR) 5.12 [95% confidence interval (CI) 2.22; 11.80]; p < 0.001) and the reader was experienced (OR 5.28 [95% CI 1.55; 18.04]; p = 0.008). Furthermore, correct diagnosis of BAV was more likely in bicommissural-type BAV (OR 2.22 [95% CI 0.90; 5.48]; p = 0.08), whereas heavy aortic valve calcification lead to misdiagnosis (OR 0.39 [95% CI 0.14; 1.06]; p = 0.07). In elderly patients with severe aortic stenosis that are candidates for TAVR, the presence of BAV may be considerably underestimated when relying solely on routine echocardiography. This underlines the value of MDCT for the screening of BAV in this patient population.

D000082882:Bicuspid Aortic Valve Disease

D065467:Transcatheter Aortic Valve Replacement

Bicuspid aortic valve
TAVR
Echocardiography
MDCT
Aortic stenosis


Determinants of smallholder farmers' choice on mulch film thickness in rural China.

Abstract: Agricultural mulch film pollution has become a prevailing concern. Studies have shown that the thickness of mulch film is a key factor affecting mulch film recycling, but research about farmers' choice on mulch film thickness is lacking. Based on survey data from 2025 households in five Chinese provinces in 2018, the Heckman two-stage model was used to analyze the influencing factors of farmers' choice on mulch film thicknesses. Mulch film had been used by 21.98% of the sample households, and 41.47% of the used mulch film did not meet the national thickness standard. The econometric results showed that farmers' product cognition and market factors were the two most important factors, and there was a significant negative correlation with the choice of film thickness. In addition, the choice of mulch film with different thicknesses was affected by household characteristics, subjective norms, and farmland property rights. Strengthening and stabilizing farmland property rights is a long-term mechanism to promote farmers to choose thicker mulch film. In addition to strengthening the production and sale of substandard film supervision, farmers' choice of film thickness should be included in village regulations and other rural grass-roots governance systems, especially in the mechanism design between agricultural farmland protective subsidies and the prevention of mulch film pollution, rather than just considering the recycling itself.

Li|Chang|C| Guo|Jianbing|J| Xu|Xiangbo|X| Sun|Mingxing|M| Zhang|Linxiu|L|

Mulch film thickness
Recycling
Heckman two-stage model
Influencing factors


A New Depsidone from Teloschistes flavicans and the Antileukemic Activity.

Abstract: Lichens produce a variety of secondary metabolites that could be potential sources of pharmaceutically useful chemicals. However, only a limited number of lichen metabolites have been investigated for their biological significance. The objective of this study was to identify the potential compounds responsible for the antileukemic activity of lichen Teloschistes flavicans. Among three fractions (n-hexane, EtOAc, and MeOH-H2O), the ethyl acetate (EtOAc) fraction of T. flavicans methanolic extract showed the strongest inhibition in the HL-60 cell line. Additionally, the EtOAc fraction was further purified to obtain a new depsidone, 2,7-dichloro-3,8-dimethoxy-1,6,9-trimethyl-11H-dibenzo[b,e][1,4]dioxepin-11-one, named as flavicansone, along with rhizonic acid, parietin, and vicanicin. Flavicansone demonstrated the most significant inhibitory action against cell proliferation among the four isolated compounds.

Sanjaya|Angga|A| Avidlyandi|Avidlyandi|A| Adfa|Morina|M| Ninomiya|Masayuki|M| Koketsu|Mamoru|M|

depsidone
Teloschistes flavicans
antileukemic activity
HL-60 cell


Therapeutic targeting of STAT3 with small interference RNAs and antisense oligonucleotides embedded exosomes in liver fibrosis.

Abstract: Hepatic fibrosis is a wound healing response that results in excessive extracellular matrix (ECM) accumulation in response to chronic hepatic injury. Signal transducer and activator of transcription 3 (STAT3) is an important transcription factor associated with the pathogenesis of liver fibrosis. Though a promising potential therapeutic target, there are no specific drug candidates for STAT3. Exosomes are extracellular vesicles generated by all cell types with a capacity to efficiently enter cells across different biological barriers. Here, we utilize exosomes as delivery conduit to specifically target STAT3 in liver fibrosis. Exosomes derived from clinical grade fibroblast-like mesenchymal stem cells (MSCs) were engineered to carry siRNA or antisense oligonucleotide (ASO) targeting STAT3 (iExosiRNA-STAT3 or iExomASO-STAT3 ). Compared to scrambled siRNA control, siRNA-STAT3, or ASO-STAT3, iExosiRNA-STAT3 or iExomASO-STAT3 showed enhanced STAT3 targeting efficiency. iExosiRNA-STAT3 or iExomASO-STAT3 treatments suppressed STAT3 levels and ECM deposition in established liver fibrosis in mice, and significantly improved liver function. iExomASO-Stat3 restored liver function more efficiently when compared to iExosiRNA-STAT3 . Our results identify a novel anti-fibrotic approach for direct targeting of STAT3 with exosomes with immediate translational potential.

Tang|Min|M|
Chen|Yang|Y|
Li|Bingrui|B|
Sugimoto|Hikaru|H|
Yang|Sujuan|S|
Yang|Changqing|C|
LeBleu|Valerie S|VS|
McAndrews|Kathleen M|KM|
Kalluri|Raghu|R|

D000818:Animals
D002251:Carbon Tetrachloride
D055354:Exosomes
D005260:Female
D005786:Gene Expression Regulation
D008103:Liver Cirrhosis
D051379:Mice
D008807:Mice, Inbred BALB C
D016376:Oligonucleotides, Antisense
D034741:RNA, Small Interfering
D050796:STAT3 Transcription Factor
D015398:Signal Transduction

STAT3
liver fibrosis
engineered exosomes
mesenchymal stromal cells


Antidotes for novel oral anticoagulants: current status and future potential.

Abstract: The direct thrombin inhibitor dabigatran and the anti-Xa agents rivaroxaban, edoxaban, and apixaban are a new generation of oral anticoagulants. Their advantage over the vitamin K antagonists is the lack of the need for monitoring and dose adjustment. Their main disadvantage is currently the absence of a specific reversal agent. Dabigatran's, unlike the anti-Xa agents, absorption can be reduced by activated charcoal if administered shortly after ingestion and it can be removed from the blood with hemodialysis. Prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VIIa all show some activity in reversing the anticoagulant effect of these drugs but this is based on ex vivo, animal, and volunteer studies. It is unclear, which, if any, of these drugs is the most suitable for emergency reversal. Three novel molecules (idarucizumab, andexanet, and PER977) may provide the most effective and safest way of reversal. These agents are currently in premarketing studies.

anticoagulants
dabigatran
rivaroxaban
apixaban
prothrombin complex concentrate
factor VIIa
hemorrhage


Influence of renal ischaemia-reperfusion injury on renal neutrophil gelatinase-associated lipocalin receptor (24p3R) in rats.

Abstract: The neutrophil gelatinase-associated lipocalin (NGAL) receptor (24p3R) is expressed in distal nephron and contributes to the endocytosis of NGAL in urine. This study was undertaken to evaluate an influence of renal ischaemia-reperfusion injury on 24p3R. Unilateral renal pedicle was clamped for 0, 10, 20, 30, or 45 minutes in male Wistar rats. Urine was collected for 24 hours after reperfusion, and ischaemic kidney and blood sample were obtained. Apparent histological injury in the ischaemic kidney was detected in the 30 and 45 minutes-treated groups. Urinary NGAL excretion elevated in rats with renal ischaemia for more than 20 minutes, while serum creatinine increased in rats for more than 30 minutes of ischaemia. Renal protein expression of NGAL did not significantly change. Renal mRNA expressions of megalin and cubilin, which are expressed at renal proximal tubules and uptake NGAL, decreased in animals with renal ischaemia for more than 20 minutes. Renal protein expression of 24p3R, which is expressed at renal distal tubules and uptake NGAL, decreased in rats with renal ischaemia for 45 min. This study showed for the first time that renal 24p3R decreased in response to renal ischaemia. As relatively longer renal ischaemia (45 minutes) decreased renal 24p3R protein and increased urinary NGAL excretion, the down-regulation of 24p3R protein might contribute to the elevated urinary excretion of NGAL in rats with unilateral ischaemia-reperfusion injury.

Arakawa|Yusuke|Y| Ushijima|Kentaro|K| Tsuchiya|Hiroyoshi|H| Morishige|Jun-Ichi|JI| Mii|Akiko|A| Ando|Hitoshi|H| Tsuruoka|Shu-Ichi|SI| Fujimura|Akio|A|0000-0002-5160-5777


A novel diphtheria toxin-based bivalent human EGF fusion toxin for treatment of head and neck squamous cell carcinoma.

Abstract: Epidermal growth factor receptor (EGFR) is often overexpressed in head and neck squamous cell carcinoma (HNSCC) and represents a top candidate for targeted HNSCC therapy. However, the clinical effectiveness of current Food and Drug Administration (FDA)-approved drugs targeting EGFR is moderate, and the overall survival rate for HNSCC patients remains low. Therefore, more effective treatments are urgently needed. In this study, we generated a novel diphtheria toxin-based bivalent human epidermal growth factor fusion toxin (bi-EGF-IT) to treat EGFR-expressing HNSCC. Bi-EGF-IT was tested for in vitro binding affinity, cytotoxicity, and specificity using 14 human EGFR-expressing HNSCC cell lines and three human EGFR-negative cancer cell lines. Bi-EGF-IT had increased binding affinity for EGFR-expressing HNSCC compared with the monovalent version (mono-EGF-IT), and both versions specifically depleted EGFR-positive HNSCC, but not EGFR-negative cell lines, in vitro. Bi-EGF-IT exhibited a comparable potency to that of the FDA-approved EGFR inhibitor, erlotinib, for inhibiting HNSCC tumor growth in vivo using both subcutaneous and orthotopic HNSCC xenograft mouse models. When tested in an experimental metastasis model, survival was significantly longer in the bi-EGF-IT treatment group than the erlotinib treatment group, with a significantly reduced number of metastases compared with mono-EGF-IT. In addition, in vivo off-target toxicities were significantly reduced in the bi-EGF-IT treatment group compared with the mono-EGF-IT group. These results demonstrate that bi-EGF-IT is more effective and markedly less toxic at inhibiting primary HNSCC tumor growth and metastasis than mono-EGF-IT and erlotinib. Thus, the novel bi-EGF-IT is a promising drug candidate for further development.

Qi|Zeng|Z|
Qiu|Yue|Y|
Wang|Zhaohui|Z|
Zhang|Huiping|H|
Lu|Ling|L|
Liu|Yanqiu|Y|
Mathes|David|D|
Pomfret|Elizabeth A|EA|
Gao|Dexiang|D|
Lu|Shi-Long|SL|0000-0001-7132-7076
Wang|Zhirui|Z|0000-0002-0046-2294

EGF
fusion toxin
EGFR
HNSCC
diphtheria toxin
head and neck cancer


Genetic Aspects of Hereditary Arrhythmogenic Syndromes in Children and Adults.

Abstract: Recent research has revealed the genetic etiology of a number of heart diseases that cause sudden cardiac death. Lethal channelopathies are of great importance among the genetically determined heart diseases. Their basic characteristics are unpredictable and deadly nature, autosomal dominant inheritance with variable expressivity and incomplete penetrance in structurally normal heart, and absence of morphological and histological clues that a standard autopsy can identify. Minimum screening of the relatives of sudden cardiac death victims involves taking medical history, physical examination, electrocardiography, echocardiography, and exercise testing. Total positivity of classic genetic tests is only 15%-25%. Even the next generation sequencing technology does not provide a positive result of genetic testing in more than 35% of cases. Therefore, it is necessary to identify a larger number of genes the presence of which can lead to sudden cardiac death, to reduce the number of false positive results, and point to the importance of conducting genetic testing of young victims of sudden cardiac death. Until then, it is enough to preserve 5 g of fresh heart tissue of sudden cardiac death victims at a temperature of -80 °C. The material can be analyzed years later without losing its actuality because it contains information important for the next generation of the sudden cardiac death victim relatives.

Heart diseases
Autopsy
Echocardiography
Genetic testing
Death, sudden, cardiac
High-throughput nucleotide sequencing


Efficacy of breast MRI for surgical decision in patients with breast cancer: ductal carcinoma in situ versus invasive ductal carcinoma.

Abstract:
BACKGROUND
Preoperative breast magnetic resonance imaging (MRI) provides more information than mammography and ultrasonography for determining the surgical plan for patients with breast cancer. This study aimed to determine whether breast MRI is more useful for patients with ductal carcinoma in situ (DCIS) lesions than for those with invasive ductal carcinoma (IDC).

METHODS
A total of 1113 patients with breast cancer underwent mammography, ultrasonography, and additional breast MRI before surgery. The patients were divided into 2 groups: DCIS (n = 199) and IDC (n = 914), and their clinicopathological characteristics and oncological outcomes were compared. Breast surgery was classified as follows: conventional breast-conserving surgery (Group 1), partial mastectomy with volume displacement (Group 2), partial mastectomy with volume replacement (Group 3), and total mastectomy with or without reconstruction (Group 4). The initial surgical plan (based on routine mammography and ultrasonography) and final surgical plan (after additional breast MRI) were compared between the 2 groups. The change in surgical plan was defined as group shifting between the initial and final surgical plans.

RESULTS
Changes (both increasing and decreasing) in surgical plans were more common in the DCIS group than in the IDC group (P <  0.001). These changes may be attributed to the increased extent of suspicious lesions on breast MRI, detection of additional daughter nodules, multifocality or multicentricity, and suspicious findings on mammography or ultrasonography but benign findings on breast MRI. Furthermore, the positive margin incidence in frozen biopsy was not different (P = 0.138).

CONCLUSIONS
Preoperative breast MRI may provide more information for determining the surgical plan for patients with DCIS than for those with IDC.

Breast
Ductal carcinoma
Magnetic resonance imaging
Surgical plan


Bipolar spectrum disorders and associated factors among adults attending an antiretroviral therapy clinic in Gedeo zone health centers, southern Ethiopia.

Abstract:
Background
Bipolar spectrum disorders (BPSDs) are more common among HIV-positive individuals than the general population. Although BPSDs have very diverse and devastating consequences (immune suppression, cognitive impairment and poor medication adherence), little is known about BPSDs among HIV-positive individuals in Ethiopia. Therefore, this study was aimed to assess the prevalence and associated factors of BPSDs among adults attending antiretroviral therapy (ART) clinics in Gedeo zone health centers, southern Ethiopia.

Patients and methods
An institutional-based cross-sectional study was conducted by screening 412 randomly selected HIV-positive individuals using Mood Disorder Questionnaire. SPSS version 20 was used for data analysis. Bivariable and multivariable logistic regression models were fitted to identify factors associated with BPSDs. Adjusted OR (AOR) with corresponding 95% CI was computed to determine the association.

Results
Of the total 412 participants, 11.2% were screened positive for BPSDs. Lower CD4 count (AOR =2.97; 95% CI: 1.11, 7.90), past history of mental health problem (AOR =3.35; 95% CI: 1.576, 7.144), poor social support (AOR =2.6; 95% CI: 1.06, 6.63) and poor ART drug adherence (AOR =3.59; 95% CI: 1.78, 7.21) had a positive association with BPSDs.

Conclusion
In this study, the prevalence of BPSDs was high among adult patients attending ART clinics in Gedeo zone health centers. Poor social support, poor ART drug adherence, lower CD4 level and history of mental illness had statistically significant association with BPSDs. This demonstrates a need for the integration of Mental Health and Psycho Social Support with HIV/AIDS care services. Moreover, establishing good social support and controlling ART adherence were found to be very crucial too.

Belayneh|Zelalem|Z| Alemu|Wagaye|W| Mekuriaw|Birhanie|B| Abebe|Zegeye|Z|

bipolar spectrum disorder
Gedeo
Ethiopia
mood disorders
mental health
HIV/AIDS
Dilla


Diffuse intra-abdominal splenosis presenting as carcinomatosis exhibiting positron emitted tomography hypermetabolic activity.

Abstract: •Splenosis can mimic carcinomatosis upon many imaging modalities.•History of splenectomy must be considered when evaluating carcinomatosis.•Scintigraphy is the preferred for confirming the presence of splenosis.

Kellert|Brian|B|
Caster|Michelle|M|
Des Jean|Ryan|R|
Vaccarello|Luis|L|


Chemerin predicts carotid intima-media thickening in severe obesity.

Abstract:
BACKGROUND AND AIMS
Chemerin is an adipokine with an emerging role in the crosstalk between adipose tissue and immune system. It is overexpressed in severe obesity, affects adipogenesis and glucose homeostasis and it correlates with early vascular damage. The aim of this study is to investigate the correlation between circulating levels of chemerin and early vascular damage in subjects with severe obesity, before and after laparoscopic sleeve gastrectomy (LSG).

METHODS
Fifty-six obese subjects eligible for LSG were enrolled in the study. The following parameters were evaluated: body mass index (BMI), glycemia, insulinemia, glycated haemoglobin, lipid profile, plasma chemerin levels and carotid intima-media thickness (cIMT). Fifty-four subjects were evaluated 1 year after the intervention.

RESULTS
Univariate analysis showed a direct and significant correlation between chemerin and waist circumference, insulin resistance, glycated haemoglobin and cIMT. Chemerin was a better predictor of intima-media thickening than waist circumference and glycated haemoglobin at the ROC curve analysis, with a cut-off value for chemerin of 140 ng/mL. The reduction of chemerin is independently associated with the reduction of cIMT and the improvement of insulin sensitivity after LSG.

CONCLUSION
Chemerin is involved in the development and progression of early vascular damage and insulin resistance in subjects with severe obesity, and in their healing after bariatric surgery. Chemerin could also have a role in the assessment of cardiovascular risk in subjects with severe obesity.

chemerin
severe obesity
early vascular damage
carotid IMT
inflammation
macrophages


Genome-Wide Analysis of the Glutathione S-Transferase (GST) Genes and Functional Identification of MdGSTU12 Reveals the Involvement in the Regulation of Anthocyanin Accumulation in Apple.

Abstract: Anthocyanins have essential biological functions, affecting the development of horticultural production. They are synthesized in the cytoplasm through flavonoid metabolic pathways and finally transported into vacuoles for storage. Plant glutathione S-transferases (GSTs) are multifunctional enzymes involved in anthocyanin transportation. In this study, we identified 38 GSTs from the apple (Malus domestica) genome (HFTH1 Whole Genome v1.0) based on the sequence similarity with the GST family proteins of Arabidopsis. These MdGST genes could be grouped into nine chief subclasses: U, F, L, Z, T, GHR, EF1Bγ, TCHQD, and DHAR. The structures, motifs, three-dimensional models, and chromosomal distribution of MdGST genes were further analyzed. Elements which are responsive for some hormones and stress, and others that involve genes related to flavonoid biosynthesis were forecast in the promoter of MdGST. In addition, we identified 32 orthologous gene pairs between apple and Arabidopsis. These genes indicated that numerous apple and Arabidopsis counterparts appeared to be derived from a common ancestor. Amongst the 38 MdGST genes, MdGSTU12 was considerably correlated with anthocyanin variation in terms of extracting expression profiles from reported. Finally, further functional identification in apple transgenic calli and subcellular localization confirmed that MdGSTU12 was of great significance in anthocyanin accumulation in apple.

Zhao|Yu-Wen|YW| Wang|Chu-Kun|CK| Huang|Xiao-Yu|XY| Hu|Da-Gang|DG|

glutathione S-transferase (GST)
MdGSTU12
anthocyanin
apple
gene family


Similarities and differences in the lexical-grammatical relation of young dual language learners with and without specific language impairment.

Abstract: This study examines the lexical-grammatical relation within and across in preschool Latino dual language learners (DLLs) with and without specific language impairment (SLI) using language-specific vocabulary and conceptual lexical-semantic skills. The participants were sixty-one typically developing (TD) Spanish-English speaking DLLs and seventy-four DLLs with SLI from low-income households. Standardized and researcher developed assessment tools were used to measure vocabulary, semantics, and grammar in both Spanish and English. Cross-sectional data were analyzed using hierarchical linear regressions to determine the nature of the lexical-grammatical association within and across languages. The study found significant within-language relations between measures of vocabulary and grammar for both groups. Conceptual vocabulary was a significant predictor for English grammar in both groups. For the SLI group only, both English and Spanish vocabulary scores significantly predicted English grammar and bilingual semantics scores predicted Spanish grammar. These findings underscore the role of language-specific vocabulary on grammatical development and suggest the presence of bilingual bootstrapping in DLLs. However, the degree and nature of cross-linguistic associations vary by language ability and language proficiency. The role of age and nonverbal cognition and clinical implications are also discussed.

Dual language learner
specific language impairment
lexical-grammatical associations
bilingual
sentence repetition task


In vivo and in vitro anti-inflammatory effects of Sophora flavescens residues.

Abstract:
ETHNOPHARMACOLOGICAL RELEVANCE
The dried roots of Sophora flavescens Ait. (Leguminosae) is traditionally used as antipyretic medicine to reduce inflammation. It is well known that alkaloids and flavonoids are the main constituents of S. flavescens. However, the clinical researches and applications of S. flavescens is mainly based on its water-extracted alkaloids, its flavonoids may still remain in residues and have been underused. With development and manufacturing of S. flavescens in recent years, more herb residues are being produced. Since they are typically treated as waste and dumped openly in landfill sites, which can cause pollution, there is a great need to explore these wastes as recyclable resources and increase their added value. To date, whether other bioactive components would be found in the residues of S. flavescens is still unknown. If the extraction method of these active ingredients was established, the residues of S. flavescens could be turned from the harm to a benefit and make great sense of the comprehensive utilization of S. flavescens resources. This study aimed to establish an extraction method of the residues of S. flavescens and investigate the anti-inflammatory effect of it both in vivo and in vitro.

MATERIALS AND METHODS
Dried S. flavescens were decocted with distilled water firstly, then the residues were powdered and extracted with ethyl acetate by using ultrasonic wave. HPLC was utilized to analyze the chemical constituents of the water extracts of S. flavescens (WSF) and the ethyl acetate extracts of residues of S. flavescens (RSF). In vivo, the anti-inflammatory effect of WSF and RSF were evaluated using the xylene-induced auricle edema, acetic acid-induced peritoneal permeability and carrageenan-induced hind paw edema methods. In vitro, the inhibitory activities of WSF and RSF on NO, TNF-α, IL-6 and MCP-1 production of LPS-treated RAW264.7 cells were measured.

RESULTS
The major ingredients of RSF were flavonoids, while WSF almost had no flavonoids. In vivo, WSF and RSF (200 mg/kg) could significantly inhibit the edema in the xylene-induced mice auricle edema and carrageenan-induced hind paw edema as well as the peritoneal permeability increased by acetic acid. They can also lower production levels of PGE2 in inflamed paw tissues. In vitro experimental results showed that RSF (25-100 μg/mL) could significantly inhibit the release of pro-inflammatory cytokines NO, TNF-α, IL-6 and MCP-1 on LPS-induced RAW264.7 cells. The in vitro suppress effect of WSF had no dose-response relationship.

CONCLUSIONS
The residues of S. flavescens had obvious flavonoids with anti-inflammatory activity. This study provided evidence for the reuse of residues from S. flavescens in the food additive, medicine and cosmetic industries.

Ma|Hongyan|H| Huang|Qi|Q| Qu|Wenshan|W| Li|Linyuan|L| Wang|Min|M| Li|Shao|S| Chu|Fujiang|F|

Anti-inflammatory effect
Residues
Sophora flavescens Ait.


The Trend of Targeted Therapies in Chinese Patients With Ankylosing Spondylitis: Results From a Real-Life Survey.

Abstract: Introduction : Targeted medication, including mostly biologics and small-molecule chemical drugs, is an important therapy for ankylosing spondylitis (AS). There are still limited data on the preference of different targeted drugs in Chinese AS patients. Methods : A questionnaire-based cross-sectional study was performed on AS patients from six hospitals in three provinces in South China. Anti-rheumatic diseases' medication history includes the recent and previous usage of biologics or Janus kinase inhibitors (JAKi) in the last complete course of treatment, disease severity, and reasons for targeted-treatment change or preference. Results : 354 of 366 participants responded to the online survey. The participants' median age was 32 years, with a median of 7.3 years of disease duration; 79.7% were male. 63.6% of them were in the course of biologics or JAKi. Generic ETN is the most widely used and willing-to-use biologic though the proportion of its usage shrunk in the present compared with the past. The choice of original-branded ADA demonstrated an increase in usage. The preference of secukinumab and tofacitinib depicted a quick ascending trend. Conclusion : TNF-α inhibitors (TNFi) are still the most popular targeted medication for AS in China. Their price influences patients' preferences mostly. The doctor's recommendation is also part of the equation. Rheumatologists should pay more attention to patients' education to formulate targeted therapeutic plans.

Wen|Yiquan|Y| Hu|Zhuoran|Z| Xie|Baozhao|B| Yuan|Fei|F| Xie|Zhengquan|Z| Jiang|Yutong|Y| Lin|He|H| Qi|Jun|J| Chen|Qiyun|Q|

Chinese
ankylosing spondylitis
biologics
preference
cross-sectional study


Management of acute exacerbations of airways disease: advice for the non-respiratory physician.

Abstract: Airways disease encompasses a number of conditions including asthma and chronic obstructive pulmonary disorder (COPD). In this article we describe the management of patients with acute exacerbations of airways disease.


Anthracycline-induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment.

Abstract: Anthracyclines are highly effective chemotherapeutic agents, used for a wide variety of malignancies. Cardiotoxicity is a well-recognized side effect of anthracycline therapy that limits the total amount of drug administered and can cause heart failure in some patients. Most experimental data support oxidative stress as the etiology of anthracycline-induced cardiotoxicity. The objective of this paper was to provide a review of the clinical classification, risk factors, monitoring and prevention of anthracycline-induced cardiotoxicity in patients with breast cancer.

Cai|Fengfeng|F|
Luis|Manuel Antonio Falar|MAF|
Lin|Xiaoyan|X|
Wang|Minghong|M|
Cai|Lu|L|
Cen|Chunmei|C|
Biskup|Ewelina|E|

cardiotoxicity
treatment
breast cancer
prevention
anthracyclines
risk factors
doxorubicin


Shigella sonnei Does Not Use Amoebae as Protective Hosts.

Abstract: Shigella flexneri and Shigella sonnei bacteria cause the majority of all shigellosis cases worldwide. However, their distributions differ, with S. sonnei predominating in middle- and high-income countries and S. flexneri predominating in low-income countries. One proposed explanation for the continued range expansion of S. sonnei is that it can survive in amoebae, which could provide a protective environment for the bacteria. In this study, we demonstrate that while both S. sonnei and S. flexneri can survive coculture with the free-living amoebae Acanthamoebae castellanii, bacterial growth is predominantly extracellular. All isolates of Shigella were degraded following phagocytosis by A. castellanii, unlike those of Legionella pneumophila, which can replicate intracellularly. Our data suggest that S. sonnei is not able to use amoebae as a protective host to enhance environmental survival. Therefore, alternative explanations for S. sonnei emergence need to be considered.IMPORTANCE The distribution of Shigella species closely mirrors a country's socioeconomic conditions. With the transition of many populous nations from low- to middle-income countries, S. sonnei infections have emerged as a major public health issue. Understanding why S. sonnei infections are resistant to improvements in living conditions is key to developing methods to reduce exposure to this pathogen. We show that free-living amoebae are not likely to be environmental hosts of S. sonnei, as all Shigella strains tested were phagocytosed and degraded by amoebae. Therefore, alternative scenarios are required to explain the emergence and persistence of S. sonnei infections.

D048248:Acanthamoeba castellanii
D004405:Dysentery, Bacillary
D000076662:Host Microbial Interactions
D006801:Humans
D012764:Shigella sonnei

Shigella sonnei
amoeba
intracellular survival


Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial.

Abstract:
BACKGROUND
Cerebral palsy (CP) is a syndrome of childhood movement and posture disorders. Clinical evidence is still limited and sometimes inconclusive about the benefits of human umbilical cord mesenchymal stem cells (hUC-MSCs) for CP. We conducted a randomized trial to evaluate the safety and efficacy of hUC-MSC transplantation concomitant with rehabilitation in patients with CP.

METHODS
Eligible patients were allocated into the hUC-MSC group and control group. In addition to rehabilitation, the patients in the hUC-MSC group received four transfusions of hUC-MSCs intravenously, while the control group received a placebo. Adverse events (AEs) were collected for safety evaluation in the 12-month follow-up phase. Primary endpoints were assessed as activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales. In addition, cerebral metabolic activity was detected by 18F-FDG-PET/CT to explore the possible mechanism of the therapeutic effects. Primary endpoint data were analyzed by ANOVA using SPSS version 20.0.

RESULTS
Forty patients were enrolled, and 1 patient withdrew informed consent. Therefore, 39 patients received treatments and completed the scheduled assessments. No significant difference was shown between the 2 groups in AE incidence. Additionally, significant improvements in ADL, CFA, and GMFM were observed in the hUC-MSC group compared with the control group. In addition, the standard uptake value of 18F-FDG was markedly increased in 3 out of 5 patients from the hUC-MSC group at 12 months after transplantation.

CONCLUSIONS
Our clinical data showed that hUC-MSC transplantation was safe and effective at improving the gross motor and comprehensive function of children with CP when combined with rehabilitation. Recovery of cerebral metabolic activity might play an essential role in the improvements in brain function in patients with CP. The therapeutic window, transfusion route, and dosage in our study were considerable for reference in clinical application.

TRIAL REGISTRATION
Chictr.org.cn, ChiCTR1800016554. Registered 08 June 2018-retrospectively registered. The public title was "Randomized trial of umbilical cord-derived mesenchymal stem cells for cerebral palsy."

Gu|Jiaowei|J| Huang|Li|L| Zhang|Che|C| Wang|Yong|Y| Zhang|Ruibo|R| Tu|Ziliang|Z| Wang|Hengdong|H| Zhou|Xihui|X| Xiao|Zhousheng|Z| Liu|Zegan|Z| Hu|Xiang|X| Ke|Zunchen|Z| Wang|Dabin|D| Liu|Li|L|0000-0003-1200-3068

D045164:Mesenchymal Stem Cell Transplantation

Mesenchymal stem cells
Cell transplantation
Cerebral palsy
Umbilical cord
Activities of daily living
Clinical trial


Safety Results and Analysis of Eribulin Efficacy according to Previous Microtubules-Inhibitors Sensitivity in the French Prospective Expanded Access Program for Heavily Pre-treated Metastatic Breast Cancer.

Abstract:
PURPOSE
Eribulin is approved for advanced breast cancers refractory to anthracyclines and taxanes. Efficacy according to sensitivity to previous therapies has been poorly explored.

Materials and Methods
Safety data were collected prospectively and we retrospectively collected efficacy data from the five French centres that participated in the Eribulin E7389-G000-398 expanded access program. Our main objectiveswere exploration of safety and analysis of eribulin efficacy (progression-free survival [PFS] and overall survival [OS]) according to sensitivity to the last microtubule-inhibiting agent administered.

RESULTS
Median eribulin treatment duration was 3.3 months for the 250 patients included in this prospective single-arm study. Two hundreds and thirty-nine patients (95.6%) experienced an adverse event (AE) related to treatment including 129 (51.6%) with grade ≥ 3 AEs. The most frequently observed toxicities were cytopenias (59.6% of included patients), gastrointestinal disorders (59.2%), and asthenia (56.4%). The most frequent grade 3-4 AE was neutropenia (37.2% with 4.8% febrile neutropenia). Median PFS and OS were 4.6 and 11.8 months, respectively. Patients classified as responders to the last microtubule-inhibiting therapy had a longer OS (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.51 to 0.94; p=0.017), and tended to display a better PFS (HR, 0.78; 95% CI, 0.58 to 1.04; p=0.086). OS improvement was still significant in multivariate analysis (adjusted HR, 0.53; 95% CI, 0.35 to 0.79; p=0.002).

CONCLUSION
This work based on a prospective study suggests that identification of patients likely to be more sensitive to eribulin could be based on their previous response to microtubules inhibitors.

Sabatier|Renaud|R| Diéras|Véronique|V| Pivot|Xavier|X| Brain|Etienne|E| Roché|Henri|H| Extra|Jean-Marc|JM| Monneur|Audrey|A| Provansal|Magali|M| Tarpin|Carole|C| Bertucci|François|F| Viens|Patrice|P| Zemmour|Christophe|C| Gonçalves|Anthony|A|

Safety
Eribulin
Metastatic breast cancer
Survival
Microtubule inhibition


Pilot Model for Community Based Oral Cancer Screening Program: Outcome from 4 Northeastern Provinces in Thailand.

Abstract: Management of advanced-stage oral cancer adds a great burden to individuals and health care systems. Community-based oral cancer screening can be beneficial in early detection and treatment. In this study, a novel oral cancer screening program was conducted utilizing an existing network of health care personnel, facilities, and digital database management for efficient coverage of a large population. The screening program considered 392,396 individuals aged ≥40 from four northeastern provinces in Thailand. Three levels of screening were performed: S1 by village healthcare volunteers to identify risk groups, S2 by dental auxiliaries to visually identify abnormal oral lesions, and S3 by dentists for final diagnosis and management. A total of 349,318 individuals were interviewed for S1, and 192,688 were identified as a risk group. For S2, 88,201 individuals appeared, and 2969 were further referred. Out of 1779 individuals who appeared for S3, oral potentially malignant disorders (OPMDs) were identified in 544, non-OPMDs in 1047, doubtful lesions in 52, and no results in 136 individuals. Final treatment was carried out in 704 individuals that included biopsies of 504 lesions, exhibiting 25 cancerous lesions and 298 OPMDs. This study is so far one of the largest oral cancer screening programs conducted in Thailand and showed effective implementation of community-based oral cancer screening.

D055088:Early Detection of Cancer
D006801:Humans
D008403:Mass Screening
D009059:Mouth Diseases
D009062:Mouth Neoplasms
D013785:Thailand

oral cancer
cancer screening
oral potentially malignant disorders
community screening
village health volunteers


Evaluation of cowpea mini core accessions for resistance to flower bud thrips Megalurothrips sjostedti Trybom (Thysanoptera: Thripidae).

Abstract: The flower bud thrips, Megalurothrips sjostedti Trybom (Thysanoptera: Thripidae), is an economically important pest of cowpea in sub-Saharan Africa. Varietal resistance is the most preferred, environmentally friendly, cost-effective and sustainable option for controlling this pest. The objective of this study was to identify sources of resistance to M. sjostedti among mini core accessions from the largest world cowpea germplasm collection maintained at the International Institute of Tropical Agriculture (IITA). The study was conducted during the 2015 and 2016 cropping seasons where 365 accessions were screened under field conditions. Each accession was rated visually for thrips damage score, flower abortion rate, number of pods per plant and number of thrips per flower. The resistance levels observed in genotypes TVu8631, TVu16368, TVu8671 and TVu7325 were similar to that of the resistant check "Sanzisabinli" (called Sanzi) during both seasons. In addition, 56 mini core genotypes showed moderate resistance to thrips damage. High heritability values were associated with thrips damage scores at 65 days after planting (0.60), percentage of effective peduncles (0.59), flower bud abortion rate (0.59), number of pods per plant (0.51) and number of peduncles with pods (0.5). The accessions identified with good levels of resistance to flower bud thrips will be used in cowpea breeding programs to develop improved resistant varieties.

varietal resistance
heritability
cowpea genotypes
crop improvement
field screening
yield loss


Trajectories of Health Status during the Transition from School to University: Piloting the Method of Biographical Mapping in German Medical Students.

Abstract: Health status and health behavior change during the transition from school to university. However, it is still unclear whether these changes occur at specific points in time, and whether these changes are stable. Therefore, our aim was to conduct a pilot test on biographical mapping (BM) for the first time in this research area in order to map the trajectories of the health status of university students over time. This enabled us to also test the practicability of BM, and to assess the agreement of the findings of BM with those of a standardized questionnaire. We included 30 fourth-year university students. First, they filled in a standardized questionnaire on their sociodemographic information, current health status, and health status compared with that for their final year of school. Second, they filled in a BM grid that allows for drawing the changes in health status that have taken place over the transition period. The health status changed during the transition (e.g., slight decline in general subjective health), and was related to specific events before and after the transition (e.g., examinations), showing that all health variables were not stable over time. The findings of BM were also reflected in the standardized questionnaire. Using BM revealed the changes in health during a six-year-period, including the school-university transition. The identified changes in health during transition and at specific time points underline that not only assistance before the transition, but also psychological support during studies, seems to be important for the health promotion of students. Besides this, BM seems to be a useful, although time-consuming, instrument for which the results were similar to those in the questionnaire.

trajectories
health status
transition
university
students


Optimal method selection for biocompatible extraction of rosmarinic acid from mycorrhizal hairy roots of Ocimum basilicum.

Abstract: Mycorrhizal hairy roots of Ocimum basilicum produce high amount of rosmarinic acid and are also valuable resource of quality mycorrhizal spores. To utilize their potential as continuous resource of biological and biochemical products, an efficient separation method is required. Solvent based extraction methods have a negative impact on mycorrhizal spore viability and vitality. Accordingly, we developed a biocompatible extraction method where spore and root viability is maintained with efficient extraction of rosmarinic acid. We screened temperature- and sonication-assisted techniques in ethanol, methanol, dimethyl sulfoxide, ionic liquid and surfactants. An inverse relationship was found between an increase in temperature and mycorrhizal and root viability. Optimum temperature for extraction was 30 °C. Most suitable solvents were 10% methanol; 0.25 M ionic liquid and dimethyl sulfoxide. Ethanol, nonane, dodecane, Triton X-100 and Tween-20 were not found suitable. Thus, our study sets a platform for optimization studies with mycorrhizal roots of other medicinal plants.

Srivastava|Shivani|S|
Cahill|David M|DM|
Adholeya|Alok|A|

Biocompatible
Rosmarinic acid
Hairy roots
Mycorrhiza
Rhizophagus irregularis


Aqueous chlorination of sulfamethazine and sulfamethoxypyridazine: Kinetics and transformation products identification.

Abstract: Sulfonamides (SNs) are synthetic antimicrobial agents. These substances are continually introduced into the environment, and they may spread and maintain bacterial resistance in the different compartments. The chlorination of 2 SNs, namely, sulfamethazine (SMT) and sulfamethoxypyridazine (SMP), was investigated to study their reactivity with chlorine at typical concentrations for water treatment conditions. Experiments conducted in purified water show an acceleration of SMT and SMP degradation of a factor 1.5 by comparison to drinking water matrix. This difference is due to pH variation and competitive reactions between SNs and mineral and organic compounds, with chlorine in drinking water. In the presence of an excess of chlorine (6.7 μmol·L-1 ) in ultrapure water at pH 7.2, second-order degradation rate constants were equal to 4.5 × 102 M-1 ·s-1 and 5.2 × 102 M-1 ·s-1 for SMT and SMP, respectively. The structures of transformation products were investigated by liquid chromatography tandem mass spectrometry analyses with equimolar concentrations between chlorine and SNs. SO2 elimination, cyclization, and electrophilic substitutions were the main pathways of by-products formation. Moreover, the toxicity of the proposed structures was predicted by using toxicity estimation software tool program. The results indicated that most by-products may present developmental toxicity.

D002851:Chromatography, High Pressure Liquid

chlorination sulfamethazine sulfamethoxypyridazine sulfonamides by-products antibiotics


Cerebellar cortex and cerebellar nuclei are concomitantly activated during eyeblink conditioning: a 7T fMRI study in humans.

Abstract: There are controversies whether learning of conditioned eyeblink responses primarily takes place within the cerebellar cortex, the interposed nuclei, or both. It has also been suggested that the cerebellar cortex may be important during early stages of learning, and that there is a shift to the cerebellar nuclei during later stages. As yet, human studies have provided little to resolve this question. In the present study, we established a setup that allows ultra-high-field 7T functional magnetic resonance imaging (fMRI) of the cerebellar cortex and interposed cerebellar nuclei simultaneously during delay eyeblink conditioning in humans. Event-related fMRI signals increased concomitantly in the cerebellar cortex and nuclei during early acquisition of conditioned eyeblink responses in 20 healthy human subjects. ANOVAs with repeated-measures showed significant effects of time across five blocks of 20 conditioning trials in the cortex and nuclei (p < 0.05, permutation corrected). Activations were most pronounced in, but not limited to, lobules VI and interposed nuclei. Increased activations were most prominent at the first time the maximum number of conditioned responses was achieved. Our data are consistent with a simultaneous and synergistic two-site model of learning during acquisition of classically conditioned eyeblinks. Because increased MRI signal reflects synaptic activity, concomitantly increased signals in the cerebellar nuclei and cortex are consistent with findings of learning related potentiation at the mossy fiber to nuclear cell synapse and mossy fiber to granule cell synapse. Activity related to the expression of conditioned responses, however, cannot be excluded.

eyeblink conditioning
fMRI
human
interposed nuclei
acquisition
cerebellum