Can Herbivore-Induced Volatiles Protect Plants by Increasing the Herbivores' Susceptibility to Natural Pathogens?

Abstract: In response to insect herbivory, plants mobilize various defenses. Defense responses include the release of herbivore-induced plant volatiles (HIPVs) that can serve as signals to alert undamaged tissues and to attract natural enemies of the herbivores. Some HIPVs can have a direct negative impact on herbivore survival, but it is not well understood by what mechanisms. Here, we tested the hypothesis that exposure to HIPVs renders insects more susceptible to natural pathogens. Exposure of the caterpillars of the noctuid Spodoptera exigua to indole and linalool, but not exposure to (Z)-3-hexenyl acetate, increased the susceptibility to Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV). We also found that exposure to indole, but not exposure to linalool or (Z)-3-hexenyl acetate, increased the pathogenicity of Bacillus thuringiensis Additional experiments revealed significant changes in microbiota composition after forty-eight hours of larval exposure to indole. Overall, these results provide evidence that certain HIPVs can strongly enhance the susceptibility of caterpillars to pathogens, possibly through effects on the insect gut microbiota. These findings suggest a novel mechanism by which HIPVs can protect plants from herbivorous insects.IMPORTANCE Multitrophic interactions involving insect pests, their natural enemies, microorganisms, and plant hosts are increasingly being recognized as relevant factors in pest management. In response to herbivory attacks, plants activate a wide range of defenses that aim to mitigate the damage. Attacked plants release herbivore-induced plant volatiles (HIPVs), which can act as priming signals for other plants and attract natural enemies of herbivores, and which may have a direct negative impact on herbivore survival. In the present work, we show that exposure of the insects to the induced volatiles could increase the insects' susceptibility to the entomopathogens naturally occurring in the plant environment. These findings suggest a novel role for plant volatiles by influencing insect interactions with natural pathogens, probably mediated by alterations in the insect microbiota composition. In addition, this work provides evidence for selectable plant traits (production of secondary metabolites) that can have an influence on the ecology of the pests and could be relevant in the improvement of pest management strategies using natural entomopathogens.

plant volatiles
indole
linalool
Bacillus thuringiensis
entomopathogen
baculovirus
plant-microbe interactions


Change in Mandibular Position in Patients With Syndromic Craniosynostosis After Midfacial Advancement With Distraction Osteogenesis.

Abstract:
OBJECTIVE
Characterize mandibular morphology in patients with syndromic craniosynostosis and document changes in mandibular position following midfacial advancement using distraction osteogenesis (DO).

DESIGN
Retrospective chart review and analysis of cephalometric radiographs.

SETTING
Tertiary care center.

PATIENTS
Patients with syndromic craniosynostosis who had midfacial advancement with DO at Boston Children's Hospital between 2000 and 2012. Mandibular morphology was characterized in 26 patients (15 boys and 11 girls) with a mean age of 11 years, 9 months. Pre- and postoperative analyses were performed for 17 (10 boys and 7 girls) of the 26 patients with a mean age of 11 years, 9 months.

MAIN OUTCOME MEASURES
Mandibular morphology and mandibular position. Data were compared to standard data from the Michigan Growth Study.

RESULTS
Comparison of preoperative mandibular measurements to standard data showed that patients with syndromic craniosynostosis have a shorter mandibular body and length and an obtuse gonial angle. Comparison of pre- and postoperative cephalograms showed that, following midfacial advancement with DO, the maxilla moved forward and the mandible moved backward and downward.

CONCLUSIONS
Patients with syndromic craniosynostosis have a smaller mandible length and obtuse gonial angle. Correction of midfacial hypoplasia with DO results in inferior and posterior mandibular movement. Clinicians can use this information to counsel patients regarding anticipated changes in facial profile and the need for adjunct procedures.

Ali|Naeem|N|
Brustowicz|Katherine|K|
Hosomura|Naoshi|N|
Bruun|Richard A|RA|
Padwa|Bonnie L|BL|

craniosynostosis
distraction osteogenesis
Le Fort osteotomy


Relationship between obesity and health-related quality of life in children aged 7-8 years.

Abstract:
BACKGROUND
The dramatic increase in the prevalence of obesity in developed and developing countries has become a major health care concern. Accordingly, there is growing recognition of the relationship between health-related quality of life (HRQOL) and obesity in the pediatric population. This study aimed to explore the relationship between HRQOL and different indicators of obesity in children aged 7-8 years.

METHOD
In total, 182 children participated in this study (mean age 7.71 (0.29) years, 48.91% girls). To assess obesity, an InBody 230 analyzer was used to calculate body mass index (BMI) and body fat percentage (BFP). The proxy version of the KIDSCREEN-27 questionnaire was used to assess HRQOL.

RESULTS
Among boys, 17.2% were overweight and 4.3% were obese according to BMI, while in terms of body fat percentage (BFP), the corresponding percentages were 12.9 and 9.7%, respectively. Among girls, the prevalence of overweight and obesity was 11.2 and 9.0% by BMI and 10.1 and 7.9% in terms of BFP, respectively. The analysis of BFP showed a significantly higher score in normal weight boys than in obese boys in the Social Support & Peers domains (KW H-test = 10.472, p = 0.03), while in girls, there were no significant differences between weight categories and any HRQOL dimensions.

CONCLUSION
Obesity at 7-8 years of age could negatively affect some HRQOL domains; in particular, obese boys may have low social support and peer functioning.


Alpha-Synuclein RNA Expression is Increased in Major Depression.

Abstract: Alpha-synuclein (SNCA) is a small membrane protein that plays an important role in neuro-psychiatric diseases. It is best known for its abnormal subcellular aggregation in Lewy bodies that serves as a hallmark of Parkinson's disease (PD). Due to the high comorbidity of PD with depression, we investigated the role of SNCA in patients suffering from major depressive disorder (MDD). SNCA mRNA expression levels were analyzed in peripheral blood cells of MDD patients and a healthy control group. SNCA mRNA expression was positively correlated with severity of depression as indicated by psychometric assessment. We found a significant increase in SNCA mRNA expression levels in severely depressed patients compared with controls. Thus, SNCA analysis could be a helpful target in the search for biomarkers of MDD.

alpha-synuclein
major depression
SNCA
Hamilton Scale of Depression


The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations.

Abstract: The field of human therapeutics has expanded tremendously from small molecules to complex biological modalities, and this trend has accelerated in the last two decades with a greater diversity in the types and applications of novel modalities, accompanied by increasing sophistication in drug delivery technology. These innovations have led to a corresponding increase in the number of therapies seeking regulatory approval, and as the industry continues to evolve regulations will need to adapt to the ever-changing landscape. The growth in this field thus represents a challenge for regulatory authorities as well as for sponsors. This review provides a brief description of novel biologics, including innovative antibody therapeutics, genetic modification technologies, new developments in vaccines, and multifunctional modalities. It also describes a few pertinent drug delivery mechanisms such as nanoparticles, liposomes, coformulation, recombinant human hyaluronidase for subcutaneous delivery, pulmonary delivery, and 3D printing. In addition, it provides an overview of the current CMC regulatory challenges and discusses potential methods of accelerating regulatory mechanisms for more efficient approvals. Finally, we look at the future of biotherapeutics and emphasize the need to bring these modalities to the forefront of patient care from a global perspective as effectively as possible.

Gutierrez|Lucas|L|
Cauchon|Nina S|NS|
Christian|Twinkle R|TR|
Giffin|Michael J|MJ|
Abernathy|Michael J|MJ|

Vaccines
Liposome
Antibody drug(s)
Automation
Drug design
Gene therapy
Immunotherapy
Nanoparticle(s)
Regulatory science
Targeted drug delivery


The Dual Role of HLA-C in Tolerance and Immunity at the Maternal-Fetal Interface.

Abstract: To establish a healthy pregnancy, maternal immune cells must tolerate fetal allo-antigens and remain competent to respond to infections both systemically and in placental tissues. Extravillous trophoblasts (EVT) are the most invasive cells of extra-embryonic origin to invade uterine tissues and express polymorphic Human Leucocyte Antigen-C (HLA-C) of both maternal and paternal origin. Thus, HLA-C is a key molecule that can elicit allogeneic immune responses by maternal T and NK cells and for which maternal-fetal immune tolerance needs to be established. HLA-C is also the only classical MHC molecule expressed by EVT that can present a wide variety of peptides to maternal memory T cells and establish protective immunity. The expression of paternal HLA-C by EVT provides a target for maternal NK and T cells, whereas HLA-C expression levels may influence how this response is shaped. This dual function of HLA-C requires tight transcriptional regulation of its expression to balance induction of tolerance and immunity. Here, we critically review new insights into: (i) the mechanisms controlling expression of HLA-C by EVT, (ii) the mechanisms by which decidual NK cells, effector T cells and regulatory T cells recognize HLA-C allo-antigens, and (iii) immune recognition of pathogen derived antigens in context of HLA-C.

Papúchová|Henrieta|H|
Meissner|Torsten B|TB|
Li|Qin|Q|
Strominger|Jack L|JL|
Tilburgs|Tamara|T|

pregnancy
trophoblast
human
decidual NK cells
effector T cells
regulatory T cells
HLA-G
decidua


Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers.

Abstract: Esophageal cancer (EC) represents a human malignancy, diagnosed often at the advanced stage of cancer and resulting in high morbidity and mortality. The development of precision medicine allows for the identification of more personalized therapeutic strategies to improve cancer treatment. By implanting primary cancer tissues into immunodeficient mice for expansion, patient-derived xenograft (PDX) models largely maintain similar histological and genetic representations naturally found in patients' tumor cells. PDX models of EC (EC-PDX) provide fine platforms to investigate the tumor microenvironment, tumor genomic heterogeneity, and tumor response to chemoradiotherapy, which are necessary for new drug discovery to combat EC in addition to optimization of current therapeutic strategies for EC. In this review, we summarize the methods used for establishing EC-PDX models and investigate the utilities of EC-PDX in screening predictive biomarkers and potential therapeutic targets. The challenge of this promising research tool is also discussed.

Lan|Tianfeng|T|
Xue|Xia|X|
Dunmall|Louisa Chard|LC|
Miao|Jinxin|J|
Wang|Yaohe|Y|

D023041:Xenograft Model Antitumor Assays

patient-derived xenograft
biomarkers
therapeutic targets
esophageal cancer
immunodeficient mice


Physicochemical properties of iron oxide nanoparticles that contribute to cellular ROS-dependent signaling and acellular production of hydroxyl radical.

Abstract: While nanoparticles (NPs) are increasingly used in a variety of consumer products and medical applications, some of these materials have potential health concerns. Macrophages are the primary responders to particles that initiate oxidative stress and inflammatory reactions. Here, we utilized six flame-synthesized, engineered iron oxide NPs with various physicochemical properties (e.g. Fe oxidation state and crystal size) to study their interactions with RAW 264.7 macrophages, their iron solubilities, and their abilities to produce hydroxyl radical in an acellular assay. Both iron solubility and hydroxyl radical production varied between NPs depending on crystalline diameter and surface area of the particles, but not on iron oxidation state. Macrophage treatment with the iron oxide NPs showed a dose-dependent increase of heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase (NQO-1). The nuclear factor (NF)-erythroid-derived 2 (E2)-related factor 2 (Nrf2) modulates the transcriptional activity of antioxidant response element (ARE)-driven genes, such as HO-1 and NQO-1. Here, we show that the iron oxide NPs activate Nrf2, leading to its increased nuclear accumulation and enhanced Nrf2 DNA-binding activity in NP-treated RAW 264.7 macrophages. Iron solubility and acellular hydroxyl radical generation depend on the physical properties of the NPs, especially crystalline diameter; however, these properties are weakly linked to the activation of cellular signaling of Nrf2 and the expression of oxidative stress markers. Overall, our work shows for the first time that iron oxide nanoparticles induce cellular marker genes of oxidative stress and that this effect is transcriptionally mediated through the Nrf2-ARE signaling pathway in macrophages.

Vogel|Christoph F A|CF|
Charrier|Jessica G|JG|
Wu|Dalei|D|
McFall|Alexander S|AS|
Li|Wen|W|
Abid|Aamir|A|
Kennedy|Ian M|IM|
Anastasio|Cort|C|

D002470:Cell Survival
D005290:Ferric Compounds
D017665:Hydroxyl Radical
D008264:Macrophages
D053758:Nanoparticles
D018384:Oxidative Stress
D017382:Reactive Oxygen Species
D015398:Signal Transduction
D014162:Transfection

nanoparticles
Hydroxyl radical
macrophage
oxidative stress
Nrf2


Medicinal chemistry insights in the discovery of novel LSD1 inhibitors.

Abstract: LSD1 is an epigenetic modulator associated with transcriptional regulation of genes involved in a broad spectrum of key cellular processes, and its activity is often altered under pathological conditions. LSD1 inhibitors are considered to be candidates for therapy of cancer, viral diseases and neurodegeneration. Many LSD1 inhibitors with various scaffolds have been disclosed, and a few potent molecules are in different stages of clinical development. In this review, we summarize recent biological findings on the roles of LSD1 and the current understanding of the clinical significance of LSD1, and focus on the medicinal chemistry strategies used in the design and development of LSD1 inhibitors as drug-like epigenetic modulators since 2012, including a brief consideration of structure-activity relationships.

Wang|Xueshun|X| Huang|Boshi|B| Suzuki|Takayoshi|T| Liu|Xinyong|X| Zhan|Peng|P|

D000818:Animals
D002626:Chemistry, Pharmaceutical
D055808:Drug Discovery
D004791:Enzyme Inhibitors
D044127:Epigenesis, Genetic
D056466:Histone Demethylases
D006801:Humans
D013329:Structure-Activity Relationship

medicinal chemistry
LSD1
drug design
epigenomics
histone modification


Using network clustering to predict copy number variations associated with health disparities.

Abstract: Substantial health disparities exist between African Americans and Caucasians in the United States. Copy number variations (CNVs) are one form of human genetic variations that have been linked with complex diseases and often occur at different frequencies among African Americans and Caucasian populations. Here, we aimed to investigate whether CNVs with differential frequencies can contribute to health disparities from the perspective of gene networks. We inferred network clusters from human gene/protein networks based on two different data sources. We then evaluated each network cluster for the occurrences of known pathogenic genes and genes located in CNVs with different population frequencies, and used false discovery rates to rank network clusters. This approach let us identify five clusters enriched with known pathogenic genes and with genes located in CNVs with different frequencies between African Americans and Caucasians. These clustering patterns predict two candidate causal genes located in four population-specific CNVs that play potential roles in health disparities.

Clustering
Health disparities
Copy Number Variations (CNVs)
Gene networks
Gene Ontology
Gene-disease association


Autonomic Nervous System Correlates of Speech Categorization Revealed Through Pupillometry.

Abstract: Human perception requires the many-to-one mapping between continuous sensory elements and discrete categorical representations. This grouping operation underlies the phenomenon of categorical perception (CP)-the experience of perceiving discrete categories rather than gradual variations in signal input. Speech perception requires CP because acoustic cues do not share constant relations with perceptual-phonetic representations. Beyond facilitating perception of unmasked speech, we reasoned CP might also aid the extraction of target speech percepts from interfering sound sources (i.e., noise) by generating additional perceptual constancy and reducing listening effort. Specifically, we investigated how noise interference impacts cognitive load and perceptual identification of unambiguous (i.e., categorical) vs. ambiguous stimuli. Listeners classified a speech vowel continuum (/u/-/a/) at various signal-to-noise ratios (SNRs [unmasked, 0 and -5 dB]). Continuous recordings of pupil dilation measured processing effort, with larger, later dilations reflecting increased listening demand. Critical comparisons were between time-locked changes in eye data in response to unambiguous (i.e., continuum endpoints) tokens vs. ambiguous tokens (i.e., continuum midpoint). Unmasked speech elicited faster responses and sharper psychometric functions, which steadily declined in noise. Noise increased pupil dilation across stimulus conditions, but not straightforwardly. Noise-masked speech modulated peak pupil size (i.e., [0 and -5 dB] > unmasked). In contrast, peak dilation latency varied with both token and SNR. Interestingly, categorical tokens elicited earlier pupil dilation relative to ambiguous tokens. Our pupillary data suggest CP reconstructs auditory percepts under challenging listening conditions through interactions between stimulus salience and listeners' internalized effort and/or arousal.

Lewis|Gwyneth A|GA|
Bidelman|Gavin M|GM|

pupillometry
categorical perception
listening effort
eye behavior
speech-in-noise (SIN) perception


PGC-1α and ERRα in patients with endometrial cancer: a translational study for predicting myometrial invasion.

Abstract:
BACKGROUND
PGC-1α and ERRα are closely related to tumor formation and progression. However, the mechanism underlying the involvement of PGC-1α/ERRα in regulating invasion and migration in endometrial cancer remains to be explored.

RESULTS
Elevated levels of PGC-1α and ERRα were associated with advanced myometrial invasion, and PGC-1α and Vimentin expression was related to the depth of myometrial invasion in premenopausal endometrial cancer. Silencing of PGC-1α reduced ERRα activation and inhibited epithelial-mesenchymal-transition phenotypes, resulting in significant inhibition of invasion and migration. Overexpression of ERRα led to enhanced PGC-1α expression and increased activity of TFEB, promoting epithelial-mesenchymal-transition in endometrial cancer cells.

CONCLUSIONS
PGC-1α and ERRα induce the epithelial-mesenchymal-transition therefore invasion and migration in endometrial cancer, and may be novel biomarkers to predict the risk of advanced myometrial invasion.

METHODS
PGC-1α, ERRα, and vimentin expression was analyzed in tissue microarrays using immunohistochemistry. PGC-1α and ERRα expression in endometrial cancer cell lines was investigated using quantitative PCR and western blotting analyses after infection with lentivirus-mediated small interfering RNA (siRNA) targeting PGC-1α (siRNA-PGC-1α) or overexpressing ERRα. E-cadherin and vimentin levels were determined using western blotting and cell immunouorescence analyses. Cell migration and invasiveness were evaluated using scratch and trans-well chamber assays.

Chen|LiLi|L| Mao|XiaoDan|X| Huang|MeiMei|M| Lei|HuiFang|H| Xue|LiFang|L| Sun|PengMing|P|

PGC-1α
ERRα
endometrial cancer
invasion
epithelial-mesenchymal-transition


Targeting the Non-catalytic RVxF Site of Protein Phosphatase-1 With Small Molecules for Ebola Virus Inhibition.

Abstract: Ebola virus (EBOV) is a non-segmented negative-sense RNA virus that causes a severe human disease. The ongoing EBOV outbreak in the Eastern part of Democratic Republic of the Congo has resulted to date in over 2500 confirmed cases including over 1500 deaths. Difficulties with vaccine administration indicate the necessity for development of new general drugs and therapeutic strategies against EBOV. Host Ser/Thr protein phosphatases, particularly PP1 and PP2A, facilitate EBOV transcription by dephosphorylating the EBOV VP30 protein and switching activity of the polymerase complex toward replication. Previously, we developed small molecule 1E7-03 that targeted host protein phosphatase-1 (PP1) and induces phosphorylation of EBOV VP30 protein thus shifting transcription-replication balance and inhibiting EBOV replication. Here, we developed a new EBOV inhibitor, 1E7-07, that potently inhibits EBOV replication and displays significantly improved metabolic stability when compared to previously described 1E7-03. Proteome analysis of VP30 shows that 1E7-07 increases its phosphorylation on Thr-119 and Ser-124 over 3-fold with p < 0.001, which likely contributes to EBOV inhibition. We analyzed 1E7-07 binding to PP1 using a mass spectrometry-based protein painting approach. Combined with computational docking, protein painting shows that 1E7-07 binds to several PP1 sites including the RVxF site, C-terminal groove and NIPP1-helix binding pocket. Further analysis using surface plasmon resonance and a split NanoBiT system demonstrates that 1E7-07 binds primarily to the RVxF site. Together, detailed analysis of 1E7-07 binding to PP1 and identification of the RVxF site as the main binding site opens up an opportunity for future development of PP1-targeting EBOV inhibitors.

Lin|Xionghao|X|
Ammosova|Tatiana|T|
Choy|Meng S|MS|
Pietzsch|Colette A|CA|
Ivanov|Andrey|A|
Ahmad|Asrar|A|
Saygideğer|Yasemin|Y|
Kumari|Namita|N|
Kovalskyy|Dmytro|D|
Üren|Aykut|A|
Peti|Wolfgang|W|
Bukreyev|Alexander|A|
Nekhai|Sergei|S|

protein phosphatase-1
Ebola virus
protein painting
surface plasmon resonance
split NanoBiT
mass spectrometry
small molecule EBOV inhibitor


In situ 13CO2 pulse labelling of field-grown eucalypt trees revealed the effects of potassium nutrition and throughfall exclusion on phloem transport of photosynthetic carbon.

Abstract: Potassium (K) is an important limiting factor of tree growth, but little is known of the effects of K supply on the long-distance transport of photosynthetic carbon (C) in the phloem and of the interaction between K fertilization and drought. We pulse-labelled 2-year-old Eucalyptus grandis L. trees grown in a field trial combining K fertilization (+K and -K) and throughfall exclusion (+W and -W), and we estimated the velocity of C transfer by comparing time lags between the uptake of (13)CO2 and its recovery in trunk CO2 efflux recorded at different heights. We also analysed the dynamics of the labelled photosynthates recovered in the foliage and in the phloem sap (inner bark extract). The mean residence time of labelled C in the foliage was short (21-31 h). The time series of (13)C in excess in the foliage was affected by the level of fertilization, whereas the effect of throughfall exclusion was not significant. The velocity of C transfer in the trunk (0.20-0.82 m h(-1)) was twice as high in +K trees than in -K trees, with no significant effect of throughfall exclusion except for one +K -W tree labelled in the middle of the drought season that was exposed to a more pronounced water stress (midday leaf water potential of -2.2 MPa). Our results suggest that besides reductions in photosynthetic C supply and in C demand by sink organs, the lower velocity under K deficiency is due to a lower cross-sectional area of the sieve tubes, whereas an increase in phloem sap viscosity is more likely limiting phloem transport under drought. In all treatments, 10 times less (13)C was recovered in inner bark extracts at the bottom of the trunk when compared with the base of the crown, suggesting that a large part of the labelled assimilates has been exported out of the phloem and replaced by unlabelled C. This supports the 'leakage-retrieval mechanism' that may play a role in maintaining the pressure gradient between source and sink organs required to sustain high velocity of phloem transport in tall trees.

Epron|Daniel|D|
Cabral|Osvaldo Machado Rodrigues|OM|
Laclau|Jean-Paul|JP|
Dannoura|Masako|M|
Packer|Ana Paula|AP|
Plain|Caroline|C|
Battie-Laclau|Patricia|P|
Moreira|Marcelo Zacharias|MZ|
Trivelin|Paulo Cesar Ocheuze|PC|
Bouillet|Jean-Pierre|JP|
Gérant|Dominique|D|
Nouvellon|Yann|Y|

fertilization
drought
Eucalyptus grandis
carbon isotope
carbon transfer


The EDIC Method: An Engaging and Comprehensive Approach for Creating Health Department Workforce Development Plans.

Abstract: In 2013, the Nebraska Department of Health & Human Services, Division of Public Health (Nebraska's State Health Department); and the University of Nebraska Medical Center, College of Public Health developed a comprehensive approach to assess workforce training needs. This article outlines the method used to assess the education and training needs of Division staff, and develop comprehensive workforce development plans to address those needs. The EDIC method (Engage, Develop, Identify, and Create) includes the following four phases: (1) Engage Stakeholders, (2) Develop Assessment, (3) Identify Training Needs, and (4) Create Development Plans. The EDIC method provided a process grounded in science and practice, allowed input, and produced buy-in from staff at all levels throughout the Division of Public Health. This type of process provides greater assurance that the most important gaps in skills and competencies will be identified. Although it is a comprehensive approach, it can be replicated at the state or local level across the country.

Grimm|Brandon L|BL|
Brandert|Kathleen|K|
Palm|David|D|
Svoboda|Colleen|C|

D006077:Government Agencies
D006282:Health Personnel
D006801:Humans
D011361:Professional Competence
D013192:Staff Development
D013219:State Government


Urgent Inpatient Colectomy Carries a Higher Morbidity and Mortality than Elective Surgery.

Abstract:
BACKGROUND
Emergency colorectal surgery confers a higher risk of adverse outcomes compared to elective surgery. Few studies have examined the outcomes after urgent colectomies, typically defined as those performed at the index admission, but not performed at admission in an emergency fashion. The aim of this study is to evaluate the risk of adverse outcomes following urgent inpatient colorectal surgery.

MATERIALS AND METHODS
All adult patients undergoing colectomy between 2013 and 2017 in the ACS NSQIP were included in the analysis. Patients were grouped into Elective, Urgent and Emergency groups. The Urgent group was further stratified by time from admission to surgery. Baseline characteristics and 30 day outcomes were compared between the Elective, Urgent and Emergency groups using univariable and multivariable analyses.

RESULTS
104,486 patients underwent elective colorectal resection. 23,179 underwent urgent while 22,241 had emergency resections. Patients undergoing urgent colectomy presented with increased comorbidities, and experienced higher mortality (2.5-4.1%, AOR 2.3 (1.9 - 2.8)) compared to elective surgery (0.4%). Urgent colectomy was an independent risk factor for the majority of short term complications documented in NSQIP. Moreover, patients undergoing urgent colectomy more than a week following admission had an increased risk of bleeding, deep venous thrombosis, pulmonary embolism, urinary tract infection, and prolonged hospitalization.

CONCLUSION
Urgent colectomies are associated with a greater risk of adverse outcomes compared to elective surgery. Urgent status is an independent risk factor for post operative mortality and morbidity. Further characterization of this patient population and their specific challenges may help ameliorate these adverse events.

Hajirawala|Luv|L| Leonardi|Claudia|C| Orangio|Guy|G| Davis|Kurt|K| Barton|Jeffrey|J|

Urgent
Colectomy
Morbidity
Mortality
Elective
Emergent
Colorectal Surgery


Choosing the right metal: case studies of class I ribonucleotide reductases.

Abstract: Over one-third of all proteins require metallation for function (Waldron, K. J., Rutherford, J. C., Ford, D., and Robinson, N.J. (2009) Nature 460, 823-830). As biochemical studies of most proteins depend on their isolation subsequent to recombinant expression (i.e. they are seldom purified from their host organism), there is no gold standard to assess faithful metallocofactor assembly and associated function. The biosynthetic machinery for metallocofactor formation in the recombinant expression system may be absent, inadequately expressed, or incompatible with a heterologously expressed protein. A combination of biochemical and genetic studies has led to the identification of key proteins involved in biosynthesis and likely repair of the metallocofactor of ribonucleotide reductases in both bacteria and the budding yeast. In this minireview, we will discuss the recent progress in understanding controlled delivery of metal, oxidants, and reducing equivalents for cofactor assembly in ribonucleotide reductases and highlight issues associated with controlling Fe/Mn metallation and avoidance of mismetallation.

Huang|Mingxia|M|
Parker|Mackenzie J|MJ|
Stubbe|JoAnne|J|

Metallation
Ribonucleotide Reductase
Yeast
Mismetallation
Bacterial Pathogenesis
Iron
Iron-Sulfur Protein
Manganese
Metal Homeostasis


Efficacy of favipiravir (T-705) against Crimean-Congo hemorrhagic fever virus infection in cynomolgus macaques.

Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is a widely distributed hemorrhagic fever virus found throughout Eastern Europe, Africa, the Middle East and Asia. It is spread through bites from infected ticks, animal husbandry and can also be acquired in the healthcare setting during care of infected patients. In humans, CCHFV can cause a sudden onset of a non-specific febrile illness that can rapidly progress to severe hemorrhagic manifestations. Currently, there is no widely available vaccine and although ribavirin has been suggested for the treatment of CCHFV, clinical efficacy in both animal models and humans is inconsistent suggesting more potent antivirals are needed for CCHFV. Favipiravir is approved in Japan for the treatment of influenza virus infections and has shown promise against other highly pathogenic RNA viruses including CCHFV with demonstrated efficacy in the type I interferon deficient mouse model. In this report we utilized the cynomolgus macaque model to evaluate the efficacy of once- and twice-daily favipiravir treatment against CCHFV infection. We found that favipiravir treatment suppressed viremia and viral shedding when treatment was initiated 24 h post-infection and viral burdens in key tissues trended lower in favipiravir-treated animals. Our data indicate that favipiravir has efficacy against CCHFV in vivo in a non-human primate model of infection.

Hawman|David W|DW|
Haddock|Elaine|E|
Meade-White|Kimberly|K|
Nardone|Glenn|G|
Feldmann|Friederike|F|
Hanley|Patrick W|PW|
Lovaglio|Jamie|J|
Scott|Dana|D|
Komeno|Takashi|T|
Nakajima|Nozomi|N|
Furuta|Yousuke|Y|
Gowen|Brian B|BB|
Feldmann|Heinz|H|

D003225:Hemorrhagic Fever Virus, Crimean-Congo

Favipiravir
Crimean-Congo hemorrhagic Fever
Macaques
Antiviral


Invasive aspergillosis among heart transplant recipients: a 24-year perspective.

Abstract:
BACKGROUND
Invasive aspergillosis is a well-known complication in severely immunosuppressed patients, including heart transplant recipients, and associated mortality is high. Despite the severity of the disease in this population, few recent series with secular trends have addressed the problem.

METHODS
We performed a descriptive study of 479 consecutive heart transplant recipients from 1988 to 2011 in a single institution.

RESULTS
Overall invasive aspergillosis incidence in heart transplant recipients was 6.5% (31 of 479). Incidence decreased from 8.7% (24 of 277) in the period 1988 to 2000 (historical cohort) to 3.5% (7 of 202) afterward (p = 0.02); 4 of the 7 cases were in the context of an outbreak. The most common presentation was lung infection, but episodes occurring >3 months after transplantation (late aspergillosis) showed a higher frequency of disseminated disease and involvement of the central nervous system and of atypical sites compared with early (first 3 months) episodes. Related mortality was 36%, with a significant decrease between the historical cohort and the present cohort: 46% vs 0% (p = 0.04) and a trend toward lower related death in early vs late cases (26% vs 63%, p = 0.09).

CONCLUSIONS
In our series, both incidence and mortality associated with invasive aspergillosis in heart transplant recipients showed a decrease in recent years. Careful environmental management and targeted anti-fungal prophylaxis may minimize the incidence of invasive aspergillosis in this setting.

Muñoz|Patricia|P| Cerón|Ines|I| Valerio|Maricela|M| Palomo|Jesús|J| Villa|Adolfo|A| Eworo|Alia|A| Fernández-Yáñez|Juan|J| Guinea|Jesús|J| Bouza|Emilio|E|

invasive aspergillosis
heart transplantation
anti-fungal prophylaxis
Aspergillus spp


Fertility traits of purebred Holsteins and 2- and 3-breed crossbred heifers and cows obtained from Swedish Red, Montbéliarde, and Brown Swiss sires.

Abstract: The objective of this study was to compare fertility traits of heifers and primiparous cows from Swedish Red × Holstein (SR × HO; n=634 and 581, respectively), Montbéliarde × Holstein (MO × HO; n=126 and 114, respectively), Brown Swiss × Holstein (BS × HO; n=59 and 50, respectively), and MO × (SR × HO) (n=241 and 139, respectively) crossbreds, versus those of Holstein heifers and cows (HO; n=3,483 and 2,549, respectively). Animals were born between 2007 and 2011, and belonged to 4 herds located in northern Italy. Heifers were compared for age at first service (AFS), age at first conception (AFC), interval between first service and conception (IFC), nonreturn rate at 56 d after first service (NR56), conception rate at first service (CR), and number of inseminations required for conception (INS). The same traits were evaluated in primiparous cows, except that AFS and AFC were replaced with days at first service (DFS) and days open (DO). The AFS, AFC, IFC, DFS, and DO traits were continuous variables and were thus analyzed under a proportional hazards Cox model that properly accounted for censoring among cows that were culled or failed to conceive. The NR56, CR, and INS traits were analyzed as binary traits using logistic regression. Our results indicated that, among heifers, SR × HO crossbreds had a better chance of having an earlier first service and conceiving earlier than HO, with hazard ratios (HR) of 1.31 for AFS and 1.34 for AFC. Similarly, MO × (SR × HO) crossbreds differed from HO heifers in this regard (HR=1.18 and 1.24, respectively). For the primiparous cows, all crossbreds showed significant differences for DFS, DO, and IFC relative to purebred HO, with the exception of the BS × HO crossbreds. The MO × HO, SR × HO, and MO × (SR × HO) crossbred cows showed increased chances of having fewer DFS (HR=1.40, 1.30, and 1.27, respectively), fewer DO (HR=1.59, 1.43, and 1.58, respectively), and fewer IFC (HR=1.52, 1.26, and 1.39, respectively) than HO cows. All crossbred genotypes, including BS × HO cows, showed higher probabilities for higher NR56, higher CR, and lower INS than purebred HO cows. Together, these findings indicate that the studied crossbred cows have higher reproductive potential than Holsteins.

fertility
Swedish Red
Montbéliarde
crossbreeding
survival analysis


Surrogate Endpoints in Oncology: Overview of Systematic Reviews and Their Use for Health Decision Making in Mexico.

Abstract:
OBJECTIVES
The use of surrogate endpoints (SEs) for cancer drug approval in health systems is common. The objectives of this study were to identify systematic reviews (SRs) that evaluated the correlation of SEs with overall survival (OS) in cancer drugs to analyze the applications of approved cancer drugs with SEs in Mexico and to apply the validation framework proposed by the Institute for Quality and Efficiency in Health Care (IQWiG).

METHODS
An overview of SRs was conducted according to Cochrane Collaboration methodology. Applications for approved cancer drugs with SEs in Mexico were analyzed. The IQWiG validation framework was applied to evaluate the SEs identified in the overview and in the applications in Mexico.

RESULTS
A total of 85 SRs that assessed 192 SEs for different types of cancer were selected. According to the IQWiG model, only 2.5% of the SEs analyzed in the overview and only one of the applications in Mexico could be used as surrogates for OS because the reliability (methodological quality) of the SRs and the strength of the correlation of SEs with OS was mostly low (92%) and low (correlation coefficient r ≤ 0.7; 50.5%), respectively. Of the total number of cancer drugs approved in Mexico, 19.4% used SEs.

CONCLUSIONS
Most SEs for different types of cancer could not be used as surrogates for OS according to the IQWiG model, and their use for the approval of cancer drugs in Mexico is generally not justified.

Ortiz|Yesenia|Y|
Fareli|Christian J|CJ|
Gallegos|Veronica|V|
Hernández|Esteban|E|

surrogate endpoints
health decision making
validation framework
antineoplastic agents
overview of reviews
patient-relevant endpoints


On model specification and selection of the Cox proportional hazards model.

Abstract: Prognosis plays a pivotal role in patient management and trial design. A useful prognostic model should correctly identify important risk factors and estimate their effects. In this article, we discuss several challenges in selecting prognostic factors and estimating their effects using the Cox proportional hazards model. Although a flexible semiparametric form, the Cox's model is not entirely exempt from model misspecification. To minimize possible misspecification, instead of imposing traditional linear assumption, flexible modeling techniques have been proposed to accommodate the nonlinear effect. We first review several existing nonparametric estimation and selection procedures and then present a numerical study to compare the performance between parametric and nonparametric procedures. We demonstrate the impact of model misspecification on variable selection and model prediction using a simulation study and an example from a phase III trial in prostate cancer.

D017326:Clinical Trials, Phase III as Topic

COSSO
Cox model
LASSO
model selection
smoothing splines


Effect of Starch Source in Pelleted Concentrates on Fecal Bacteria in Prepartum and Postpartum Mares.

Abstract: Dietary starch source has been shown to affect fecal bacterial communities of horses fed minimally processed cereal grains. However, processing may increase foregut starch digestibility, reducing effects of starch source on fecal bacterial communities. This study aimed to determine the effect of starch source in pelleted concentrates on fecal Lactobacillus spp., amylolytic bacteria, and cellulolytic bacteria in broodmares mares, during the prepartum and postpartum period. Thoroughbred mares (n = 18) were paired by last breeding date then randomly assigned to either an oat-based or a corn and wheat middlings-based pelleted concentrate fed with forage. Mares were fed their assigned concentrates beginning on 310 days of gestation, and fecal samples were collected at 324 days of gestation, before parturition, 1 day, 14 days, and 28 days postpartum. Fecal samples were enumerated by serial dilution and inoculation into selective, enriched media for Lactobacillus spp., amylolytic bacteria, and cellulolytic bacteria. Data were log transformed then analyzed using a mixed model ANOVA with repeated measures (SAS 9.3) to test the main effects of treatment, time of sample, and treatment by time interaction. Starch source did not affect enumerated bacterial communities (P > .05); thus, pelleting concentrates may alter some of the effects of starch sources on the hindgut microbiota. Sample date did not affect amylolytic bacteria (P > .05); however, lactobacilli and cellulolytic bacteria decreased 1 day postpartum (P < .05). Although we did not observe an effect of starch source on fecal bacteria in mares, parturition did appear to alter the hindgut microbiota.

Pyles|Morgan B|MB|
Fowler|Ashley L|AL|
Bill|Veronica T|VT|
Crum|Andrea D|AD|
Hayes|Susan H|SH|
Harlow|Brittany E|BE|
Flythe|Michael D|MD|
Lawrence|Laurie M|LM|

Horse
Cereal grains
Parturition
Microbiota


Knowledge attitude and practice toward pertussis vaccination during pregnancy among pregnant and postpartum Italian women.

Abstract: In Italy, no specific recommendation toward maternal pertussis immunization during pregnancy has been issued. However, vaccination during pregnancy will be likely integrated in the Italian immunization program in the future. In order to identify barriers to achieving a sufficient vaccination coverage during pregnancy, we investigated knowledge, attitude and practice toward pertussis vaccination during pregnancy through a web-based survey. A total of 343 Italian pregnant women (N = 164) and women in the postpartum period (N = 183) completed the online questionnaire. More than a half of the study population was uncertain regarding the benefits of the vaccination during pregnancy. Only 1.7% of women in the postpartum had received the vaccination during pregnancy, and 21% of pregnant women declared the intention to be vaccinated in pregnancy. Only 34% would accept the vaccination in the current or in a future pregnancy, if recommended by a physician, and a half would remain uncertain. Perceiving the vaccine as harmful for the fetus' development is associated to a decreased willingness to be vaccinated if recommended by a HCP, both in pregnant women (OR 0.25 p = 0.010 95% CI 0.09-0.72) and in women in the postpartum period (OR 0.32 p =  0.006 95% CI 0.15-0.72). Our study suggests that the vaccination recommendation by physicians might not be sufficient to adequately raise vaccination coverage against pertussis among Italian pregnant women. A combination of educational interventions and tailored communi-cation campaigns could be implemented to promote maternal immunization.

Agricola|Eleonora|E|
Gesualdo|Francesco|F|
Alimenti|Lia|L|
Pandolfi|Elisabetta|E|
Carloni|Emanuela|E|
D'Ambrosio|Angelo|A|
Russo|Luisa|L|
Campagna|Ilaria|I|
Ferretti|Beatrice|B|
Tozzi|Alberto E|AE|

D007722:Health Knowledge, Attitudes, Practice

D010342:Patient Acceptance of Health Care


Hypercapnia Accelerates Adipogenesis: A Novel Role of High CO2 in Exacerbating Obesity.

Abstract: Obesity is a major risk factor for the development of obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS), which manifest as intermittent hypercapnia and sustained plus intermittent hypercapnia, respectively. In this study, we investigated whether CO2 affects adipocyte differentiation (adipogenesis) and maturation (hypertrophy). Human visceral or subcutaneous preadipocytes were grown to confluence and then induced to differentiate to adipocytes under hypocapnia, normocapnia, and hypercapnia with or without hypoxia. Adipogenesis was also induced under intermittent or sustained hypercapnia. Differentiated adipocytes were maintained to maturity under normocapnia or hypercapnia. Our main findings are as follows: (1) hypercapnia accelerated adipogenesis in visceral and subcutaneous preadipocytes, whereas hypocapnia inhibited adipogenesis; (2) hypercapnia did not affect adipocyte hypertrophy; (3) hypercapnia-accelerated adipogenesis was independent of extracellular acidosis, oxygen concentration, or either intermittent or sustained exposure to high CO2; and (4) the mechanisms underlying hypercapnia-accelerated adipogenesis involved increased production of cyclic adenosine monophosphate (cAMP) via soluble adenylyl cyclase, leading to the activation of protein kinase A and exchanger protein directly activated by cAMP, which, in turn, activated proadipogenic transcription factors, such as cAMP response element binding protein, CCAAT/enhancer binding protein β, and peroxisome proliferator-activated receptor γ. This study reveals a novel role of high CO2 in promoting adipogenesis, which provides mechanistic clues to a pathoetiological interaction between OSA/OHS and obesity. Our data suggest a vicious cycle of disease progression via the following mechanism: OSA/OHS → hypoventilation → hypercapnia → increased adipogenesis → increased fat mass → exacerbated OSA/OHS.

Kikuchi|Ryota|R| Tsuji|Takao|T| Watanabe|Osamu|O| Yamaguchi|Kazuhiro|K| Furukawa|Kinya|K| Nakamura|Hiroyuki|H| Aoshiba|Kazutetsu|K|

obesity
adipocytes
adipose tissue
respiratory insufficiency
sleep apnea syndrome


Coming of age? Women's sexual and reproductive health after twenty-one years of democracy in South Africa.

Abstract: This paper is a sequel to a 2004 article that reviewed South Africa's introduction of new sexual and reproductive health (SRH) and rights laws, policies and programmes, a decade into democracy. Similarly to the previous article, this paper focuses on key areas of women's SRH: contraception and fertility, abortion, maternal health, HIV, cervical and breast cancer and sexual violence. In the last decade, South Africa has retained and expanded its sexual and reproductive health and rights (SRHR) policies in the areas of abortion, contraception, youth and HIV treatment (with the largest antiretroviral treatment programme in the world). These are positive examples within the SRHR policy arena. These improvements include fewer unsafe abortions, AIDS deaths and vertical HIV transmission, as well as the public provision of a human papillomavirus vaccine to prevent cervical cancer. However, persistent socio-economic inequities and gender inequality continue to profoundly affect South African women's SRHR. The state shows mixed success over the past two decades in advancing measurable SRH social justice outcomes, and in confronting and ameliorating social norms that undermine SRHR.

Cooper|Diane|D| Harries|Jane|J| Moodley|Jennifer|J| Constant|Deborah|D| Hodes|Rebecca|R| Mathews|Cathy|C| Morroni|Chelsea|C| Hoffman|Margaret|M|

D000028:Abortion, Induced
D044966:Anti-Retroviral Agents
D001943:Breast Neoplasms
D003267:Contraception
D005260:Female
D015658:HIV Infections
D006291:Health Policy
D054625:Healthcare Disparities
D006801:Humans
D008427:Maternal Health Services
D011247:Pregnancy
D060728:Reproductive Health
D046269:Reproductive Rights
D012742:Sex Offenses
D012935:Social Justice
D013019:South Africa
D002583:Uterine Cervical Neoplasms
D016387:Women's Health
D014933:Women's Rights

women's sexual and reproductive health and rights


High content analysis assay for prediction of human hepatotoxicity in HepaRG and HepG2 cells.

Abstract: Drug-induced liver injury (DILI) results in the termination of drug development or withdrawal of a drug from the market. The establishment of a predictive, high-throughput preclinical test system to evaluate potential clinical DILI is therefore required. Here, we established a high content analysis (HCA) assay in human hepatocyte cell lines such as the HepaRG with normal expression levels of CYP enzymes and HepG2 with extremely low expression levels of CYP enzymes. Clinical DILI or non-DILI compounds were evaluated for reactive oxygen species (ROS) production, glutathione (GSH) consumption, and mitochondrial membrane potential (MMP) attenuation. A proportion of DILI compounds induced ROS generation, GSH depletion, and MMP dysfunction, which was consistent with reported mechanisms of DILI of these compounds. In particular, DILI compounds that deplete GSH via reactive metabolites exhibited a more marked decrease in intracellular GSH or increase in ROS production in HepaRG cells than in HepG2 cells. Comparison of the two cell lines with different levels of CYP expression might help clarify the contribution of metabolism to hepatocyte toxicity. These results suggest that the HCA assay in HepaRG and HepG2 cells might help improve the accuracy of evaluating clinical DILI potential during drug screening.

Saito|Junichiro|J| Okamura|Ai|A| Takeuchi|Kenichiro|K| Hanioka|Kenichi|K| Okada|Akinobu|A| Ohata|Takeji|T|

D056486:Chemical and Drug Induced Liver Injury


Assessment of primary health care in a rural health centre in Enugu South east Nigeria.

Abstract:
OBJECTIVE
Primary health care (PHC) is a vital in any community. Any health centre with a well implemented PHC program can stand the test of time in curbing under five mortality and morbidity. This study was therefore aimed at assessing the activities in a health centre located in a rural area in Enugu state and to determine the pattern and presentation of various diseases in the health centre.

METHODS
This is retrospective study undertaken in a primary health care centre in Abakpa Nike in Enugu east LGA of Enugu State of Nigeria from December 2011 to December 31(st) 2013. Data retrieved were collected with the aid of a structured study proforma and analyzed using SPSS Version 18.

RESULTS
Total number of children that attended immunization program in the health centre over 20 months period was 25,438 (12,348 males and 13090 females), however only 17745 children (7998 males and 9747 females) were actually registered in the hospital records. None of the children was immunized for DPT2 and OPV(0) and HBV(1) in the course of this study. The dropout rate using DPT1, 2 and 3 (DPT1-DPT2/DPT3) was very high (494%). The mean immunization coverage rate was 8.3%. Family planning activities, integrated management of childhood illnesses program were also carried out in the health centre but at very low level.

CONCLUSIONS
The major fulcrum of events in the health centre which include immunization coverage, IMCI, and management of common illnesses were simply non operational. However the health centre had a well knitted referral system.

M Chinawa|Josephat|J|
T Chinawa|Awoere|A|

Health centre
Children
Immunization coverage


Preoperative chemoradiotherapy does not compromise the feasibility of adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma.

Abstract:
PURPOSE
Preoperative chemoradiotherapy (CRT) is a novel, emerging treatment strategy for pancreatic ductal adenocarcinoma (PDAC), but it remains unclear whether post-surgery adjuvant chemotherapy is feasible following preoperative CRT. This retrospective study evaluates the feasibility of adjuvant therapy after preoperative CRT.

METHODS
The subjects of this study were 99 consecutive patients who underwent pancreatectomy for PDAC between January, 2007 and February, 2013 in our hospital. Sixty patients received preoperative CRT: as gemcitabine (GEM) and 40 Gy radiation in 28 (G-CRT group), and as GEM, S-1, and 50.4 Gy radiation in 32 (GS-CRT group). We also evaluated 39 patients who underwent surgery alone (SA group). We investigated adjuvant chemotherapy induction and completion rates and the frequency of adverse events rated ≥grade 3, based on Common Terminology Criteria for Adverse Events (version 4.0) in all three groups.

RESULTS
In the G-CRT, GS-CRT, and SA groups, the induction rates were 78 % (22/28), 78 % (25/32), and 72 % (28/39), respectively; completion rates were 86 % (19/22), 88 % (22/25), and 82 % (23/28), respectively; and adverse event frequencies were 36 % (8/22), 28 % (7/25), and 43 % (12/28), respectively. No significant difference was found among the three groups.

CONCLUSION
Preoperative CRT was demonstrated to be safe and did not compromise the feasibility of adjuvant chemotherapy.

Tomihara|Hideo|H| Eguchi|Hidetoshi|H| Yamada|Daisaku|D| Gotoh|Kunihito|K| Kawamoto|Koichi|K| Wada|Hiroshi|H| Asaoka|Tadafumi|T| Noda|Takehiro|T| Takeda|Yutaka|Y| Tanemura|Masahiro|M| Mori|Masaki|M| Doki|Yuichiro|Y|

D000971:Antineoplastic Combined Chemotherapy Protocols

Preoperative chemoradiotherapy
Pancreatic ductal adenocarcinoma
Adverse event
Neoadjuvant chemotherapy


Differential lncRNA expression profiles reveal the potential roles of lncRNAs in antiviral immune response of Crassostrea gigas.

Abstract: Long noncoding RNAs (lncRNAs) may play widespread roles in various biological processes. However, systematic profiles of lncRNAs in the biological responses of Pacific Oyster (Crassostrea gigas) to pathogen infection have not yet been demonstrated. Here, we have conducted an exhaustive comparative transcriptome analysis using a bioinformatics approach to exam the functions of lncRNAs response to Ostreid herpesvirus 1μVar (OsHV-1μVar) challenge. In total, 101 differentially expressed lncRNAs (DE-lncRNA) during OsHV-1μVar infections were identified. Compared with differentially expressed mRNAs (DE-mRNA), DE-lncRNAs are shorter in terms of overall length but longer in terms of exon length. These lncRNAs shared similar characteristics with previously reported invertebrate lncRNAs, such as relatively low GC content, low exon number and low sequence conservation, but low expression level were not observed. 20 DE-lncRNAs are typically co-expressed with their neighboring genes annotated as GO terms (GO: 0044237), indicating that these lncRNAs are involved in binding and cellular process functions in cis mode. The weighted gene co-expression network (WGCNA) analysis resulted in 15 modules. The highlighted blue module was specifically demonstrated a co-expression relationship between 14 DE-lncRNAs and 17 immune-related DE-mRNAs (IR-DE-mRNA). Three hub lncRNAs within this module were co-expressed with one hub IR-DE-mRNA involved in fibrinogen-related protein. It was speculated that lncRNAs is extensively involved in oyster antiviral innate immune system. The present study will facilitate subsequently experimental studies to unravel the function of lncRNAs in marine invertebrate response to pathogen infection.

D000818:Animals
D049896:Crassostrea
D004267:DNA Viruses
D062085:RNA, Long Noncoding
D012333:RNA, Messenger
D017423:Sequence Analysis, RNA

Crassostrea gigas
Long noncoding RNA
Transcriptome analysis
Ostreid herpesvirus
Differentially expression
Innate immune


In silico species identification and serotyping for Cronobacter isolates by use of whole-genome sequencing data.

Abstract: Cronobacter spp. are foodborne pathogens that can cause severe infections in neonates through contaminated powdered infant formula. Accurate and rapid pathogen identification and serotyping are crucial to limit the detrimental effects of bacterial infections, and to prevent outbreaks and sporadic infections. Conventional serotyping is tedious, laborious, and time-consuming; however, with whole-genome sequencing (WGS) becoming faster and cheaper, WGS has vast potential in routine typing and surveillance. Hence, in this study, we developed a publicly available tool, CroTrait (CronobacterTraits), for in silico species identification and O serotyping of Cronobacter isolates based on WGS data. CroTrait showed excellent performance in species identification and O serotyping when 810 genomes with known species identities and 276 genomes with known O serotype were tested. Moreover, CroTrait allows rapid prediction of new potential O serotypes. We identified 11 novel potential O serotypes of Cronobacter using CroTrait. Therefore, CroTrait is a convenient and promising tool for species identification and O serotyping of Cronobacter isolates.

Wang|Lu|L| Zhu|Wenxuan|W| Lu|Gege|G| Wu|Pan|P| Wei|Yi|Y| Su|Yingying|Y| Jia|Tianyuan|T| Li|Linxing|L| Guo|Xi|X| Huang|Min|M| Yang|Qian|Q| Huang|Di|D| Liu|Bin|B|

Species identification
Serotyping
Cronobacter
CroTrait


Lethal and sublethal effects of thiamethoxam, a neonicotinoid molecule, on colony performance of A. mellifera.

Abstract: Among insect pollinators, honey bees, Apis mellifera (Hymenoptera: Apidae), are universally acknowledged, most important managed pollinators that also provide honey production. In recent years, neonicotinoids are widely used against a broad spectrum sucking pests. However, they also pose a major threat to the beekeeping industry. The present study aimed to quantify the impact of thiamethoxam, a second-generation, broad-spectrum neonicotinoid on foraging behavior, colony performance, and survival of Apis mellifera L. in mustard crop under semi-field (cage) and field conditions. Under semi-field conditions, the foraging activity of A. mellifera on mustard bloom reduced significantly on the 2nd day after spray of thiamethoxam as compared to pre-count and control. Significant decrease in brood area (7th to 21st day), nectar stores (7th to 28th day), and pollen stores (7th to 21st day) were also recorded after the spray. The bee mortality under semi-field conditions was significantly higher on the 1st and 2nd day after spray in comparison to control. Under field conditions, average bee activity remained statistically low up to the 12th day after spray on mustard bloom in comparison to pre-count and control. The effect of thiamethoxam under field conditions was less pronounced for bee mortality and colony parameters. Based on LD50, thiamethoxam was proved toxic to adults and larvae of A. mellifera.

Neonicotinoids
Pollinators
Apis mellifera
Mortality
Bee activity
Pesticide toxicity


Relationship Between Thymidine Kinase 1 Expression and Trifluridine/Tipiracil Therapy in Refractory Metastatic Colorectal Cancer: A Pooled Analysis of 2 Randomized Clinical Trials.

Abstract:
BACKGROUND
High thymidine kinase 1 (TK1) activity increases the incorporation of trifluridine (FTD) into DNA; thus, FTD antitumor activity is likely to increase in patients with high tumoral TK1 activity. To date, no established predictive biomarker to indicate the clinical benefit of FTD/tipiracil (TPI) has been identified. We aimed to determine the relationship between TK1 expression and FTD/TPI efficacy in refractory metastatic colorectal cancer.

PATIENTS AND METHODS
Individual patient data from 2 randomized placebo-controlled trials were analyzed. We measured TK1 protein expression in tumor tissue samples and its relationship with FTD/TPI clinical efficacy using overall survival (OS), progression-free survival, and disease control rate.

RESULTS
This study comprised 329 patients (FTD/TPI, 224; placebo, 105). FTD/TPI significantly improved OS versus placebo in the high-expression (cutoff ≥ 15%) TK1 group (median OS, 7.8 vs. 6.8 months; hazard ratio = 0.65; 95% confidence interval, 0.46-0.93; P = .018). The low-expression (cutoff < 15%) TK1 group experienced a smaller OS benefit (9.3 vs. 7.4 months; hazard ratio = 0.88; 95% confidence interval, 0.63-1.23; P = .45). For patients who received placebo, the high-expression TK1 group had a slightly worse prognosis than the low-expression TK1 group. The tendency of FTD/TPI efficacy concerning progression-free survival and disease control rate was not similar to that concerning OS between groups.

CONCLUSION
Patients with high TK1 expression showed an improvement in OS when treated with FTD/TPI. Further investigations are warranted to confirm this relationship.

Yoshino|Takayuki|T| Yamazaki|Kentaro|K| Shinozaki|Eiji|E| Komatsu|Yoshito|Y| Nishina|Tomohiro|T| Baba|Hideo|H| Tsuji|Akihito|A| Tsuji|Yasushi|Y| Yamaguchi|Kensei|K| Sugimoto|Naotoshi|N| Denda|Tadamichi|T| Muro|Kei|K| Takayama|Tetsuji|T| Esaki|Taito|T| Hamamoto|Yasuo|Y| Moriwaki|Toshikazu|T| Shimada|Yasuhiro|Y| Goto|Masahiro|M| Nakayama|Norisuke|N| Fujii|Hirofumi|H| Tanase|Takanori|T| Ohtsu|Atsushi|A|

D016032:Randomized Controlled Trials as Topic

Biomarker
Overall survival
Progression-free survival
Disease control rate
Next-generation sequencing


LONGER CECUM INSERTION TIME AND MORE INADEQUATE COLONIC PREPARATION IN PATIENTS WITH ACROMEGALY: IS A DIFFERENT COLONOSCOPY PREPARATION NEEDED?

Abstract:
Purpose
To investigate whether there is a difference between acromegalic and non-acromegalic cases in terms of bowel preparation and colonoscopic intervention.

Methods
Patients with controlled and uncontrolled acromegaly and as a control group (CG) patients without acromegaly between January 2010 and March 2014 were included. Groups were compared regarding adequacy of bowel preparation, cecal insertion time (CIT) and colonoscopy results.

Results
Fifty-nine patients with acromegaly (controlled n=30, uncontrolled n=29) and 73 age and gender matched volunteers without acromegaly were evaluated. CIT in cases with controlled, uncontrolled acromegaly cases and in CG was 5.33 [4.00-6.00], 7.00 [4.91-11.31], and 3.10 [2.35-4.65] minutes, respectively (p<0.001). Cases in CG had shorter CIT compared to controlled and uncontrolled acromegaly cases ( p=0.014 and p<0.001, respectively). There was no significant difference regarding CIT between controlled and uncontrolled acromegaly cases (p=0.247). Six (20%) of controlled acromegaly patients, 10 (35%) of uncontrolled acromegaly patients and three (4%) of CG had inadequate bowel cleansing (p<0.001). Although statistically insignificant, cases with inadequate bowel cleansing had tendency towards having prolonged CIT in comparison to cases with adequate bowel cleansing (6.00 [3.87-9.00] and 4.16 [2.95-5.70] minutes, respectively, p=0.07).

Conclusion
Inadequate bowel cleansing is one of the main problems encountered during colonoscopic investigation/surveillance in acromegalic patients. Therefore, a different protocol for colonoscopy preparation may be needed for these cases.

Caglar|E|E|
Hatipoglu|E|E|
Atasoy|D|D|
Niyazoglu|M|M|
Çağlar|A S|AS|
Tuncer|M|M|
Dobrucali|A|A|
Kadioglu|P|P|

Acromegaly
colonoscopy
colonoscopy preparation
cecal insertion time
colon cleansing


Ethnobotanical investigation on medicinal plants in Algoz area (South Kordofan), Sudan.

Abstract:
BACKGROUND
The inhabitants of western Sudan use traditional medicine for the treatment of various ailments due to lack of medical doctors and unaffordable prices of pharmaceutical products. The present study is the first documentation of the traditional plant knowledge on medicinal uses of plants by healers in Algoz (South Kordofan), Sudan.

METHOD
Ethnobotanical data were collected over a period from March to November 2015 using semi-structured interviews with 30 healers (24 male and 6 female) living in the investigated area. Quantitative indices such as use categories, use value (UV) and informant consensus factor (ICF) were intended to evaluate the importance of medicinal plant species.

RESULTS
A total of 94 medicinal plants, which belong to 45 families and 81 genera, were recorded in the study area. The most represented families are Leguminosae with 20 species followed by Combretaceae (6 species), Rubiaceae (5 species) and Asteraceae (4 species). The reported species were belonging to herbs (43%), trees (28%), shrubs (22%), climbers (4%) and parasites (3%). Root and stem (21% each) were the most plant parts used. A majority of remedies are administered orally (67%) where infusion (36%) and maceration (32%) are the most used methods. The highest ICF (0.87) was reported for poisonous animal bites followed by urinary system diseases (0.89), blood system disorders (0.88) and gynaecological diseases (0.87). Anastatica hierochuntica, Ctenolepis cerasiformis, Echinops longifolius, Cleome gynandra, Maerua pseudopetalosa, Martynia annua, Oldenlandia uniflora, Opuntia ficus-indica, Solanum dubium, Sonchus cornutus, Tribulus terrestris and Drimia maritima were reported for the first time in this study.

CONCLUSION
The number of medicinal plants reported in this paper reflects evidence that Algoz area had a high diversity of medicinal plants which will continue to play an important role in the healthcare system in the study area.

Issa|Tahani Osman|TO|
Mohamed|Yahya Sulieman|YS|
Yagi|Sakina|S|
Ahmed|Reem Hassan|RH|
Najeeb|Telal Mohammed|TM|
Makhawi|Abdelrafie Mohamed|AM|
Khider|Tarig Osman|TO|

Medicinal plants
Algoz area
Sudan
Healers


Mercury speciation during in situ thermal desorption in soil.

Abstract: Metallic mercury (Hg(0)) and its compounds are highly mobile and toxic environmental pollutants at trace level. In situ thermal desorption (ISTD) is one of the soil remediation processes applying heat and vacuum simultaneously. Knowledge of thermodynamic mercury speciation is imperative to understand the fate and transport of mercury during thermal remediation and operate the treatment processes in a cost-effective manner. Hence, speciation model for inorganic mercury was developed over a range of environmental conditions to identify distribution of dissolved mercury species and potential transformations of mercury at near source environment. Simulation of phase transitions for metallic mercury, mercury(II) chloride and mercury sulfide with temperature increase showed that complete vaporization of metallic mercury and mercury(II) chloride were achieved below the boiling point of water. The effect of soil compositions on mercury removal was also evaluated to better understand thermal remediation process. Higher vapor pressures expected both from soil pore water and inorganic carbonate minerals in soil as well as creation of permeability were significant for complete vaporization and removal of mercury.

Park|Chang Min|CM|
Katz|Lynn E|LE|
Liljestrand|Howard M|HM|

Mercury
Speciation
ISTD
Phase transition
Soil compositions


Cannabis Use in Adolescence and Young Adulthood: A Review of Findings from the Victorian Adolescent Health Cohort Study.

Abstract: The Victorian Adolescent Health Cohort Study (VAHCS) is a long-term Australian cohort study that has documented cannabis use in young Australians from the mid-teens to the mid-30s. The study findings have described the natural history of early cannabis use, remission, and escalation and the social and mental health consequences of different patterns of use. The adverse consequences of cannabis use are most clear-cut in heavy early adolescent users. These consequences include educational failure, persisting mental health problems, and progression to other substance use. For later onset and occasional users, the risks are lower and appear to entail modest elevations in risk for other drug use compared with never users. With growing evidence of health consequences, there is a strong case for actions around early heavy adolescent users. Prevention of early use, identification and treatment of early heavy users, and harm reduction through diversion of early heavy users away from the custodial justice system into health care are all priority responses.


Comparison of patient simulation methods used in a physical assessment course.

Abstract:
OBJECTIVE
To determine whether there is a difference in student pharmacists' learning or satisfaction when standardized patients or manikins are used to teach physical assessment.

DESIGN
Third-year student pharmacists were randomized to learn physical assessment (cardiac and pulmonary examinations) using either a standardized patient or a manikin.

ASSESSMENT
Performance scores on the final examination and satisfaction with the learning method were compared between groups. Eighty and 74 student pharmacists completed the cardiac and pulmonary examinations, respectively. There was no difference in performance scores between student pharmacists who were trained using manikins vs standardized patients (93.8% vs. 93.5%, p=0.81). Student pharmacists who were trained using manikins indicated that they would have probably learned to perform cardiac and pulmonary examinations better had they been taught using standardized patients (p<0.001) and that they were less satisfied with their method of learning (p=0.04).

CONCLUSIONS
Training using standardized patients and manikins are equally effective methods of learning physical assessment, but student pharmacists preferred using standardized patients.

Grice|Gloria R|GR|
Wenger|Philip|P|
Brooks|Natalie|N|
Berry|Tricia M|TM|

physical assessment
standardized patients
manikins
pulmonary examination
cardiac examination


Current concepts in distal humeral hemiarthroplasty.

Abstract: Multi-fragmentary intra-articular fractures of the distal humerus remain a challenge for both patients and surgeons. Open Reduction internal fixation remains the gold standard, however in older patients with comminuted fractures this might not be feasible. There is a growing interest in hemi-arthroplasty as a solution for these cases. However the current experience and follow-up in limited. This review article intends to describe the current concepts in elbow hemiarthroplasty in dept. we will discuss the historical use of these implants, as well as the intricacies of more modern devices. Next we will elaborate an surgical planning, approach, and technical pearls. We will lay out a rehab protocol used by the senior author, and with some considerations for the future.

Jukes|Christopher P|CP|
Dirckx|Margo|M|
Phadnis|Joideep|J|

Hemiarthroplasty
Fracture
Distal humerus
Elbow
Arthroplasty
Trauma


Activation of thromboxane A2 receptors mediates endothelial dysfunction in diabetic mice.

Abstract:
BACKGROUND
Diabetes is one of high-risk factors for cardiovascular disease. Improvement of endothelial dysfunction in diabetes reduces vascular complications. However, the underlying mechanism needs to be uncovered. This study was conducted to elucidate whether and how thromboxane A2 receptor (TPr) activation contributes to endothelial dysfunction in diabetes.

METHODS AND RESULTS
Exposure of human umbilical vein endothelial cells (HUVECs) to either TPr agonists, two structurally related thromboxane A2 (TxA2) mimetics, significantly reduced phosphorylations of endothelial nitric oxide synthase (eNOS) at Ser1177 and Akt at Ser473. These effects were abolished by pharmacological or genetic inhibitors of TPr. TPr-induced suppression of eNOS and Akt phosphorylation was accompanied by upregulation of PTEN (phosphatase and tension homolog deleted on chromosome 10) and Ser380/Thr382/383 PTEN phosphorylation. PTEN-specific siRNA restored Akt-eNOS signaling in the face of TPr activation. The small GTPase, Rho, was also activated by TPr stimulation, and pretreatment of HUVECs with Y27632, a Rho-associated kinase (ROCK) inhibitor, rescued TPr-impaired Akt-eNOS signaling. In mice, streptozotocin-induced diabetes was associated with aortic PTEN upregulation, PTEN-Ser380/Thr382/383 phosphorylation, and dephosphorylation of Akt (at Ser473) and eNOS (at Ser1177). Importantly, administration of TPr antagonist blocked these changes.

CONCLUSION
We conclude that TPr activation impairs endothelial function by selectively inactivating the ROCK-PTEN-Akt-eNOS pathway in diabetic mice.

Xie|Xiaona|X| Sun|Wanchun|W| Wang|Jun|J| Li|Xiaoou|X| Liu|Xiaofeng|X| Liu|Ning|N|

D061307:Human Umbilical Vein Endothelial Cells

D044244:Receptors, Thromboxane A2, Prostaglandin H2

thromboxane A2 receptor
endothelial dysfunction
eNOS
Akt
PTEN


Risk factors for metachronous colorectal cancer following a primary colorectal cancer: A prospective cohort study.

Abstract: Individuals diagnosed with colorectal cancer (CRC) are at risk of developing a metachronous CRC. We examined the associations between personal, tumour-related and lifestyle risk factors, and risk of metachronous CRC. A total of 7,863 participants with incident colon or rectal cancer who were recruited in the USA, Canada and Australia to the Colon Cancer Family Registry during 1997-2012, except those identified as high-risk, for example, Lynch syndrome, were followed up approximately every 5 years. We estimated the risk of metachronous CRC, defined as the first new primary CRC following an interval of at least one year after the initial CRC diagnosis. Observation time started at the age at diagnosis of the initial CRC and ended at the age at diagnosis of the metachronous CRC, last contact or death whichever occurred earliest, or were censored at the age at diagnosis of any metachronous colorectal adenoma. Cox regression was used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). During a mean follow-up of 6.6 years, 142 (1.81%) metachronous CRCs were diagnosed (mean age at diagnosis 59.8; incidence 2.7/1,000 person-years). An increased risk of metachronous CRC was associated with the presence of a synchronous CRC (HR = 2.73; 95% CI: 1.30-5.72) and the location of cancer in the proximal colon at initial diagnosis (compared with distal colon or rectum, HR = 4.16; 95% CI: 2.80-6.18). The presence of a synchronous CRC and the location of the initial CRC might be useful for deciding the intensity of surveillance colonoscopy for individuals diagnosed with CRC.

Jayasekara|Harindra|H|
Reece|Jeanette C|JC|
Buchanan|Daniel D|DD|
Rosty|Christophe|C|
Dashti|S Ghazaleh|SG|
Ait Ouakrim|Driss|D|
Winship|Ingrid M|IM|
Macrae|Finlay A|FA|
Boussioutas|Alex|A|
Giles|Graham G|GG|
Ahnen|Dennis J|DJ|
Lowery|Jan|J|
Casey|Graham|G|
Haile|Robert W|RW|
Gallinger|Steven|S|
Le Marchand|Loic|L|
Newcomb|Polly A|PA|
Lindor|Noralane M|NM|
Hopper|John L|JL|
Parry|Susan|S|
Jenkins|Mark A|MA|
Win|Aung Ko|AK|

risk factors
metachronous
colorectal cancer


Effect of Pt catalyst on the condensable hydrocarbon content generated via food waste pyrolysis.

Abstract: A Pt catalyst supported on activated carbon (Pt/AC) was used for an environmentally friendly thermal treatment of food waste under an inert atmosphere (i.e., pyrolysis). This catalyst influenced the amounts of condensable hydrocarbons and noncondensable gases but not that of the solid remaining after the pyrolysis; in particular, it contributed to shifting the carbon distribution from the condensable hydrocarbons to the noncondensable gases for the food waste pyrolysis. Moreover, its use suppressed the generation of harmful chemical compounds, especially at high temperatures. For example, a Pt/AC-catalyzed pyrolysis at 700 °C produced about 4 times fewer benzene derivatives than the same treatment without a catalyst; this probably occurred because the Pt sites catalyzed the decyclization reaction and/or the free radical mechanism, which is dominant in the thermal cracking of carbon-containing feedstock. This study suggests that a Pt/AC-catalyzed pyrolysis would be a more environmentally benign food waste treatment method.

Kim|Soosan|S|
Lee|Chang-Gu|CG|
Kim|Yong Tae|YT|
Kim|Ki-Hyun|KH|
Lee|Jechan|J|

Catalyst
Food waste
Pyrolysis
Waste disposal
Waste management


Combined photoelectrocatalytic microbial fuel cell (PEC-MFC) degradation of refractory organic pollutants and in-situ electricity utilization.

Abstract: A new photoelectrocatalytic (PEC) and microbial fuel cell (MFC) process was developed and applied to simultaneously remove refractory organic pollutants (i.e., phenol and aniline) from wastewater while recovering energy for in-situ utilization. The current generated by the MFC process was applied to drive the PEC reaction. Compared with single PEC or MFC processes, the PEC-MFC combined process showed higher pollutant and chemical oxygen demand (COD) removal capacities and electricity production. Over 95% of the phenol or aniline was removed by these process, even at high initial concentrations. The COD removal efficiencies for phenol and aniline were ca. 96% (from 700 to 29 mg L-1) and 70% (from 165 to 49 mg L-1), respectively. Although the PEC process showed a limited contribution to phenol and aniline removals (16.5% and 43%, respectively), the utilization of PEC-treated phenol or aniline streams resulted in a MFC with higher voltage output, higher coulombic efficiency, maximal volumetric power density, and lower internal resistance as compared to untreated water. High-performance liquid chromatography coupled with mass spectrometry measurements revealed quinones/hydroquinones and low molecular weight organic acids to be produced as intermediates after the PEC process, which could improve the production of electricity in the MFC.

Zhang|Manman|M| Wang|Ying|Y| Liang|Peng|P| Zhao|Xu|X| Liang|Mingxing|M| Zhou|Bin|B|

D057919:Biological Oxygen Demand Analysis

Microbial fuel cell
Energy recovery
Photoelectrocatalysis
Refractory pollutant


Impact of National Health Mission on infant mortality in India: An interrupted time series analysis.

Abstract: Government of India introduced National Rural Health Mission in 2005-now transformed into National Health Mission (NHM), to bring about architectural reforms in health sector. In this study, we evaluate the overall impact of NHM on infant mortality at national and state level. Annual data on infant mortality rate (IMR) from 1990 to 2016 were obtained from Sample Registration System bulletins. With reporting year 2009 considered as cut-off point, a two-step segmented time series regression analysis was conducted. Estimates of pre-slope, post-slope and change at the point of intervention were computed by applying auto-regressive integrated moving average (1, 0, 0) while adjusting for trend and auto correlation. We found that while IMR reduced from around 80 to 34 per 1000 live births at the national level from 1990 to 2016, the annual rate of reduction increased from 1.6 per 1000 live births before NHM to 2.2 per 1000 live births after NHM. This is estimated to have averted 248,212 infant deaths in India, between 2005 and 2017. The rate of decline in IMR accelerated in 13 out of 17 larger states, most significantly in Andhra Pradesh, Gujarat, Assam, Haryana, Punjab and Uttar Pradesh. NHM has thus been successful in accelerating the overall rate of reduction in IMR in India. There is still a need to identify the determinants of variations at state level. We recommend strengthening of NHM in terms of funding and implementation.

D065186:Interrupted Time Series Analysis

impact
infant mortality
evaluation
programme
statistical analysis


Hydrophobicity and aggregation, but not glycation, are key determinants for uptake of thermally processed β-lactoglobulin by THP-1 macrophages.

Abstract: The aim of this study is to investigate the immunological relevance of modifications of food protein structure due to thermal processing. We investigated the uptake of β-lactoglobulin, treated with 3 different processing methods, by THP-1 macrophages: wet heating (60 °C in solution) and high- or low-temperature (130 °C or 50 °C, respectively) dry heating, combined with either of 8 types of saccharides or without saccharide. The processing method that was applied significantly affected the uptake of BLG by THP-1 macrophages, while the type of saccharide only had an influence in high-temperature dry heated samples. A set of physicochemical parameters of processed samples was determined, to determine the samples' molecular weight, hydrophobicity, amyloid-like structure, surface charge and secondary structure. Analysis of protein structure alterations indicated the uptake to be linked to the wet heating processing method and percentage of α-helix structure, amyloid-like structures, polymers, and hydrophobicity. We hypothesize that both amyloid-like structures and molecular weight were related to the increased hydrophobicity and therefore postulate that the exposure of hydrophobic regions is the leading physicochemical characteristic for the observed uptake of wet heated BLG samples by THP-1 macrophages. This work demonstrates how differential thermal processing of foods, through protein modification, can have an impact on its interaction with the immune system.

Deng|Ying|Y|
Govers|Coen|C|
Bastiaan-Net|Shanna|S|
van der Hulst|Nina|N|
Hettinga|Kasper|K|
Wichers|Harry J|HJ|

D057927:Hydrophobic and Hydrophilic Interactions

Hydrophobicity
Aggregation
Glycation
Uptake
Thermal processing
β-Lactoglobulin
THP-1 macrophage


Drug Burden Index and Its Association With Hip Fracture Among Older Adults: A National Population-Based Study.

Abstract:
BACKGROUND
The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study was to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors.

METHODS
A competing-risks regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (International Resident Assessment Instrument) assessment between September 1, 2012, and October 31, 2015, the study's end date. Outcome measures were survival status and hip fracture, with time-varying DBI exposure derived from 90-day time intervals. The multivariable competing-risks regression model was adjusted for a large number of medical comorbidities and activities of daily living.

RESULTS
Among 70,553 adults assessed, 2,249 (3.2%) experienced at least one hip fracture, 20,194 (28.6%) died without experiencing a fracture, and 48,110 (68.2%) survived without a fracture. The mean follow-up time was 14.9 months (range: 1 day, 37.9 months). The overall DBI distribution was highly skewed, with median time-varying DBI exposure ranging from 0.93 (Q1 = 0.0, Q3 = 1.84) to 0.96 (Q1 = 0.0, Q3 = 1.90). DBI was significantly related to fracture incidence in unadjusted (p < .001) and adjusted (p < .001) analyses. The estimated subhazard ratio was 1.52 (95% confidence interval: 1.28-1.81) for those with DBI > 3 compared with those with DBI = 0 in the adjusted analysis.

CONCLUSIONS
In this study, increasing DBI was associated with a higher likelihood of fractures after accounting for the competing risk of mortality and adjusting for confounders. The results of this unique study are important in validating the DBI as a guide for medication management and it could help reduce the risk of hip fractures in older adults.

Jamieson|Hamish A|HA|
Nishtala|Prasad S|PS|
Scrase|Richard|R|
Deely|Joanne M|JM|
Abey-Nesbit|Rebecca|R|
Hilmer|Sarah N|SN|
Abernethy|Darrell R|DR|
Berry|Sarah D|SD|
Mor|Vincent|V|
Lacey|Cameron J|CJ|
Schluter|Philip J|PJ|

D000058:Accidental Falls
D000203:Activities of Daily Living
D000368:Aged
D018680:Cholinergic Antagonists
D005260:Female
D006620:Hip Fractures
D006801:Humans
D006993:Hypnotics and Sedatives
D015994:Incidence
D057187:Independent Living
D008297:Male
D054539:Medication Therapy Management
D009520:New Zealand
D018570:Risk Assessment
D012307:Risk Factors


Clinical presentation and diagnosis of multiple sclerosis.

Abstract: The diagnosis of multiple sclerosis (MS) is through clinical assessment and supported by investigations. There is no single accurate and reliable diagnostic test. MS is a disease of young adults with a female predominance. There are characteristic clinical presentations based on the areas of the central nervous system involved, for example optic nerve, brainstem and spinal cord. The main pattern of MS at onset is relapsing-remitting with clinical attacks of neurological dysfunction lasting at least 24 hours. The differential diagnosis includes other inflammatory central nervous system disorders. Magnetic resonance imaging of the brain and lumbar puncture are the key investigations. New diagnostic criteria have been developed to allow an earlier diagnosis and thus access to effective disease modifying treatments.


Contribution of Iran in COVID-19 studies: a bibliometrics analysis.

Abstract:
Background
Iran is fighting heroically against COVID-19. Due to the importance of scientific publications in better dealing with this stubborn virus, this study was conducted aiming at reviewing COVID-19 publications by Iranian scientists.

Methods
We searched for COVID-19 and all its related keywords in the Web of Science (WOS), Scopus and PubMed databases to find documents published by Iranian authors until July 10, 2020. Duplicates documents were excluded, and bibliographic parameters were evaluated. Co-authorship matrix was calculated using Bibexcel, and visualizations were done using VOSviewer.

Results
A total of 849 documents from 3450 Iranian researchers (5.5 authors per document) were retrieved from WOS, PubMed, and Scopus and Iran ranked 12th and 13th in WOS and Scopus in terms of the number of publications. The average citation per document was 2.2 with the h-index of 18. Original articles and letters were the most common formats for Iranian publications. The Journal of Military Medicine has published the highest number of documents. Iranian authors have mostly collaborated with researchers from the United States, Italy, the UK, and Canada, respectively. The co-occurrence network for keywords represented five publication clusters in the collection, and the largest clusters were related to epidemiological studies and public health, followed by clinical studies on COVID-19.

Conclusion
Iranian researchers have had a significant scientific contribution in various areas of the disease. However, the network of studies has not been sufficiently cohesive, and more coherent collaboration between researchers at the national and international levels should be on the agenda of research policymakers in the country.

Iran COVID-19 Bibliometrics Publications Coronavirus SARS-CoV-2


Network monitoring of adhesion/growth-regulatory galectins: localization of the five canonical chicken proteins in embryonic and maturing bone and cartilage and their introduction as histochemical tools.

Abstract: Divergence from an ancestral gene leads to a family of homologous proteins. Whether they are physiologically distinct, similar, or even redundant is an open question in each case. Defining profiles of tissue localization is a step toward giving diversity a functional meaning. Due to the significance of endogenous sugar receptors (lectins) as effectors for a wide range of cellular activities we have focused on galectins. The comparatively low level of network complexity constituted by only five canonical proteins makes chicken galectins (CGs) an attractive choice to perform comprehensive analysis, here studied on bone/cartilage as organ system. Galectin expression was monitored by Western blotting and immunohistochemistry using non-cross-reactive antibodies. Overall, three galectins (CG-1B, CG-3, CG-8) were present with individual expression patterns, one was found exclusively in the mesenchyme (CG-1A), the fifth (CG-2) not being detectable. The documented extents of separation are a sign for functional divergence; in cases with overlapping stainings, as for example in the osteoprogenitor layer or periosteum, cooperation may also be possible. Recombinant production enabled the introduction of the endogenous lectins as tools for binding-site localization. Their testing revealed developmental regulation and cell-type-specific staining. Of relevance for research on mammalian galectins, this study illustrates that certain cell types can express more than one galectin, letting functional interrelationships appear likely. Thus, complete network analysis irrespective of its degree of complexity is mandatory.

Kaltner|Herbert|H|
Singh|Tanuja|T|
Manning|Joachim C|JC|
Raschta|Anne-Sarah|AS|
André|Sabine|S|
Sinowatz|Fred|F|
Gabius|Hans-Joachim|HJ|

D036341:Intercellular Signaling Peptides and Proteins

lectin mesenchyme chondrocyte glycoconjugate osteoblast


Heterogeneous blood flow in microvessels with applications to nanodrug transport and mass transfer into tumor tissue.

Abstract: Nanodrug transport in tumor microvasculature and deposition/extravasation into tumor tissue are an important link in the nanodrug delivery process. Considering heterogeneous blood flow, such a dual process is numerically studied. The hematocrit distribution is solved by directly considering the forces experienced by the red blood cells (RBCs), i.e., the wall lift force and the random cell collision force. Using a straight microvessel as a test bed, validated computer simulations are performed to determine blood flow characteristics as well as the resulting nanodrug distribution and extravasation. The results confirm that RBCs migrate away from the vessel wall, leaving a cell-free layer (CFL). Nanodrug particles tend to preferentially accumulate in the CFL, leading to increased concentration near the endothelial surface layer. However, shear-induced NP diffusion is diminished within the CFL, causing to a much slower lateral transport rate into tumor tissue. These competing effects determine the NP deposition/extravasation rates. The present modeling framework and NP flux results provide new physical insight. The analysis can be readily extended to simulations of NP transport in blood microvessels of actual tumors.

Extravasation
Nanodrug delivery
Computer simulation
Cell-free layer


Long-Term Effectiveness of a Drug-Eluting Stent for Femoropopliteal In-Stent Restenosis: Subanalysis of the Zilver PTX Japan Post-Market Surveillance Study.

Abstract:
PURPOSE
To present a subgroup analysis of patients from a large real-world study evaluating the safety and effectiveness of the Zilver PTX drug-eluting stent (DES) for treating femoropopliteal in-stent restenosis (ISR).

MATERIALS AND METHODS
This study examined patients enrolled in the Zilver PTX Japan Post-Market Surveillance Study (ClinicalTrials.gov identifier NCT02254837), a prospective, multicenter registry of 904 symptomatic patients with 1082 femoropopliteal lesions treated with the DES at 95 institutions in Japan. Five-year outcomes, including mortality, stent radiography, freedom from target lesion revascularization (TLR), and clinical benefit, were evaluated for 177 patients (mean age 74.2±8.3 years; 118 men) with 204 ISR lesions treated with the Zilver DES. Over half of the patients (108, 61.0%) were diabetic. Mean lesion length was 17.8±10.4 cm, and a third (72, 35.3%) were total occlusions. Outcome measures were all-cause mortality, thrombosis, freedom from TLR, and clinical benefit, defined as freedom from persistent or deteriorating ischemic symptoms.

RESULTS
No device-related or procedure-related deaths or paclitaxel-related adverse events were reported. All-cause mortality was 25.1% at 5 years. Stent fracture was observed in 5 stents through 5 years. The 5-year rate of freedom from clinically-driven TLR was 73.4%, and the rate of clinical benefit was 63.6%. Improvement in Rutherford category and ankle-brachial index was sustained through 5 years.

CONCLUSION
The safety and effectiveness of the Zilver PTX stent for the treatment of femoropopliteal ISR lesions demonstrated that this device provides a favorable treatment option in this difficult-to-treat subgroup.

drug-eluting stent
in-stent restenosis
mortality
target lesion revascularization
occlusion
peripheral artery disease


Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 14: brace therapy as an adjunct to or substitute for lumbar fusion.

Abstract: The utilization of orthotic devices for lumbar degenerative disease has been justified from both a prognostic and therapeutic perspective. As a prognostic tool, bracing is applied prior to surgery to determine if immobilization of the spine leads to symptomatic relief and thus justify the performance of a fusion. Since bracing does not eliminate motion, the validity of this assumption is questionable. Only one low-level study has investigated the predictive value of bracing prior to surgery. No correlation between response to bracing and fusion outcome was observed; therefore a trial of preoperative bracing is not recommended. Based on low-level evidence, the use of bracing is not recommended for the prevention of low-back pain in a general working population, since the incidence of low-back pain and impact on productivity were not reduced. However, in laborers with a history of back pain, a positive impact on lost workdays was observed when bracing was applied. Bracing is recommended as an option for treatment of subacute low-back pain, as several higher-level studies have demonstrated an improvement in pain scores and function. The use of bracing following instrumented posterolateral fusion, however, is not recommended, since equivalent outcomes have been demonstrated with or without the application of a brace.

Dailey|Andrew T|AT|
Ghogawala|Zoher|Z|
Choudhri|Tanvir F|TF|
Watters|William C|WC|
Resnick|Daniel K|DK|
Sharan|Alok|A|
Eck|Jason C|JC|
Mummaneni|Praveen V|PV|
Wang|Jeffrey C|JC|
Groff|Michael W|MW|
Dhall|Sanjay S|SS|
Kaiser|Michael G|MG|

D019317:Evidence-Based Medicine
D006801:Humans
D008159:Lumbar Vertebrae
D009989:Orthotic Devices
D017410:Practice Guidelines as Topic
D013122:Spinal Diseases
D013123:Spinal Fusion

RMDQ = Roland-Morris Disability Questionnaire

RSA = roentgen stereophotogrammetric analysis

SF-12 = 12-Item Short Form Health Survey

SF-36 = 36-Item Short Form Health Survey

TEPF = temporary external pedicle fixation


Primary Cutaneous B-Cell Lymphoma in Young Monozygotic Twins: A Case Report.

Abstract: Although familial aggregation of lymphoproliferative disorders has been described, heredity has not been implicated in the etiology of primary cutaneous B-cell lymphomas (PCBCL). We report herein the first case of 2 young monozygotic twins with PCBCL. The first twin was an 18-year-old woman when she presented with multiple skin nodules on the thorax and head. Histology showed an atypical small B-cell proliferation, consistent with primary cutaneous marginal zone lymphoma (PCMZL). Molecular genetics studies demonstrated B-cell clonality. Seven years later, the second twin developed her first lesion that was histologically similar to that of her twin. She subsequently developed other clinically similar lesions. Histology was consistent with PCMZL and showed B-cell clonality. Occurrence of PCBCL in these monozygotic twins raises the possibility of a genetic risk factor. Further study of such rare cases may offer valuable insights into the molecular basis of the etiology and pathogenesis of this unusual disorder.

Bahig|Houda|H|
Petrogiannis-Haliotis|Tina|T|
Pehr|Kevin L|KL|
Roberge|David|D|


Niobium silicate particles promote in vitro mineral deposition on dental adhesive resins.

Abstract:
OBJECTIVE
This study aims to analyze the addition of niobium silicate particles to dental adhesive resins and evaluate its physicomechanical and biological properties.

METHODS
The SiNb particles were produced by the sol-gel route and presented a mean particle size of 2.1 μm and a specific surface area of 616,96m2/g. An experimental adhesive resin was formulated with 66 wt% Bisphenol A-Glycidyl Methacrylate and 33 wt% Hydroxyethyl methacrylate with diphenyl(2,4,6-trimethyl benzoyl)phosphine oxide as the photoinitiator. The SiNb particles were incorporated into the adhesive resins in 1 wt% (SiNb1%) and 2 wt% (SiNb2%) concentration. A control group (SiNb0%) without the addition of particles was used. The developed adhesives were evaluated by their polymerization kinetics, refractive index, softening in solvent, cytotoxicity, mineral deposition, ultimate tensile strength, and micro shear bond strength.

RESULTS
The refractive index range was increased by the addition of niobium silicate particles. No statistically significant difference was found between groups in the degree of conversion,.softening in solvent analysis, cytotoxicity and ultimate tensile strength. The deposition of minerals increased after immersion of specimens in SBF after 14 days on the SiNb2%. The SiNb2% group showed high micro shear bond strength values, reaching 33.87 MPa.

CONCLUSION
In the present study, the addition of 2 wt% of niobium silicate into dental adhesive resins promoted the mineral deposition with increased bond strength without affecting other material properties.

CLINICAL SIGNIFICANCE
Bioactive fillers must maintain the physical-chemical properties of dental adhesives, guaranteeing their clinical performance. Niobium silicate particles could promote the remineralization of dentin hard tissues without compromising the physico-mechanical properties on these materials.

Balbinot|G S|GS|
Leitune|V C B|VCB|
Ogliari|F A|FA|
Collares|F M|FM|


Prereactivation propranolol fails to reduce skin conductance reactivity to prepared fear-conditioned stimuli.

Abstract: Pharmacologic blockade of memory reconsolidation has been demonstrated in fear-conditioned rodents and humans and may provide a means to reduce fearfulness in anxiety disorders and posttraumatic stress disorder. Studying the efficacy of potential interventions in clinical populations is challenging, creating a need for paradigms within which candidate reconsolidation-blocking interventions can be readily tested. We used videos of biologically prepared conditioned stimuli (tarantulas) to test the efficacy of propranolol in blocking reconsolidation of conditioned fear in healthy young adults. Strong differential conditioning, measured by skin conductance, was observed among a screened subset of participants during acquisition. However, subsequent propranolol failed to reduce reactivity to the reactivated conditioned stimulus. These results are consistent with other recent findings and point to a need for testing other candidate drugs.

Spring|Justin D|JD|
Wood|Nellie E|NE|
Mueller-Pfeiffer|Christoph|C|
Milad|Mohammed R|MR|
Pitman|Roger K|RK|
Orr|Scott P|SP|

Propranolol
Skin conductance
Reconsolidation
Fear conditioning
Posttraumatic stress disorder (PTSD)


A Rapid Review and Narrative Synthesis of the Consequences of Non-Inclusive Sex Education in UK Schools on Lesbian, Gay, Bisexual, Transgender and Questioning Young People.

Abstract: Relationships and Sex Education (RSE) in schools are predominantly heterocentric. Consequently, lesbian, gay, bisexual, transgender, and questioning young people have reported feeling excluded. This exclusion results in feelings of being "different" and "other," which in turn leads to further disengagement in the sex education classroom, contributing to poor sexual health literacy, greater risk of abusive relationships, and higher rates of sexually transmitted infections. A rapid review was undertaken to identify the impact of non-inclusive sex education. The review makes recommendations for policy and practice, which includes the provision of training courses to school teaching staff with an emphasis on inclusive RSE, appropriate online resources for lesbian, gay, bisexual transgender, and questioning (LGBTQ) young people, as well as offering 1:1 emotional health support for LGBTQ young people as they begin to question their sexual orientation.

lesbian
gay
questioning
relationship and sex education
inclusive RSE
bisexual transgender
health education
middle/junior/high school