Epstein-Barr Virus-Positive T/NK-Cell Lymphoproliferative Diseases in Chinese Mainland.

Abstract: Epstein-Barr virus-positive T/NK-cell lymphoproliferative disorders (EBV+ T/NK LPD) encompass a heterogeneous group of disorders, including chronic active Epstein-Barr virus infection (CAEBV), Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH), systemic EBV+ T-cell lymphoma of childhood and hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) and so on, predominantly affecting children and young adults with high mortality. Patients with EBV+ T/NK LPD have overlapping clinical symptoms as well as histologic and immunophenotypic features. In this review, we summarized the clinical features of EBV+ T/NK LPD in Chinese patients from the published articles.

lymphoproliferative disorder
Epstein-Barr virus
clinical feature
China
T/natural killer cell


Histoplasmosis Diagnosed in Europe and Israel: A Case Report and Systematic Review of the Literature from 2005 to 2020.

Abstract: Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%.

histoplasmosis
Histoplasma capsulatum
travellers
immunocompromise
HIV
diagnosis
progressive disseminated histoplasmosis
Histoplasma duboisii


Nanocrystals Technology for Improving Bioavailability of Poorly Soluble Drugs: A Mini-Review.

Abstract: Nanocrystals technology for water insoluble drugs delivery has been expanding exponentially, as a robust approach, over the last ten years. Drug nanocrystals are sub-micron colloidal dispersion system of pure drug nanoparticles. Compared to the traditional pharmaceutical dosage forms, nano-crystals formulation presented many extraordinary properties such as enhanced dissolution rate and saturation solubility, high drug loading, excellent reproducibility of oral absorption, improved proportionality of dose-bioavailability, and increased patient compliance. This review explains the bioavailability improving mechanism in drug delivery to present the state-of-art nanocrystals. The physically stable nanocrystals with appropriate particle size and zeta potential could be prepared by screening of stabilizing agents. The marketed nanocrystal products and drug safety issues about the technology are also discussed. Moreover, the perspectives and challenges about improving nanocrystals investigated in this review could provide guidance for further study. Thus, this article could serve as a reference for optimizing the bioavailability of a specific drug candidate.

Zhou|Yuqi|Y| Du|Juan|J| Wang|Lulu|L| Wang|Yancai|Y|

Nanocrystals
Bioavailability
Solubility
Dissolution Rate


Influence of maternal care on the developing brain: Mechanisms, temporal dynamics and sensitive periods.

Abstract: Variation in maternal care can lead to divergent developmental trajectories in offspring with implications for neuroendocrine function and behavioral phenotypes. Study of the long-term outcomes associated with mother-infant interactions suggests complex mechanisms linking the experience of variation in maternal care and these neurobiological consequences. Through integration of genetic, molecular, cellular, neuroanatomical, and neuroendocrine approaches, significant advances in our understanding of these complex pathways have been achieved. In this review, we will consider the impact of maternal care on male and female offspring development with a particular focus on the issues of timing and mechanism. Identifying the period of sensitivity to maternal care and the temporal dynamics of the molecular and neuroendocrine changes that are a consequence of maternal care represents a critical step in the study of mechanism.

Curley|James P|JP|
Champagne|Frances A|FA|

Maternal
Development
Sensitive period
Offspring
Timing
Epigenetic


Streptomyces phaeolivaceus sp. nov. and Streptomyces broussonetiae sp. nov., isolated from the leaves and rhizosphere soil of Broussonetia papyrifera.

Abstract: Two novel actinobacteria, designated strains GY16T and T44T, were isolated from the leaves and rhizosphere soil of Broussonetia papyrifera, respectively. A polyphasic approach was used for determining their taxonomic position. Results of 16S rRNA gene sequence analysis indicated that strain GY16T exhibited highest similarities to Streptomyces cinereoruber subsp. fructofermentans CGMCC 4.1593T (98.82 %), Streptomyces deccanensis KCTC 19241T (98.76 %), Streptomyces scabiei NRRL B-16523T (98.69 %), Streptomyces europaeiscabiei KACC 20186T (98.69 %) and Streptomyces rishiriensis NBRC 13407T (98.69 %), and strain T44T showed 99.2, 99.1, 99.1 and <98.7 % sequence similarities to Streptomyces filipinensis CGMCC 4.1452T, Streptomyces achromogenes subsp. achromogenes DSM 40028T, Streptomyces durhamensis DSM 40539T and other Streptomyces species, respectively. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain GY16T formed an independent subclade, which indicated that strain GY16T should belong to a potential novel species; and strain T44T was closely related to S. filipinensis CGMCC 4.1452T, S. achromogenes subsp. achromogenes DSM 40028T, S. durhamensis DSM 40539T and S. yokosukanensis DSM 40224T. However, the multilocus sequence analysis evolutionary distance, average nucleotide identity and DNA-DNA hybridization values between closely related relatives were far from the species-level thresholds. In addition, phenotypic and chemotaxonomic characteristics further confirmed that strains GY16T and T44T belonged to two distinct species. Based on these results, it is concluded that the isolated strains represent novel species within the genus Streptomyces, for which the names Streptomyces phaeolivaceus sp. nov. (type strain GY16T=CICC 24807T=KCTC 49326T) and Streptomyces broussonetiae sp. nov. (type strain T44T=CICC 24819T=JCM 33918T) are proposed.

Mo|Ping|P| Liu|Jun|J| Zhao|Yunlin|Y| Xu|Zhenggang|Z|

Streptomyces phaeolivaceus sp. nov.
Streptomyces broussonetiae sp. nov.
Broussonetia papyrifera
polyphasic taxonomy


Hashimoto's thyroiditis and papillary thyroid cancer: are they immunologically linked?

Abstract: Hashimoto's thyroiditis (HT) is the most common autoimmune disease in humans frequently leading to hypothyroidism. HT is characterized by a cellular immune response with lymphatic infiltration of the thyroid gland by T and B cells, as well as by a humoral immune response leading to specific antibody production. The synchronous appearance of HT and papillary thyroid cancer (PTC) indicates an immunological link between the two entities. Three different pathomechanisms may be postulated, including preexisting autoimmunity leading to malignancy due to inflammation, immunity towards preexisiting tumor cells leading to specific autoimmunity, and immune tolerance leading to malignancy despite (auto)immunity. In this article we review data describing these potential mechanisms that might lead to the synchronous appearance of HT and PTC.

D002277:Carcinoma
D002291:Carcinoma, Papillary
D050031:Hashimoto Disease
D006801:Humans
D007111:Immunity, Cellular
D000077273:Thyroid Cancer, Papillary
D013961:Thyroid Gland
D013964:Thyroid Neoplasms

Hashimoto's thyroiditis
cellular immunity
thyroid gland
papillary thyroid carcinoma


Biomechanical function requirements of the wrist. Circumduction versus flexion/abduction range of motion.

Abstract: The biomechanical function of the wrist is widely assessed by measuring the range of motion (RoM) in two separate orthogonal planes: flexion-extension (FE) and radioulnar deviation (RUD). However, the two motions are coupled. The aim of this study is to compare wrist circumduction with FE and RUD RoM in terms of representativeness of the kinematic requirements for performing activities of daily living (ADL). To this end, the wrist motion of healthy participants was measured while performing maximum RoM in FE and in RUD, circumduction, and thirty-two representative ADL. Active and functional RoM (ARoM and FRoM) were computed in each plane, the evolving circumduction curves were adjusted to ellipses, and intensity maps representing the frequency of the coupling angles in ADL were plotted, both per ADL and globally for both hands. Ellipses representing different percentages of coupling angles in ADL were also plotted. Wrist circumduction fits the coupling angles measured in ADL better than ARoM or FRoM. As a novelty, quantitative data for both circumduction and the coupling angles required in ADL are provided, shedding light on the real biomechanical function requirements of the wrist. Results might be used to quantify mobility reduction and its impact on the performance of ADL, globally and per ADL, to enhance rehabilitation strategies, as well as in clinical decision-making, robotics, and prostheses.

Gracia-Ibáñez|Verónica|V|
Sancho-Bru|Joaquín L|JL|
Vergara|Margarita|M|
Roda-Sales|Alba|A|
Jarque-Bou|Néstor J|NJ|
Bayarri-Porcar|Vicente|V|

Biomechanical function requirements
Wrist circumduction


Laboratory real-time and in situ monitoring of mechanochemical milling reactions by Raman spectroscopy.

Abstract: Mechanistic understanding of mechanochemical reactions is sparse and has been acquired mostly by stepwise ex situ analysis. We describe herein an unprecedented laboratory technique to monitor the course of mechanochemical transformations at the molecular level in situ and in real time by using Raman spectroscopy. The technique, in which translucent milling vessels are used that enable the collection of a Raman scattering signal from the sample as it is being milled, was validated on mechanochemical reactions to form coordination polymers and organic cocrystals. The technique enabled the assessment of the reaction dynamics and course under different reaction conditions as well as, for the first time, direct insight into the behavior of liquid additives during liquid-assisted grinding.

Gracin|Davor|D| Štrukil|Vjekoslav|V| Friščić|Tomislav|T| Halasz|Ivan|I| Užarević|Krunoslav|K|

Raman spectroscopy
liquid-assisted grinding
in situ techniques
mechanochemistry
reaction mechanisms


Toxicogenomic applications of Chinese rare minnow (Gobiocypris rarus) in aquatic toxicology.

Abstract: Rare minnow (Gobiocypris rarus), a Chinese native species, are an excellent emerging model organism for aquatic toxicity testing and chemical safety assessment. "Big data" omics approaches (i.e., genomics, proteomics, and metabolomics) to inform mechanistic toxicology are now applied to studies in rare minnows to better understand toxicity and molecular pathways perturbed by chemicals. This review highlights recent applications of toxicogenomics to study changes in the gene and protein expression profiles in rare minnows in response to chemicals. Here we briefly describe studies that utilized cDNA microarrays in characterization of the cellular effects of rare minnows in single and mixed chemical exposures. Then we compare gel-based proteomics studies in liver of rare minnows following treatment with endocrine disrupting chemicals including 17β-estradiol, 17α-methyltestosterone, pentachlorophenol, and perfluorooctanoic acid. A total of 90 proteins identified in these studies were functionally annotated and categorized. These responsive proteins have roles in biological processes that include metabolism (37.8%), response to oxidation/chemicals (16.7%), signal transduction (11.1%), transport (10%), cytoskeleton (6.7%) and others (17.8%). In addition, recent investigations of endocrine disrupting effects and neurotoxicity of benzotriazole, an emerging contaminant, are summarized. The objective is to continue to enrich genome and protein databases for this species and to integrate molecular datasets to consider temporal effects and complex regulation at the level of the genome and proteome.

Toxicogenomics
Rare minnow (Gobiocypris rarus)
Proteomics
Microarray
Endocrine disrupting chemical


Characterization of background noise in MiSeq MPS data when sequencing human mitochondrial DNA from various sample sources and library preparation methods.

Abstract: Improved resolution of massively parallel sequencing (MPS) allows for the characterization of mitochondrial (mt) DNA heteroplasmy to levels previously unattainable with traditional sequencing approaches. An essential criterion for the reporting of heteroplasmy is the ability of the MPS method to distinguish minor sequence variants (MSVs) from system noise, or error. Therefore, an assessment of the background noise in the MPS method is desirable to identify the point at which reliable data can be reported. Substitution and sequence specific error (SSE) was evaluated for a variety of sample types and two library preparations. Substitution error rates ranged from 0.18 to 0.49 per 100 nucleotides with C positions generally having the highest rate of misincorporation. Comparison of error rates across sample types indicated a significant increase for samples with damaged DNA. The positions of error were varied across datasets (pairwise concordance 0-68%), but had greater consistency within the damaged samples (80-96%). The most commonly observed motif preceding error in forward reads was CCG, while GGT was most common in reverse reads, both consistent with previous findings. The findings illustrate that for datasets containing samples with damaged DNA, reporting thresholds for heteroplasmy may have to be modified and individual sites with error levels exceeding thresholds should be scrutinized. Collectively, the shifting error profiles observed across the various sample types and library preparation methods demonstrates the need for an assessment of error under these varying circumstances. Characterization of the applicable background noise will help to ensure that thresholds are reliably set for detection of true MSVs.

McElhoe|Jennifer A|JA|
Holland|Mitchell M|MM|

Massively parallel sequencing
Minor sequence variants
Error rates
DNA damage
Forensic DNA
Next generation sequencing


Comparing the mental health literacy of Chinese people in Australia, China, Hong Kong and Taiwan: Implications for mental health promotion.

Abstract: Using data of 200, 522, 572, and 287 Chinese from Australia, China, Hong Kong and Taiwan respectively, this study aimed at comparing the mental health literacy of Chinese people from different communities, and between Chinese communities and the Australian general public. The participants were asked questions that assessed their recognition of depression and schizophrenia. Compared with the Australians, much lower percentages of Chinese in the four Chinese communities could correctly identify depression and early schizophrenia. Commonalities in the preference for 'psychiatrist', 'psychologist', 'Chinese medical doctor', and 'Chinese traditional healer', a lack of knowledge of medications, and a higher likelihood of endorsement of traditional Chinese medicines were found among the four Chinese communities. Differences in the preference for 'general practitioner' and 'social worker', and a higher percentage of endorsement of herbal medicines were observed among the different Chinese communities. Cultural factors such as Chinese perceptions of mental illness, and socio-contextual factors such as differences in mental health care system in the four communities were offered to explain these commonalities and differences. Mental health promotion programmes for Chinese people may need to consider the above-mentioned cultural and socio-contextual factors so that specific promotion programmes can be developed.

Wong|Daniel Fu Keung|DFK|
Cheng|Chi-Wei|CW|
Zhuang|Xiao Yu|XY|
Ng|Ting Kin|TK|
Pan|Shu-Man|SM|
He|Xuesong|X|
Poon|Ada|A|

Mental health
Chinese culture
Cross-cultural comparison
Depression literacy
Schizophrenia literacy


Testing reticulate versus coalescent origins of Erica lusitanica using a species phylogeny of the northern heathers (Ericeae, Ericaceae).

Abstract: Whilst most of the immense species richness of heathers (Calluna, Daboecia and Erica: Ericeae; Ericaceae) is endemic to Africa, particularly the Cape Floristic Region, the oldest lineages are found in the Northern Hemisphere. We present phylogenetic hypotheses for the major clades of Ericeae represented by multiple accessions of all northern Erica species and placeholder taxa for the large nested African/Madagascan clade. We identified consistent, strongly supported conflict between gene trees inferred from ITS and chloroplast DNA sequences with regard to the position of Erica lusitanica. We used coalescent simulations to test whether this conflict could be explained by coalescent stochasticity, as opposed to reticulation (e.g. hybridisation), given estimates of clade ages, generation time and effective population sizes (Ne). A standard approach, comparing overall differences between real and simulated trees, could not clearly reject coalescence. However, additional simulations showed that at the (higher) Ne necessary to explain conflict in E. lusitanica, further topological conflict would also be expected. Ancient hybridisation between ancestors of northern species is therefore a plausible scenario to explain the origin of E. lusitanica, and its morphological similarities to E. arborea. Assuming either process influences the results of species tree and further evolutionary inference. The coalescence scenario is equivocal with regard the standing hypothesis of stepping stone dispersal of Erica from Europe into Africa; whereas reticulate evolution in E. lusitanica would imply that the colonisation of Tropical East Africa by E. arborea instead occurred independently of dispersals within the rest of the African/Madagascan clade.

Mugrabi de Kuppler|A L|AL|
Fagúndez|J|J|
Bellstedt|D U|DU|
Oliver|E G H|EG|
Léon|J|J|
Pirie|M D|MD|

Erica
Calluna
Daboecia
Coalescent stochasticity
Hybridisation
Reticulate evolution


Diabetes Mellitus in a Patient With Lafora Disease: Possible Links With Pancreatic β-Cell Dysfunction and Insulin Resistance.

Abstract: Lafora disease (LD) is a rare autosomal recessive disorder characterized by progressive myoclonic epilepsy followed by continuous neurological decline, culminating in death within 10 years. LD leads to accumulation of insoluble, abnormal, glycogen-like structures called Lafora bodies (LBs). It is caused by mutations in the gene encoding glycogen phosphatase (EPM2A) or the E3 ubiquitin ligase malin (EPM2B/NHLRC1). These two proteins are involved in an intricate, however, incompletely elucidated pathway governing glycogen metabolism. The formation of EPM2A and malin signaling complex promotes the ubiquitination of proteins participating in glycogen metabolism, where dysfunctional mutations lead to the formation of LBs. Herein, we describe a 13-years-old child with LD due to a NHLRC1 (c.386C > A, p.Pro129His) mutation, who has developed diabetes mellitus and was treated with metformin. We discuss how basic mechanisms of LD could be linked to β-cell dysfunction and insulin resistance.

Nicolescu|Ramona C|RC|
Al-Khawaga|Sara|S|
Minassian|Berge A|BA|
Hussain|Khalid|K|

diabetes
Lafora disease
insulin resistance
EPM2A
EPM2B/NHLRC1
glycogen metabolism


Understanding mutation hotspots for the SARS-CoV-2 spike protein using Shannon Entropy and K-means clustering.

Abstract: The SARS-CoV-2 virus like many other viruses has transformed in a continual manner to give rise to new variants by means of mutations commonly through substitutions and indels. These mutations in some cases can give the virus a survival advantage making the mutants dangerous. In general, laboratory investigation must be carried to determine whether the new variants have any characteristics that can make them more lethal and contagious. Therefore, complex and time-consuming analyses are required in order to delve deeper into the exact impact of a particular mutation. The time required for these analyses makes it difficult to understand the variants of concern and thereby limiting the preventive action that can be taken against them spreading rapidly. In this analysis, we have deployed a statistical technique Shannon Entropy, to identify positions in the spike protein of SARS Cov-2 viral sequence which are most susceptible to mutations. Subsequently, we also use machine learning based clustering techniques to cluster known dangerous mutations based on similarities in properties. This work utilizes embeddings generated using language modeling, the ProtBERT model, to identify mutations of a similar nature and to pick out regions of interest based on proneness to change. Our entropy-based analysis successfully predicted the fifteen hotspot regions, among which we were able to validate ten known variants of interest, in six hotspot regions. As the situation of SARS-COV-2 virus rapidly evolves we believe that the remaining nine mutational hotspots may contain variants that can emerge in the future. We believe that this may be promising in helping the research community to devise therapeutics based on probable new mutation zones in the viral sequence and resemblance in properties of various mutations.

Mullick|Baishali|B|
Magar|Rishikesh|R|
Jhunjhunwala|Aastha|A|
Barati Farimani|Amir|A|

Mutations
SARS-CoV-2
Shannon entropy
Clustering


Accelerated Fractionation With Concomitant Boost vs. Conventional Radio-chemotherapy for Definitive Treatment of Locally Advanced Squamous Cell Carcinoma of the Head-and-Neck (SCCHN).

Abstract:
BACKGROUND/AIM
Patients with unresectable head-and-neck cancer (SCCHN) unable to tolerate radiochemotherapy may receive unconventionally fractionated radiotherapy. This retrospective study compared both treatments.

PATIENTS AND METHODS
Eight patients unsuitable for chemotherapy were assigned to accelerated fractionation with concomitant boost (AF-CB, 69.6 Gy/39 fractions) over 5.5 weeks (group A) and 72 patients to cisplatin-based radiochemotherapy (70 Gy/35 fractions) over 7 weeks (group B). Groups were matched (cancer site, gender, age, performance score, T-/N-stage, histologic grade) and compared for loco-regional control (LRC), metastases-free survival (MFS), overall survival (OS) and toxicities.

RESULTS
LRC, MFS, OS and radiation-related toxicities were not significantly different between groups A and B. Improved outcomes were associated with favorable cancer site, better performance score and T3-stage. In group B, toxicity led to reduction/discontinuation of chemotherapy in 38.9% and interruptions of radiotherapy >7 days in 19.3% of patients.

CONCLUSION
AF-CB appeared a reasonable alternative for patients who cannot safely receive radio-chemotherapy for unresectable SCCHN.

Narvaez|Carlos A|CA|
Schild|Steven E|SE|
Janssen|Stefan|S|
Schroeder|Ursula|U|
Bruchhage|Karl L|KL|
Hakim|Samer G|SG|
Rades|Dirk|D|

D000077195:Squamous Cell Carcinoma of Head and Neck

accelerated fractionation
concomitant boost
conventional radio-chemotherapy
Locally advanced head-and-neck cancer
stage IV disease


Adsorption of ammonium on biochar prepared from giant reed.

Abstract: Giant reed was used as precursor for making biochar in order for the adsorption of NH4 (+)-N from aqueous solution. And the adsorption of the product to NH4 (+)-N was examined. The surface features of biochar were investigated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy/energy dispersive spectrometer (SEM-EDS), and X-ray diffraction (XRD). XRD patterns showed several peaks and correspond to the high amount of crystalline material. The crystals contain KCl, K2O, CaO, MgO, and SiO and possess high surface area which enhances adsorption. The influence of different parameters such as initial concentration, adsorption time, pH, and ionic strength has been carried out. The adsorption could reach equilibrium through 24 h reaction and had the best adsorption amount at the solution pH values from 7 to 9. The cation has great influence on the adsorption of NH4 (+)-N, whereas the anion exerted a weaker effect. The adsorption followed pseudo-first-order and pseudo-second-order models. And the intraparticle diffusion and desorption studies further elucidated that the mechanism of adsorption on the product was ion exchange. The product equilibrium data was well described by the Langmuir and Freundlich model. The maximum adsorption capacities were 1.490 mg/g. Biochar derived from giant reed at 500 °C was suggested as a promising adsorbent for the removal of NH4 (+)-N from slightly polluted wastewater.

Hou|Jie|J| Huang|Lei|L| Yang|Zhimin|Z| Zhao|Yaqi|Y| Deng|Chaoren|C| Chen|Yucheng|Y| Li|Xin|X|

D017550:Spectroscopy, Fourier Transform Infrared

Ammonium
Biochar
Giant reed
Adsorption experiments
Adsorption kinetics and isotherms


In vitro evaluation of photodynamic therapy using curcumin on Leishmania major and Leishmania braziliensis.

Abstract: Cutaneous leishmaniasis is an infectious disease caused by the Leishmania protozoan. The conventional treatment is long-lasting and aggressive, in addition to causing harmful effect. Photodynamic therapy has emerged as a promising alternative treatment, which allows local administration with fewer side effects. This study investigated the photodynamic activity of curcumin on Leishmania major and Leishmania braziliensis promastigote. Both species were submitted to incubation with curcumin in serial dilutions from 500 μg/ml up to 7.8 μg/ml. Control groups were kept in the dark while PDT groups received a fluency of 10 J/cm(2) at 450 nm. Mitochondrial activity was assessed by MTT assay 18 h after light treatment, and viability was measured by Trypan blue dye exclusion test. Morphological alterations were observed by Giemsa staining. Confocal microscopy showed the uptake of curcumin by both tested Leishmania species. Mitochondrial activity was inconclusive to determine viability; however, Trypan blue test was able to show that curcumin photodynamic treatment had a significant effect on viability of parasites. The morphology of promastigotes was highly affected by the photodynamic therapy. These results indicated that curcumin may be a promising alternative photosensitizer, because it presents no toxicity in the dark; however, further tests in co-culture with macrophages and other species of Leishmania should be conducted to determine better conditions before in vivo tests are performed.

Pinto|Juliana Guerra|JG|
Fontana|Letícia Correa|LC|
de Oliveira|Marco Antonio|MA|
Kurachi|Cristina|C|
Raniero|Leandro José|LJ|
Ferreira-Strixino|Juliana|J|

Photodynamic therapy
Curcumin
Leishmania major
Leishmania braziliensis
Cutaneous leishmaniasis


Molecular inferences about the genus Hypostomus Lacépède, 1803 (Siluriformes: Loricariidae): a review.

Abstract: This review compiles and discusses the use of genetic markers applied in the study of the fish genus Hypostomus Lacépède, 1803 (Siluriformes: Loricariidae). The database comprises 51 peer-review articles that were published in the last 52 years (1968-2020) and that approach analysis based on different classes of genetic markers. The use of cytogenetic and enzymatic markers was predominantly especially in population studies with the genus Hypostomus, while mitochondrial markers were the majority in phylogenetic studies. Although significant methodological advances have occurred for molecular evaluation, they are still modestly applied to the study of neotropical fish genera, in which Hypostomus is included. New perspectives, especially on integrative approaches, are needed to improve our knowledge of the genetic functionality of fishes.

Armored catfish
Karyotype
Phylogeny
SSR
mtDNA
rDNA


Hepatitis B virus biology and life cycle.

Abstract: Hepatitis B virus (HBV) specifically infects hepatocytes and causes severe liver diseases. The HBV life cycle is unique in that the genomic DNA (relaxed-circular partially double-stranded DNA: rcDNA) is converted to a molecular template DNA (covalently closed circular DNA: cccDNA) to amplify a viral RNA intermediate, which is then reverse-transcribed back to viral DNA. The highly stable characteristics of cccDNA result in chronic infection and a poor rate of cure. This complex life cycle of HBV offers a variety of targets to develop antiviral agents. We provide here an update on the current knowledge of HBV biology and its life cycle, which may help to identify new antiviral targets.

D000998:Antiviral Agents
D004279:DNA, Viral
D056945:Hep G2 Cells
D006509:Hepatitis B
D006515:Hepatitis B virus
D022781:Hepatocytes
D000076662:Host Microbial Interactions
D006801:Humans
D014779:Virus Replication

Life cycle
HBV
cccDNA
Entry
NTCP
Replication


The effects of display size on performance.

Abstract: We examined the systematic effects of display size on task performance as derived from a standard perceptual and cognitive test battery. Specifically, three experiments examined the influence of varying viewing conditions on response speed, response accuracy and subjective workload at four differing screen sizes under three different levels of time pressure. Results indicated a ubiquitous effect for time pressure on all facets of response while display size effects were contingent upon the nature of the viewing condition. Thus, performance decrement and workload elevation were evident only with the smallest display size under the two most restrictive levels of time pressure. This outcome generates a lower boundary threshold for display screen size for this order of task demand. Extrapolations to the design and implementation of all display sizes and forms of cognitive and psychomotor demand are considered.

Hancock|P A|PA|
Sawyer|B D|BD|
Stafford|S|S|

D000328:Adult
D016288:Computer Terminals
D004867:Equipment Design
D005260:Female
D064368:Healthy Volunteers
D006801:Humans
D008297:Male
D011897:Random Allocation
D011930:Reaction Time
D012737:Sex Factors
D015144:Southeastern United States
D013647:Task Performance and Analysis
D013997:Time Factors
D016526:Workload
D055815:Young Adult

display size
speed
accuracy
time pressure
response capacity


Encephalitis Associated With Hemophagocytic Lymphohistiocytosis Secondary to Immune Checkpoint Inhibitors: An Unfamiliar Spin-Off.

Abstract: Checkpoint inhibitors (CPI) have become mainstream in standard therapy in various tumors, especially in malignant melanoma. Despite their widespread beneficial effects, these inhibitors are also notorious for immune-related adverse events (irAEs). Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life-threatening syndrome of excessive immune activation. We report a case of a 33-year-old male having a history of metastatic melanoma on immunotherapy (status post two cycles of ipilimumab/nivolumab) admitted for persistent fever and elevated liver enzymes. Additional work showed anemia, thrombocytopenia, hypertriglyceridemia, and hyperferritinemia which meet the diagnostic criteria of histiocyte society HLH-2004. The patient was effectively treated with oral prednisone. Moreover, further complications encompassed slurred speech, word-finding difficulties, ataxia, and lower extremity hyperreflexia concerning for autoimmune encephalitis. He was treated with high-dose IV methylprednisolone (1 gram/day for 3 days) with improvement in symptoms. Autoimmune encephalitis associated with HLH can be fatal - high-dose IV methylprednisolone should be considered, but this avenue still needs to be explored.

Ghous|Ghulam|G|
Shoukat|Hafiz Muhammad Hassan|HMH|
Tarar|Zahid Ijaz|ZI|
Zafar|Muhammad Usman|MU|
McGreevy|Joseph W|JW|


Clinical relevance of deferasirox trough levels in β-thalassemia patients.

Abstract: We evaluated the role of deferasirox therapeutic drug monitoring in order to avoid toxicity or treatment failure. Plasma concentrations, measured between two consecutive liver iron determinations, were determined at the end of dosing interval. Fifty-four β-thalassemic adult patients were enrolled: 50% were males; median age was 32.3 years (IQR 19.1-41.7 years) and median body mass index was 22.25 kg/m2 (IQR 20.24-23.75 kg/m2 ). The mean deferasirox dose was 28.6 ± 6.3 mg/kg/d and mean plasma concentration was 17.3 ± 16.8 μg/mL. Drug levels showed lower results in males. Deferasirox concentration was significantly correlated with serum creatinine levels (P = .01) and serum ferritin (P < .0001). The assessment of deferasirox therapeutic drug monitoring could help clinicians to predict patient responses and to optimize the therapy.

Allegra|Sarah|S|0000-0003-4933-0011
Massano|Davide|D|
De Francia|Silvia|S|
Longo|Filomena|F|
Piccione|Francesca|F|
Pirro|Elisa|E|
Cusato|Jessica|J|
D'Avolio|Antonio|A|
Piga|Antonio|A|

β-thalassemia
therapeutic drug monitoring
creatinine
ferritin
iron overload


Biogas digestates affect crop P uptake and soil microbial community composition.

Abstract: Fermentation residues from biogas production are known as valuable organic fertilisers. This study deals with the effect of cattle slurry, co-digested cattle slurry, co-digested energy crops and mineral fertilisers on the activity and composition of soil microbiota. Furthermore, the effect of solid-liquid separation as a common pre-treatment of digestate was tested. The fertilising effects were analysed in an 8-week pot experiment on loamy sand using two crops, Amaranthus cruentus and Sorghum bicolor. Amaranth, as a crop with significantly higher P uptake, triggered stress for occurring soil microbes and thereby caused a reduction of microbial biomass C in the soil. Irrespective of the crop, microbial basal respiration and metabolic quotient were higher with the digestates than with the untreated slurry or the mineral treatments. Community level physiological profiles with MicroResp showed considerable differences among the treatments, with particularly strong effects of solid-liquid separation. Similar results were also found on a structural level (PCR-DGGE). Alkaline phosphatase gene analyses revealed high sensitivity to different fertilisation regimes.

Hupfauf|Sebastian|S|
Bachmann|Silvia|S|
Fernández-Delgado Juárez|Marina|M|
Insam|Heribert|H|
Eichler-Löbermann|Bettina|B|

Soil
ALPS
Biogas residues
CLPP
Phosphate solubilising bacteria
Phosphorus
Solid–liquid separation


Cancer treatment and survivorship statistics, 2016.

Abstract: The number of cancer survivors continues to increase because of both advances in early detection and treatment and the aging and growth of the population. For the public health community to better serve these survivors, the American Cancer Society and the National Cancer Institute collaborate to estimate the number of current and future cancer survivors using data from the Surveillance, Epidemiology, and End Results cancer registries. In addition, current treatment patterns for the most prevalent cancer types are presented based on information in the National Cancer Data Base and treatment-related side effects are briefly described. More than 15.5 million Americans with a history of cancer were alive on January 1, 2016, and this number is projected to reach more than 20 million by January 1, 2026. The 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), and melanoma (614,460) among males and breast (3,560,570), uterine corpus (757,190), and colon and rectum (727,350) among females. More than one-half (56%) of survivors were diagnosed within the past 10 years, and almost one-half (47%) are aged 70 years or older. People with a history of cancer have unique medical and psychosocial needs that require proactive assessment and management by primary care providers. Although there are a growing number of tools that can assist patients, caregivers, and clinicians in navigating the various phases of cancer survivorship, further evidence-based resources are needed to optimize care. CA Cancer J Clin 2016;66:271-289. © 2016 American Cancer Society.

Miller|Kimberly D|KD|
Siegel|Rebecca L|RL|
Lin|Chun Chieh|CC|
Mariotto|Angela B|AB|
Kramer|Joan L|JL|
Rowland|Julia H|JH|
Stein|Kevin D|KD|
Alteri|Rick|R|
Jemal|Ahmedin|A|

D054547:National Cancer Institute (U.S.)

survivorship
statistics
treatment patterns
prevalence


Y box binding protein 1 inhibition as a targeted therapy for ovarian cancer.

Abstract: Y box binding protein 1 (YB-1) is a multifunctional protein associated with tumor progression and the emergence of treatment resistance (TR). Here, we report an azopodophyllotoxin small molecule, SU056, that potently inhibits tumor growth and progression via YB-1 inhibition. This YB-1 inhibitor inhibits cell proliferation, resistance to apoptosis in ovarian cancer (OC) cells, and arrests in the G1 phase. Inhibitor treatment leads to enrichment of proteins associated with apoptosis and RNA degradation pathways while downregulating spliceosome pathway. In vivo, SU056 independently restrains OC progression and exerts a synergistic effect with paclitaxel to further reduce disease progression with no observable liver toxicity. Moreover, in vitro mechanistic studies showed delayed disease progression via inhibition of drug efflux and multidrug resistance 1, and significantly lower neurotoxicity as compared with etoposide. These data suggest that YB-1 inhibition may be an effective strategy to reduce OC progression, antagonize TR, and decrease patient mortality.

Tailor|Dhanir|D|
Resendez|Angel|A|
Garcia-Marques|Fernando Jose|FJ|
Pandrala|Mallesh|M|
Going|Catherine C|CC|
Bermudez|Abel|A|
Kumar|Vineet|V|
Rafat|Marjan|M|
Nambiar|Dhanya K|DK|
Honkala|Alexander|A|
Le|Quynh-Thu|QT|
Sledge|George W|GW|
Graves|Edward|E|
Pitteri|Sharon J|SJ|
Malhotra|Sanjay V|SV|

Y box binding protein 1
targeted therapy
ovarian cancer
treatment resistance


The Role of Laboratory Medicine in Addressing Migrant Health Problems.

Abstract:
Introduction
A migrant is a person who has relocated to another country for varying reasons. Laboratory medicine is a medical speciality in which body specimens are examined and results interpreted for the appropriate management of patients in healthy and diseased states.

Health challenges of migrants
Migrants have health problems like the general population but may be affected by factors such as their geographic origin, living conditions, and their physical and psychological conditions.

The role of laboratory medicine
Laboratory medicine will play a vital role in the provision of quality healthcare services to migrants. It will be actively involved in the screening, diagnosis, and monitoring of response to treatment. Effective public health surveillance among migrants will require laboratory services. The data gathered from research using laboratory resources will help in the improvement of the quality of migrant health.

laboratory medicine
migrant
health issues


C/EBP-α, involvement of a novel transcription factor in leptin-induced VCAM-1 production in mouse chondrocytes.

Abstract: Leptin and vascular cell adhesion molecules-1 (VCAM-1) are two important mediators in obesity-related osteoarthritis, while the molecular mechanism linking leptin to VCAM-1 production is still obscure. Here we show that leptin upregulates VCAM-1 mRNA and protein levels in a time- and dose-dependent manner. Mechanistically, leptin induces VCAM-1 promoter activity by increasing the expression of C/EBP-α and facilitating its binding to a newly identified element in the VCAM-1 gene. Gain or loss of function studies reveal a regulatory role of C/EBP-α on VCAM-1 expression. Finally, elevated plasma leptin level correlates to increased C/EBP-α and VCAM-1 production in chondrocytes from obese mice.

Kang|Xia|X| Xie|Qing-Yun|QY| Zhou|Jing-Song|JS| Zhang|Bo|B| Liao|Dong-Fa|DF| Wu|Hong-Hua|HH| Zheng|Wei|W| Pan|Xian-Ming|XM| Quan|Yi|Y|

D019010:Vascular Cell Adhesion Molecule-1


The horizontal computerized rotational impulse test.

Abstract: Whole-body impulsive rotations were used to overcome several limitations associated with manual head impulse testing. A computer-controlled rotational chair delivered brief, whole-body, earth-vertical axis yaw impulsive rotations while eye movements were measured using video-oculography. Results from an unselected group of 20 patients with dizziness and a group of 22 control subjects indicated that the horizontal computerized rotational head impulse test (crHIT) is well-tolerated and provides an estimate of unidirectional vestibulo-ocular reflex gain comparable to results from caloric testing. This study demonstrates that the horizontal crHIT is a new assessment tool that overcomes many of the limitations of manual head impulse testing and provides a reliable laboratory-based measure of unilateral horizontal semicircular canal function.

Furman|Joseph M|JM|
Shirey|Ian|I|
Roxberg|Jillyn|J|
Kiderman|Alexander|A|

head impulse testing
Vestibulo-ocular reflex
semicircular canal


Chemical preparation of graphene materials results in extensive unintentional doping with heteroatoms and metals.

Abstract: Chemical synthesis of graphene relies on the usage of various chemical reagents. The initial synthesis step, in which graphite is oxidized to graphite oxide, is achieved by a combination of chemical oxidants and acids. A subsequent chemical reduction step eliminates/reduces most oxygen functionalities to yield graphene. We demonstrate here that these chemical treatments significantly contaminate graphene with heteroatoms/metals, depending on the procedures followed. Contaminations with heteroatoms (N, B, Cl, S) or metals (Mn, Al) were present at relatively high concentrations (up to 3 at%), with their chemical states dependent on the procedures. Such unintentional contaminations (unwanted doping) during chemical synthesis are rarely anticipated and reported, although the heteroatoms/metals may alter the electronic and catalytic properties of graphene. In fact, the levels of unintentionally introduced contaminants on graphene are often higher than typical levels found on intentionally doped graphene. Our findings are important for scientists applying chemical methods to prepare graphene.

Chua|Chun Kiang|CK|
Ambrosi|Adriano|A|
Sofer|Zdeněk|Z|
Macková|Anna|A|
Havránek|Vladimír|V|
Tomandl|Ivo|I|
Pumera|Martin|M|

graphene
doping
heteroatoms
oxidation
synthetic methods


Reflectance and imaging spectroscopy applied to detection of petroleum hydrocarbon pollution in bare soils.

Abstract: Accidental releases of hazardous waste related to the extraction, refining, and transport of oil and gas are inevitable. Petroleum facilities and intrinsic pipelines present environmental pollution risks, threatening both human health and ecosystems. Research has been undertaken to enhance the conventional methods for monitoring hazardous waste problems and to improve time-consuming and cost-effective ways for leak detection and remediation process. In this study, both diffuse and imaging (hyperspectral) reflectance spectroscopy are used for detection and characterization of petroleum hydrocarbon (PHC) contamination in latosols. Laboratory and field measurements of PHC-contaminated and PHC-free soils were collected from an oil facility using an ASD FieldSpec-3 high-resolution portable spectrometer (2150 channels) covering visible, near infrared and shortwave infrared wavelengths (VNIR-SWIR: 350-2500 nm). The hyperspectral image dataset was acquired with the ProSpecTIR-VS airborne sensor using 357 channels in the VNIR-SWIR range at 1 m of spatial resolution. Narrow intervals of reflectance spectra were analyzed to identify the primary mineral and PHC absorption bands in soil samples and to investigate the spectral match with airborne hyperspectral data. The Multiple Endmember Spectral Mixture Analysis (MESMA) method was employed in three hierarchical levels to classify the hyperspectral imagery. The classification product yielded from MESMA model at the fourth level was 98% accurate in discriminating contaminated soils. The results demonstrated the applicability of both diffuse reflectance and imaging (hyperspectral) spectroscopy to identify bare soils contaminated by PHC leaks and spills. These technologies can also provide useful information for remediation initiatives, thereby avoiding further problems with hazardous waste.

Correa Pabón|Rosa Elvira|RE|
Souza Filho|Carlos Roberto de|CR|
Oliveira|Wilson José de|WJ|

Imaging spectroscopy
Petroleum
Hydrocarbon
Contamination
Diffuse reflectance spectroscopy
MESMA method


Endoscopic treatment of symptomatic fibroids at reproductive age and beyond.

Abstract:
OBJECTIVES
To evaluate the feasibility of endoscopic treatment of symptomatic uterine fibroids based on patient and fibroid characteristics in reproductive, pre-menopausal and post-menopausal women.

MATERIAL AND METHODS
The medical records of women with symptomatic uterine fibroids who underwent surgical procedures from 2010 to 2015 were retrospectively reviewed.

RESULTS
A total of 819 patients, of which 710 (86.6%) underwent endoscopic procedures. The mean age of women who underwent laparoscopic myomectomy (LM) was 36.77 ± 6.54 and hysteroscopic myomectomy (HSCM) was 43.10 ± 10.26. The mean cumulative diameter of fibroids in the LM was 8.94 ± 3.1 and 3.68 ± 1.64 cm in the HSCM. Furthermore, LM and HCSM were performed when the mean diameter of the largest fibroid was up to 18.50 and 5.5 cm, respectively. The mean age of women in laparoscopic supracervical hysterectomy (LSH) was 46.02 ± 6.13 and total laparoscopic hysterectomy (TLH) was 47.30 ± 8.12. The mean cumulative diameter of fibroids in the LSH was greater than in the TLH, at 8.94 ± 3.1 and 7.63 ± 3.60 cm, respectively.

CONCLUSIONS
Uterus-preserving procedures are feasible, even if the largest fibroid diameter is more than 10 cm in LM and equal to 5.5 cm in HSCM. For pre- and post-menopausal women, TLH is the definitive treatment modality for uterine fibroids, and LSH represents an alternative to TLH.

Abdusattarova|Khulkar|K| Mettler|Liselotte|L| Alkatout|Ibrahim|I| Dempfle|Astrid|A|

Uterine fibroids
laparoscopic myomectomy
laparoscopic hysterectomy
hysteroscopy


Self-reported balance status is not a reliable indicator of balance performance in adolescents at one-month post-concussion.

Abstract:
OBJECTIVES
To determine if self-reported balance symptoms can be used as a proxy for measures of the center of pressure (COP) to identify balance deficits in a group of concussed adolescents.

DESIGN
Case-control.

METHODS
Thirteen adolescents 1-month post-concussion who reported ongoing balance problems (Balance+), 20 adolescent 1-month post-concussion who reported no balance problems (Balance-), and 30 non-injured adolescents (control) completed a series of balance tests. Participants completed two 2-min trials standing on a Nintendo Wii Balance Board™ during which the COP under their feet was recorded: i) double-leg stance, eyes open; ii) double-leg stance, eyes closed. Participants also completed a dual-task condition combining a double-leg stance and a Stroop Colour-word test.

RESULTS
Participants in both the Balance+ and Balance- group swayed over a larger ellipse area compared to the control group while completing the Eyes Closed (Balance+, p=0.002; Balance-, p=0.002) and Dual-Task (Balance+, p=0.001; Balance-, p=0.004) conditions and performed the Dual-Task condition with faster medio-lateral velocity (Balance+, p=0.003; Balance-, p=0.009). The participants in the Balance- group also swayed over a larger ellipse area compared to the control group while completing the Eyes Open condition (p=0.005). No significant differences were identified between the Balance+ and Balance- groups.

CONCLUSIONS
At 1-month post-concussion, adolescents demonstrated balance deficits compared to non-injured adolescents regardless of whether they reported balance problems. These results suggest that self-reported balance status might not be an accurate reflection of balance performance following a concussion in adolescents.

Rochefort|Coralie|C| Walters-Stewart|Coren|C| Aglipay|Mary|M| Barrowman|Nick|N| Zemek|Roger|R| Sveistrup|Heidi|H|

Adolescent
Brain injury
Cognitive function
Injury management
Postural balance


MMP-9 inhibition facilitates amacrine cell loss after ouabain-induced retinal damage.

Abstract: Retinal ischemia is a common risk factor for visual impairment and blindness. Two common changes after retinal ischemia are retinal ganglion cell (RGC) loss and Müller glial cell (MGC)-mediated endogenous repair. Matrix metalloproteinase 9 (MMP-9) has been shown to be responsible to RGC death. However, the effects of MMP-9 on the loss of other neurons and the reactivity of MGCs after retinal injury remain unclear. Ouabain, a Na/K-ATPase inhibitor, was injected into the vitreous body of rat eyes to induce cell death in the inner nuclear layer (INL). MMP-9 expression and activation in the retinas were examined by gelatin zymography and immunohistochemistry. The role of MMP-9 inhibitor (MMP-9i) in ouabain-treated retinas was assessed. After ouabain injection, there was an upregulation of MMP-9 activity in the inner retinas, and the activation of MMP-9 reached a maximum at 2 day. Unexpectedly, MMP-9i enhanced the thinning of the INL, the loss of Calbindin D-28k-positive cells and Syntaxin-positive amacrine cells (ACs) in the INL and decreased levels of Calbindin D-28k protein, while leaving the outer nuclear layer (ONL) unchanged. In addition, MMP-9i led to a minor increase in the number of BrdU positive cells that did not express GS in the INL. Collectively, these results revealed that the inhibition of MMP-9 activity facilitated AC loss and promoted the generation of MGC-derived cells in ouabain-treated retinas, which indicates that treating retinal diseases with drugs that inhibit MMP-9 activity should be considered with caution.

MMP-9
Amacrine cell
Retinal ischemia
Müller glial cell
Ouabain


Accuracy of the ECG for differential diagnosis between hypertrophic cardiomyopathy and athlete's heart: comparison between the European Society of Cardiology (2010) and International (2017) criteria.

Abstract:
BACKGROUND
Interpretation of the athlete's ECG is based on differentiation between benign ECG changes and potentially pathological abnormalities. The aim of the study was to compare the 2010 European Society of Cardiology (ESC) and the 2017 International criteria for differential diagnosis between hypertrophic cardiomyopathy (HCM) and athlete's heart.

METHODS
The study populations included 200 patients with HCM and 563 athletes grouped as follows: 'group 1', including normal ECG and isolated increase of QRS voltages, which are considered non-pathologic according to ESC and International criteria; 'group 2', including left atrial enlargement or left axis deviation in isolation and Q-waves with an amplitude ≥4 mm but <25% of the ensuing R-wave and a duration <0.04 s which are considered pathologic according to the ESC but not according to the International criteria; and 'group 3', including abnormalities which are considered pathologic according to ESC and International criteria.

RESULTS
Overall, the 2010 ESC criteria showed a sensitivity of 95.5% and a specificity of 86.9%. Considering group 2 ECG changes as normal according to the International criteria led to a statistically significant (p<0.001) increase of specificity to 95.9%, associated with a non-significant (p=0.47) reduction of sensitivity to 93%. Among patients with HCM, there was a significant increase of maximal left ventricular wall thickness from group 1 to 3 (p=0.02).

CONCLUSIONS
The use of 2017 International criteria is associated with a substantial increase in specificity and a marginal decrease in sensitivity for differential diagnosis between HCM and athlete's heart.

Zorzi|Alessandro|A| Calore|Chiara|C| Vio|Riccardo|R| Pelliccia|Antonio|A| Corrado|Domenico|D|

Hypertrophic cardiomyopathy
athlete’s heart
electrocardiogram
screening.


Enhancing the Performance of Stretchable Conductors for E-Textiles by Controlled Ink Permeation.

Abstract: Delivery of electronic functionality to the human body using e-textiles is important for realizing the future of wearable electronics. Printing is a promising process for large scale manufacturing of e-textile since it enables arbitrary patterns using a simple and inexpensive process. However, conductive inks printed atop of textile are vulnerable to cracking because of the deformable and porous structure of textiles. The authors develop a mechanically and electrically robust wiring by controlling ink permeation in the structure of textile. This is done by adjusting the ink's solvent. The use of butyl carbitol acetate, with its low vapor pressure and boiling point, enables deep permeation into the textile. The sheet resistance is initially 0.06 Ω sq-1 , and the resistance increasing only 70 times after stretching to 450% strain. Finally, a four-channel electromyogram (EMG) monitoring garment is demonstrated to show the potential of a large-scale e-textile device for health care and sports.

Jin|Hanbit|H| Matsuhisa|Naoji|N| Lee|Sungwon|S| Abbas|Mohammad|M| Yokota|Tomoyuki|T| Someya|Takao|T|

stretchable conductors
e-textile
biometric devices
composite materials
printed electronics


Distribution of the creatine transporter throughout the human brain reveals a spectrum of creatine transporter immunoreactivity.

Abstract: Creatine is a molecule that supports energy metabolism in cells. It is carried across the plasma membrane by the creatine transporter. There has been recent interest in creatine for its neuroprotective effects in neurodegenerative diseases and its potential as a therapeutic agent. This study represents the first systematic investigation of the distribution of the creatine transporter in the human brain. We have used immunohistochemical techniques to map out its location and the intensity of staining. The transporter was found to be strongly expressed, especially in the large projection neurons of the brain and spinal cord. These include the pyramidal neurons in the cerebral cortex, Purkinje cells in the cerebellar cortex, and motor neurons of the somatic motor and visceromotor cranial nerve nuclei and the ventral horn of the spinal cord. Many other neurons in the brain also had some degree of creatine transporter immunoreactivity. By contrast, the medium spiny neurons of the striatum and the catecholaminergic neurons of the substantia nigra and locus coeruleus, which are implicated in neurodegenerative diseases, showed a very low to almost absent level of immunoreactivity for the transporter. We propose that the distribution may reflect the energy consumption by different cell types and that the extent of creatine transporter expression is proportional to the cell's energy requirements. Furthermore, the distribution indicates that supplemented creatine would be widely taken up by brain cells, although possibly less by those cells that degenerate in Huntington's and Parkinson's diseases.

Lowe|Matthew T J|MT|
Faull|Richard L M|RL|
Christie|David L|DL|
Waldvogel|Henry J|HJ|


Effect of pectins on the mass transfer kinetics of monosaccharides, amino acids, and a corn oil-in-water emulsion in a Franz diffusion cell.

Abstract: The effect of high (HMP) and low (LMP) methoxylated pectins (2%w/w) on the rate and extent of the mass transfer of monosaccharides, amino acids, and a corn oil-in-water emulsion across a cellulose membrane was evaluated. A sigmoidal response kinetic analysis was used to calculate both the diffusion coefficients (rate) and the amount of nutrients transferred through the membrane (extent). In all cases, except for lysine, HMP was more effective than LMP in inhibiting both the rate and extent of the mass transfer of nutrients through the membrane. LMP and HMP, e.g., reduced 1.3 and 3.0times, respectively, the mass transfer rate of glucose, as compared to control (containing no pectin), and 1.3 and 1.5times, respectively, the amount of glucose transferred through the membrane. Viscosity, molecular interactions, and flocculation were the most important parameters controlling the mass transfer of electrically neutral nutrients, electrically charged nutrients, and emulsified lipids, respectively.

Pectin
Franz diffusion cell
Diffusion
Viscosity
Methoxylation degree


Epigallocatechin gallate improves insulin resistance in HepG2 cells through alleviating inflammation and lipotoxicity.

Abstract:
AIMS
High levels of circulating free fatty acids (FFAs), inflammation and oxidative stress are important causes for insulin resistance (IR) and type 2 diabetes mellitus. The aim of this study was to investigate the mechanisms of EGCG in alleviating IR in HepG2 cells.

METHODS
HepG2 cells were treated with 25 mM glucose, 0.25 mM palmitic acid (PA), or 50 μM EGCG for 24 h.

RESULTS
EGCG increased glucose uptake and decreased glucose content. EGCG markedly decreased the levels of inflammatory and oxidative stress factors including nuclear factor κB (NF-κB), tumor necrosis factor-α, interleukin-6, reactive oxygen species, malondialdehyde and p53 protein, and markedly increased superoxide dismutases (SOD), glutathione peroxidase and SOD2 protein. EGCG significantly downregulated the levels of FFAs, triacylglycerol and cholesterol in HepG2 cells. The glucose transporter 2 (GLUT2) protein and its downstream proteins peroxisome proliferator-activated receptor γ coactivator (PGC)-1β were significantly increased, and sterol regulatory element-binding-1c (SREBP-1c) protein, and fatty acid synthase (FAS) were significantly decreased by EGCG in HepG2. Moreover, the foregoing effects were reversed by siRNA-mediated knockdown of GLUT2.

CONCLUSION
Our data demonstrated that EGCG improved IR, possibly through ameliorating glucose (25 mM) and PA (0.25 mM)-induced inflammation, oxidative stress, and FFAs via the GLUT2/PGC-1β/SREBP-1c/FAS pathway in HepG2 cells.

Zhang|Qiao|Q| Yuan|Hang|H| Zhang|Cong|C| Guan|Yue|Y| Wu|Yuqing|Y| Ling|Fan|F| Niu|Yucun|Y| Li|Ying|Y|

Insulin resistance
Inflammation
Free fatty acids
Oxidative stress
EGCG


Preoperative cholangitis is an independent risk factor for mortality in patients after pancreatoduodenectomy for pancreatic cancer.

Abstract:
OBJECTIVES
Preoperative biliary stenting is required for patients with obstructive jaundice from pancreatic adenocarcinoma who are receiving neoadjuvant chemotherapy. While in most patients this approach results in durable biliary drainage, some patients develop cholangitis during neoadjuvant treatment. Further, several studies have shown that preoperative cholangitis in patients with hepatobiliary malignancies can result in substantially unfavorable outcomes. The aim of this study was to evaluate the impact of preoperative cholangitis in patients who underwent pancreaticoduodenectomy after completing neoadjuvant chemotherapy.

METHODS
Participants: all adult patients (n = 449) diagnosed with pancreatic adenocarcinoma from January 1st, 2013 to March 31st, 2018 who pursued treatment at the Massachusetts General Hospital were screened. Of these 449 patients, 97 met final inclusion criteria of receiving neoadjuvant chemotherapy with intent to pursue curative surgery. Data were collected via retrospective chart review including baseline characteristics, survival, episodes of preoperative cholangitis, and surgical complications.

RESULTS
In patients completing successful pancreaticoduodenectomy surgery, preoperative cholangitis is associated with increased mortality (HR 2.67, 95% CI:1.16-6.13). This finding is independent of postoperative outcomes or tumor recurrence rate. The presence of cholangitis did not impact completion of neoadjuvant chemotherapy (92% vs 85%, p = 0.5) or ability to proceed to surgery (76% vs 75%, p = 1.0). Preoperative cholangitis was not associated with postoperative morbidity (42.1% vs 45.1%, p = 1.0).

CONCLUSIONS
One episode of cholangitis during neoadjuvant chemotherapy is associated with increased mortality following successful pancreaticoduodenectomy, independent of immediate postoperative outcomes or tumor recurrence. Preoperative cholangitis does not affect ability to pursue neoadjuvant chemotherapy or complete successful surgery. Patients who develop cholangitis during the neoadjuvant chemotherapy treatment phase may reflect a distinct phenotype of patients with PDAC with a complex and more challenging clinical course.

Darnell|Eli P|EP|
Wang|Thomas J|TJ|
Lumish|Melissa A|MA|
Hernandez-Barco|Yasmin G|YG|
Weniger|Maximilian|M|
Casey|Brenna W|BW|
Qadan|Motaz|M|
Lillemoe|Keith D|KD|
Ferrone|Cristina R|CR|
Fernandez-Del Castillo|C|C|
Krishnan|Kumar|K|

Cholangitis Biliary Stenting ERCP Whipple


A Rare Case of Cannabis-induced Acute Pancreatitis.

Abstract: Acute pancreatitis is a sudden inflammatory condition of the pancreas, caused mainly by gallstones and alcohol abuse. A significant proportion of acute pancreatitis cases remain idiopathic. Recent reports have highlighted cannabis use as an etiology of acute pancreatitis. A few case reports are available that report the association of cannabis with acute pancreatitis. Considering the global use of cannabis medically and illicitly, it becomes imperative to explore this adverse effect of cannabis use especially in idiopathic cases of acute pancreatitis. Here, in this report, we present a case of acute pancreatitis with no obvious cause. The patient was a 48-year-old female with no history of alcohol use. She had a history of cholecystectomy with normal serum triglycerides and calcium levels. The patient was consuming marijuana (cannabis) daily for the last three years. The diagnosis of cannabis-induced acute pancreatitis was made in the patient after other causes were excluded. It is difficult to distinguish cannabis-induced pancreatitis as there are no clear and specific associated clinical features. The diagnosis of cannabis-induced pancreatitis becomes even more challenging due to the use of multiple drugs. It becomes difficult to point out the causative agent among the multitude of drugs. Hence, a detailed history of drug intake in cases of acute pancreatitis may help to identify the candidature of the drugs in the pathogenesis of the disease. In view of the increasing illicit and medical use of cannabis, it becomes quintessential for clinicians to consider pancreatitis as a possible adverse effect of cannabis.

Ghazaleh|Sami|S|
Alqahtani|Ali|A|
Nehme|Christian|C|
Abugharbyeh|Aya|A|
Said Ahmed|Tamer S|TS|


Supply chain redesign implications to information disruption impact.

Abstract: Over the years, supply chain reconfiguration decisions have been solely based on operational risk. Simplification strategies, such as horizontal mergers, and networking strategies, such as risk pooling, are conflicting paradigms that have been shown to improve financial performance of supply partners. The implication of this to disruption risk is not fully known, especially as it concerns information security breach (ISB). Analysts have rated ISB as a huge disruption risk, costing businesses millions of dollars. Using a credible and well-established agent-based simulation approach and statistical analysis, we examine the impact of ISB on the simplification and risk pooling strategies respectively under three different order replenishment systems. The effect of reconfiguring the supply chain is first examined in a non-security breach scenario and then in a breached scenario. We find that reconfiguration has no benefit to a supply chain using a parameter based replenishment policy (option I), in both breach and non-breach situations, but leads to significant advantage when batch ordering model (option II) or a combined batch-and-parameter based ordering policy (option III) is used. We also established that batch ordering system favours the risk pooling strategy whereas a combined batch-and-parameter ordering system favours the simplification counterpart especially when the simplification is at the wholesaler tier. This study has significant implications for supply chain design as well as information security priorities. This is one of the first papers to look at how ISB impacts supply chain configuration and the role of ordering decision context.

Durowoju|Olatunde A|OA|
Chan|Hing Kai|HK|
Wang|Xiaojun|X|
Akenroye|Temidayo|T|

Disruption impact
Information security breach
Simulation
Supply chain design
Inventory management


Condylar orientation plating in comminuted intraarticular fractures of adult distal humerus.

Abstract:
BACKGROUND
The condyles of the distal humerus have characteristic orientation in reference to the diaphysis. Anatomical reduction of the articular surface in intraarticular fractures of adult distal humerus does not always restore preinjury functional status. The purpose of this study was to determine the outcome of treating these fractures with technique of condylar orientation precontoured plating. The principle of the technique is to primarily restore the anatomical orientation of the reconstructed distal humeral condyle with the diaphysis of the humerus apart from anatomical reduction of fracture.

MATERIALS AND METHODS
Seventy one consecutive patients with comminuted intraarticular adult distal humerus fractures were treated with the condylar orientation plates, which were specifically designed between 1999 and 2009. 43 fractures were Association for osteosynthesis (AO) type C3, 24 were C2 and 4 were C1. Six were open cases and two were of nonunion distal end humerus. On medial and posterolateral side of the distal humerus, precontoured Sherman plates were applied. Patients were followed up for a mean of 3 years. They were assessed clinically (using mayo elbow performance score [MEPS]) and radio-graphically.

RESULTS
Sixty (84.5%) patients regained MEPS of 90 or more that is an excellent result (range of movement and functional status). One patient had nonunion with implant failure, and two patients developed heterotopic ossification. The mean MEPS was 95. Average extension and flexion was 15° and 133°. The result was graded as excellent in 60, good in 7, fair in 3 and poor in 1. At the time of most recent followup, 63 elbows were painless, and eight had mild pain.

CONCLUSION
Excellent pain free range of motion with a high rate of union can be achieved in comminuted intraarticular distal humerus fractures in adults with the use of condylar orientation precontoured plating technique. Condylar orientation is very important with perfect articular congruity in elbow motion.

intraarticular fracture
fractures
distal humerus
humerus
precontoured plating
Bone
Comminuted fracture
bone plates
fracture fixation
humeral condylar fracture


Inducing enantioselective crystallization with and self-assembly of star-shaped hybrid polymers prepared via "grafting to" strategy.

Abstract: Helical polymers present some interesting and distinctive properties, and one of the most distinguished applications of them is the chiral recognition and resolution of enantiomers. In this work, star-shaped hybrid helical poly (phenyl isocyanide) (PPI) with polyhedral oligomeric silsesquioxanes (POSS) as the core was designed and synthesized by "grafting to" strategy. The homoarm star-shaped hybrid POSS-(PPI)8 was first obtained by the click reaction between azide-modified POSS (POSS-(N3 )8 ) and alkynyl-modified PPI (PPI-Alkynyl). The hybrid POSS-(PPI)8 was with predominated left-handed helical conformation and exhibited excellent ability in the enantioselective crystallization of racemic compounds. In the meantime, heteroarm star-shaped hybrid (PEG)4 -POSS-(PPI)4 was prepared by the click reaction of POSS-(N3 )8 with PPI-Alkynyl and alkynyl-modified poly (ethylene glycol) (PEG-Alkynyl). The hybrid (PEG)4 -POSS-(PPI)4 was amphiphilic, and it could self-assemble to form spherical micelles in aqueous solutions.

enantioselective crystallization
self-assembly
helical polymer
poly (phenyl isocyanide)
POSS
star polymer


Predictive value of induced hyperammonaemia and neuropsychiatric profiling in relation to the occurrence of post-TIPS hepatic encephalopathy.

Abstract: Hepatic encephalopathy (HE) occurs in 20-50% of patients after transjugular intrahepatic portosystemic shunt (TIPS) placement. Older age, HE history and severe liver failure have all been associated with post-TIPS HE but it remains difficult to identify patients at risk. The aim of the present pathophysiological, pilot study was to assess the role of induced hyperammonaemia and associated neuropsychological and neurophysiological changes as predictors of post-TIPS HE. Eighteen TIPS candidates with no overt HE history (56 ± 8 yrs., MELD 11 ± 3) underwent neurophysiological [Electroencephalography (EEG)], neuropsychological [Psychometric Hepatic Encephalopathy Score (PHES) and Scan tests], ammonia and sleepiness assessment at baseline and after the induction of hyperammonaemia by an oral amino acid challenge (AAC). Pre-AAC, 17% of patients had abnormal EEG, 5% abnormal PHES, and 33% abnormal Scan performance. Post-AAC, 17% had abnormal EEG, 0% abnormal PHES, and 17% abnormal Scan performance. Pre-AAC, ammonia concentrations were 201 ± 73 μg/dL and subjective sleepiness 2.5 ± 1.2 (1-9 scale). Post-AAC, patients exhibited the expected increase in ammonia/sleepiness. Six months post-TIPS, 3 patients developed an episode of HE requiring hospitalization; these showed significantly lower pre-AAC fasting ammonia concentrations compared to patients who did not develop HE (117 ± 63 vs. 227 ± 57 μg/dL p = 0.015). They also showed worse PHES/Scan performance pre-AAC, and worse Scan performance post-AAC. Findings at 12 months follow-up (n = 5 HE episodes) were comparable. In conclusion, baseline ammonia levels and both pre- and post-AAC neuropsychiatric indices hold promise in defining HE risk in TIPS candidates with no HE history.

Senzolo|Marco|M| Zarantonello|Lisa|L| Formentin|Chiara|C| Orlando|Costanza|C| Beltrame|Raffaello|R| Vuerich|Anna|A| Angeli|Paolo|P| Burra|Patrizia|P| Montagnese|Sara|S|0000-0003-2800-9923

D019168:Portasystemic Shunt, Transjugular Intrahepatic

Ammonia
Oral amino acid challenge
Cirrhosis
Prognosis


Language Experience with a Native-Language Phoneme Sequence Modulates the Effects of Attention on Cortical Sensory Processing.

Abstract: Auditory evoked potentials (AEP) reflect spectro-temporal feature changes within the spoken word and are sufficiently reliable to probe deficits in auditory processing. The current research assessed whether attentional modulation would alter the morphology of these AEPs and whether native-language experience with phoneme sequences would influence the effects of attention. Native-English and native-Polish adults listened to nonsense word pairs that contained the phoneme sequence onsets /st/, /sət/, /pət/ that occur in both the Polish and English languages and the phoneme sequence onset /pt/ that occurs in the Polish language, but not the English language. Participants listened to word pairs within two experimental conditions designed to modulate attention. In one condition, participants listened to word pairs and performed a behavioral task to the second word in the pairs ("with task") and in the alternate condition participants listened to word pairs without performing a task ("without task"). Conditions were counterbalanced so that half the English and Polish subjects performed the "without task" condition as the first testing session and the "with task" condition as the second testing session. The remaining English and Polish subjects performed the tasks in the reverse order. Two or more months separated the testing sessions. Task conditions did not modulate the morphology of the AEP. Attention, however, modulated the AEP by producing a negative shift in the overall waveform. This effect of attention was modulated by experience with a native-language phoneme sequence. Thus, only Polish listeners showed an effect of attention to the native language /pt/ onset when the behavioral task occurred as the second testing session for which attention demands were reduced. This effect began at 400 ms and suggests a mechanism at intermediate stages within auditory cortex that facilitates recognition of the native language for comprehension.

Wagner|Monica|M|
Lee|Jungmee|J|
Mingino|Francesca|F|
O'Brien|Colleen|C|
Constantine|Adam|A|
Shafer|Valerie L|VL|
Steinschneider|Mitchell|M|

native-language
attention
auditory evoked potential (AEP)
spectro-temporal features
P1-N1-P2
T-complex


Relationship between corneal biomechanical parameters and corneal sublayer thickness measured by Corvis ST and UHR-OCT in keratoconus and normal eyes.

Abstract:
BACKGROUND
To explore the relationship between corneal biomechanical parameters and corneal sublayer thickness using corneal visualization Scheimpflug technology (Corvis ST) and ultrahigh-resolution optical coherence tomography (UHR-OCT) in clinical and suspected keratoconus and normal eyes.

METHODS
Cross-sectional prospective study. A total of 94 eyes of 70 participants were recruited. Twenty five eyes of 19 keratoconus patients, 52 eyes of 34 patients showing high risk of developing keratoconus according to the Belin/Ambrosio Enhanced Ectasia Display, and each eye of 17 normal subjects were enrolled. All participants underwent Corvis ST, Pentacam, and UHR-OCT examinations at the same time. Stiffness parameter A1 (SP-A1), deformation amplitude ratio (DA ratio), and other biomechanical parameters were recorded using Corvis ST. The vertical and horizontal thickness profiles of central 3 mm corneal epithelium, Bowman's layer, and stroma as measured by the perpendicular distance between the neighboring interfaces were generated using UHR-OCT. The flat keratometry and steep keratometry were obtained using Pentacam. Analysis of correlation was applied to explore the association between variables.

RESULTS
Most of the biomechanical parameters and corneal sublayer thickness profiles showed statistical differences among three groups. A statistically significant linear relationship was noted between SP-A1 and DA ratio in all three groups. SP-A1 was found to be positively correlated with epithelial and Bowman's layer thickness in the keratoconus (KC) group, and with stromal thickness in all three groups. In the normal and suspected keratoconus (SKC) groups, only stromal thickness was included in the stepwise linear regression to predict SP-A1, whereas in the KC group, steep keratometry and Bowman's layer thickness were included.

CONCLUSIONS
Significant and different correlations were noted between corneal stiffness and corneal sublayer thickness in different groups, indicating that corneal sublayers may play different roles in maintaining corneal biomechanical stability between keratoconus and normal eyes.

Li|Yong|Y| Xu|Zhiqiang|Z| Liu|Qiaoli|Q| Wang|Yuzhou|Y| Lin|Kan|K| Xia|Jiahui|J| Chen|Shihao|S| Hu|Liang|L|

Biomechanics
Corvis ST
UHR-OCT
Keratoconus
Corneal thickness


Unraveling the MAX2 Protein Network in Arabidopsis thaliana: Identification of the Protein Phosphatase PAPP5 as a Novel MAX2 Interactor.

Abstract: The F-box protein MORE AXILLARY GROWTH 2 (MAX2) is a central component in the signaling cascade of strigolactones (SLs) as well as of the smoke-derived karrikins (KARs) and the so far unknown endogenous KAI2 ligand (KL). The two groups of molecules are involved in overlapping and unique developmental processes, and signal-specific outcomes are attributed to perception by the paralogous α/β-hydrolases DWARF14 (D14) for SL and KARRIKIN INSENSITIVE 2/HYPOSENSITIVE TO LIGHT (KAI2/HTL) for KAR/KL. In addition, depending on which receptor is activated, specific members of the SUPPRESSOR OF MAX2 1 (SMAX1)-LIKE (SMXL) family control KAR/KL and SL responses. As proteins that function in the same signal transduction pathway often occur in large protein complexes, we aimed at discovering new players of the MAX2, D14, and KAI2 protein network by tandem affinity purification in Arabidopsis cell cultures. When using MAX2 as a bait, various proteins were copurified, among which were general components of the Skp1-Cullin-F-box complex and members of the CONSTITUTIVE PHOTOMORPHOGENIC 9 signalosome. Here, we report the identification of a novel interactor of MAX2, a type 5 serine/threonine protein phosphatase, designated PHYTOCHROME-ASSOCIATED PROTEIN PHOSPHATASE 5 (PAPP5). Quantitative affinity purification pointed at PAPP5 as being more present in KAI2 rather than in D14 protein complexes. In agreement, mutant analysis suggests that PAPP5 modulates KAR/KL-dependent seed germination under suboptimal conditions and seedling development. In addition, a phosphopeptide enrichment experiment revealed that PAPP5 might dephosphorylate MAX2 in vivo independently of the synthetic SL analog, rac-GR24. Together, by analyzing the protein complexes to which MAX2, D14, and KAI2 belong, we revealed a new MAX2 interactor, PAPP5, that might act through dephosphorylation of MAX2 to control mainly KAR/KL-related phenotypes and, hence, provide another link with the light pathway.

Struk|Sylwia|S|
De Cuyper|Carolien|C|
Jacobs|Anse|A|
Braem|Lukas|L|
Walton|Alan|A|
De Keyser|Annick|A|
Depuydt|Stephen|S|
Vu|Lam Dai|LD|
De Smet|Ive|I|
Boyer|François-Didier|FD|
Eeckhout|Dominique|D|
Persiau|Geert|G|
Gevaert|Kris|K|
De Jaeger|Geert|G|
Goormachtig|Sofie|S|

MAX2
strigolactones
karrikins
affinity purification
seed germination
phosphorylation


A cluster analytic approach to examining the role of cortisol in the development of post-traumatic stress and dysphoria in adult traumatic injury survivors.

Abstract: Identification of specific risk factors for posttraumatic stress disorder (PTSD) versus depression after trauma has been challenging, in part due to the high comorbidity of these disorders. As exposure to trauma triggers activation of the hypothalamic-pituitary-adrenal (HPA)-axis, examining atypical stress responses via HPA-axis hormones, namely cortisol, may help in the delineation of these disorders. Indeed, extant research demonstrates that, following stress, individuals with chronic PTSD exhibit hypocortisolism (e.g., lower cortisol response than controls), while those with chronic depression exhibit hypercortisolism (e.g., higher response than controls). Less is known about the role of cortisol and these seemingly disparate profiles immediately following traumatic injury as well as whether cortisol can be used as a predictor of future development of PTSD versus depression symptoms. In this study cortisol was measured blood from 172 traumatic injury survivors during hospitalization (on average 2.5 days post-injury). PTSD and depression severity were assessed from Clinician Assessed PTSD Scale (CAPS-5) six-eight months later using a two-factor dimensional approach that measures trauma-specific symptoms of PTSD versus dysphoria (akin to depression). Cluster analysis was used to group individuals based on post-injury cortisol, PTSD, and dysphoria. Results demonstrated that trauma survivors who only developed symptoms of dysphoria at six months (with minimal symptoms of PTSD) were differentiated by high post-injury cortisol compared to other groups. By contrast, individuals who developed symptoms of both PTSD and dysphoria were differentiated by low post-injury cortisol and most severe symptoms of PTSD. Findings provide support for the presence of subgroups of trauma survivors defined, in part, by post-trauma cortisol.

Jayan|Devi|D|
deRoon-Cassini|Terri A|TA|
Sauber|Garrett|G|
Hillard|Cecilia J|CJ|
Fitzgerald|Jacklynn M|JM|

Cortisol
Dysphoria
Traumatic injury
PTSD
Depression
Trauma
Cluster analyses


Dexamethasone increases production of C-type natriuretic peptide in the sheep brain.

Abstract: Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose-responsive increases lasting 12-16 h after dexamethasone, whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression (NPPC) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone, despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion.

Wilson|Michele O|MO|
McNeill|Bryony A|BA|
Barrell|Graham K|GK|
Prickett|Timothy C R|TCR|
Espiner|Eric A|EA|

CNP
cerebrospinal fluid
pituitary
NTproCNP
glucocorticoid
natriuretic peptide gene expression


A mechanochemical approach to access the proline-proline diketopiperazine framework.

Abstract: Ball milling was exploited to prepare a substituted proline building block by mechanochemical nucleophilic substitution. Subsequently, the mechanocoupling of hindered proline amino acid derivatives was developed to provide proline-proline dipeptides under solvent-free conditions. A deprotection-cyclization sequence yielded the corresponding diketopiperazines that were obtained with a high stereoselectivity which could be explained by DFT calculations. Using this method, an enantiopure disubstituted Pro-Pro diketopiperazine was synthesized in 4 steps, making 5 new bonds using a ball mill.

Pétry|Nicolas|N| Benakki|Hafid|H| Clot|Eric|E| Retailleau|Pascal|P| Guenoun|Farhate|F| Asserar|Fatima|F| Sekkat|Chakib|C| Métro|Thomas-Xavier|TX| Martinez|Jean|J| Lamaty|Frédéric|F|

diketopiperazine
ball mill
DFT calculations
mechanochemistry
pyrrolidine


Acceptability of mandatory tuberculosis notification among private practitioners in Yogyakarta, Indonesia.

Abstract:
OBJECTIVE
Indonesia ranks second globally in the number of cases not reported to the National Tuberculosis Control Program, accounting for 11% of the total cases lost worldwide. In 2016, the Ministry of Health has issued Regulation Number 67 on tuberculosis control, which requires mandatory tuberculosis notification. We aimed to assess the prospective acceptability of mandatory tuberculosis notification among solo private practitioners and private primary care clinics in Yogyakarta.

RESULTS
Our study highlighted critical issues which need to be addressed in ensuring acceptability of mandatory tuberculosis case notification. We found that that private practitioners do not notify tuberculosis cases due to a lack of policy knowledge. Mandatory tuberculosis notification and its potential penalties were also felt as burdensome by private practitioners. There were ethical concerns among the private practitioners in our study about patient's privacy and patients potentially lost to other healthcare facility. Private practitioners emphasized the need for intervention coherence and cooperation. We also observed pattern variations of these constructs across characteristics of private practitioners.

Acceptability
Tuberculosis
Private practitioners
Indonesia
Mandatory notification


A phase 1b study evaluating the safety and pharmacokinetics of regorafenib in combination with cetuximab in patients with advanced solid tumors.

Abstract: Regorafenib 160 mg orally once daily (QD) 3 weeks on/1 week off is approved in colorectal cancer, gastrointestinal stromal tumors and hepatocellular carcinoma. We established the safety and pharmacokinetics (PK) of regorafenib combined with cetuximab in advanced refractory solid tumors. This was a phase 1, open-label, dose-escalation study (NCT01973868) in patients with advanced/metastatic solid tumors who progressed after standard therapy. Regorafenib was administered at various dose levels QD continuously or intermittently (3 weeks on/1 week off) combined with intravenous cetuximab 250 mg/m2 weekly. The primary objectives were safety, PK and maximum tolerated dose (MTD). The secondary objective was tumor response. Dose-limiting toxicities (DLTs) were evaluated in Cycle 1. Of 42 treated patients, 31 received regorafenib intermittently (120 mg, n = 8; 160 mg, n = 23) and 11 continuously (60 mg, n = 5; 100 mg, n = 6) plus cetuximab. The continuous arm was terminated due to low tolerable dose. In the intermittent arm, one DLT (grade 3 hand-foot skin reaction) was observed at 120 mg but none at 160 mg, therefore 160 mg/day was declared as the MTD in combination with cetuximab. The most common all-grade treatment-emergent adverse events were fatigue (52%), hypophosphatemia (48%) and diarrhea (40%). One grade 3 cetuximab-related dermatitis acneiform was observed. No clinically relevant drug-drug interactions were observed. Five patients (21%) had a partial response. Regorafenib 160 mg QD (3 weeks on/1 week off) plus standard dose of cetuximab was well tolerated with no unexpected toxicities and promising signs of efficacy.

D000971:Antineoplastic Combined Chemotherapy Protocols

regorafenib
cetuximab
phase 1
metastatic colorectal cancer


Coronary artery disease and 10-year outcome after hospital admission for heart failure with preserved and with reduced ejection fraction.

Abstract:
AIMS
The prognostic impact of coronary artery disease (CAD) in heart failure is debated. Whereas causes of death have been well described in patients with cardiomyopathy, little is known about how CAD influences causes of death in heart failure with preserved ejection fraction (HFPEF). We undertook a 10-year study and analysed causes of death in relation with CAD in HFPEF and in heart failure with reduced ejection fraction (HFREF).

METHODS AND RESULTS
Our prospective analysis included 591 consecutive patients (320 HFPEF and 271 HFREF) hospitalized for the first time for heart failure during 2000 and followed for 10 years. History of CAD was documented in 25% of HFPEF and 39% of HFREF patients (P < 0.001). Overall, CAD was independently predictive of all-cause and cardiovascular death. CAD had powerful prognostic impact in HFREF [adjusted hazard ratio (HR) 1.60 (1.19-2.15) for all-cause death, and adjusted HR 2.01 (1.38-2.92) for cardiovascular death]. In HFPEF, the association between CAD and cardiovascular death was no longer observed after adjustment [adjusted HR 1.01 (0.69-1.50)]. In HFREF, CAD was associated with increased risk of heart failure-related (adjusted HR 2.03 (1.21-3.43)] and myocardial infarction-related fatal events [adjusted HR 3.84 (1.16-12.7)], while HFPEF patients with CAD appeared at greater risk of sudden death [adjusted HR 2.22 (1.05-4.95)].

CONCLUSION
The prognostic impact of CAD is different in HFPEF compared with HFREF. Patients with HFPEF and CAD are at high risk of cardiovascular death, especially sudden death.

Rusinaru|Dan|D| Houpe|David|D| Szymanski|Catherine|C| Lévy|Franck|F| Maréchaux|Sylvestre|S| Tribouilloy|Christophe|C|

Coronary Artery Disease
Heart Failure
Causes of Death
Prognosis


Exosomes and Obesity-Related Insulin Resistance.

Abstract: Exosomes are extracellular vesicles, delivering signal molecules from donor cells to recipient cells. The cargo of exosomes, including proteins, DNA and RNA, can target the recipient tissues and organs, which have an important role in disease development. Insulin resistance is a kind of pathological state, which is important in the pathogeneses of type 2 diabetes mellitus (T2DM), gestational diabetes mellitus and Alzheimer's disease. Furthermore, obesity is a kind of inducement of insulin resistance. In this review, we summarized recent research advances on exosomes and insulin resistance, especially focusing on obesity-related insulin resistance. These studies suggest that exosomes have great importance in the development of insulin resistance in obesity and have great potential for use in the diagnosis and therapy of insulin resistance.

Lei|Li-Min|LM| Lin|Xiao|X| Xu|Feng|F| Shan|Su-Kang|SK| Guo|Bei|B| Li|Fu-Xing-Zi|FX| Zheng|Ming-Hui|MH| Wang|Yi|Y| Xu|Qiu-Shuang|QS| Yuan|Ling-Qing|LQ|

exosomes
insulin resistance
obesity
inflammation
mesenchymal stem cell


Heat transfer analysis of skin during thermal therapy using thermal wave equation.

Abstract: Specifying exact geometry of vessel network and its effect on temperature distribution in living tissues is one of the most complicated problems of the bioheat field. In this paper, the effects of blood vessels on temperature distribution in a skin tissue subjected to various thermal therapy conditions are investigated. Present model consists of counter-current multilevel vessel network embedded in a three-dimensional triple-layered skin structure. Branching angles of vessels are calculated using the physiological principle of minimum work. Length and diameter ratios are specified using length doubling rule and Cube law, respectively. By solving continuity, momentum and energy equations for blood flow and Pennes and modified Pennes bioheat equations for the tissue, temperature distributions in the tissue are measured. Effects of considering modified Pennes bioheat equation are investigated, comprehensively. It is also observed that blood has an impressive role in temperature distribution of the tissue, especially at high temperatures. The effects of different parameters such as boundary conditions, relaxation time, thermal properties of skin, metabolism and pulse heat flux on temperature distribution are investigated. Tremendous effect of boundary condition type at the lower boundary is noted. It seems that neither insulation nor constant temperature at this boundary can completely describe the real physical phenomena. It is expected that real temperature at the lower levels is somewhat between two predicted values. The effect of temperature on the thermal properties of skin tissue is considered. It is shown that considering temperature dependent values for thermal conductivity is important in the temperature distribution estimation of skin tissue; however, the effect of temperature dependent values for specific heat capacity is negligible. It is seen that considering modified Pennes equation in processes with high heat flux during low times is significant.

Kashcooli|Meisam|M|
Salimpour|Mohammad Reza|MR|
Shirani|Ebrahim|E|

D001808:Blood Vessels
D006801:Humans
D006979:Hyperthermia, Induced
D008962:Models, Theoretical
D012867:Skin
D012881:Skin Temperature
D013814:Thermal Conductivity

Thermal therapy
Triple-layered skin
Relaxation time
Modified Pennes equation
Counter-current vessels


Field practice study of half-dose sorafenib treatment on safety and efficacy for hepatocellular carcinoma: A propensity score analysis.

Abstract:
AIM
Patients with hepatocellular carcinoma (HCC) who receive an initial full dose of sorafenib (800 mg/day) often require a decreased dose (400 mg/day) or discontinuation of therapy because of severe adverse events. We conducted a retrospective analysis of patients with HCC to compare the safety and efficacy of full- to half-dose sorafenib.

METHODS
We reviewed the medical records of 218 consecutive patients with intermediate or advanced stage HCC who received half (n = 73) or full-dose sorafenib (n = 145) between 2009 and 2012 at four institutions. A propensity score-matching analysis was used to adjust for potential bias.

RESULTS
Multivariate logistic regression analysis showed that increased age was an independent factor for the selection of initial half-dose sorafenib (odds ratio, 1.10; 95% confidence interval, 1.05-1.15; P < 0.001). Fifty-eight patients each in the half-dose and full-dose groups were selected for propensity score matching. The incidence of grade 3-4 severe adverse effects was lower in the half-dose group (47.4% vs 66.7%, P = 0.037). In contrast, the median progression-free survival (PFS) and overall survival (OS) rates were not significantly different (half-dose group, 3.8 and 10.2 months; full-dose group, 2.5 and 8.8 months; P = 0.143 and 0.911, respectively).

CONCLUSION
Propensity score-matched analyses indicate that initial half-dose sorafenib treatment led to fewer severe adverse effects and a comparable survival benefit compared with a full dose in select patients with HCC, particularly for those of advanced age.

Morimoto|Manabu|M| Numata|Kazushi|K| Kondo|Masaaki|M| Kobayashi|Satoshi|S| Ohkawa|Shinichi|S| Hidaka|Hisashi|H| Nakazawa|Takahide|T| Okuwaki|Yusuke|Y| Okuse|Chiaki|C| Matsunaga|Kotaro|K| Suzuki|Michihiro|M| Morita|Satoshi|S| Taguri|Masataka|M| Tanaka|Katsuaki|K|

sorafenib
hepatocellular carcinoma
propensity score
dose
age
adverse drug reaction


Engine parameter optimization of palm oil biodiesel as alternate fuel in CI engine.

Abstract: Stringent emission regulations and depletion of crude oil are driving researchers toward alternative fuels. In this context, palm oil emerges as a good competitor as it is highly economical compared to other alternative fuels. The current research work centers around the impact of palm oil methyl ester on performance, combustion, and emission characteristics at varying injection timings and exhaust gas recirculation rates. In the first phase of this research work, various blends of palm oil methyl ester with diesel with volume concentrations of 10, 20, and 30% were prepared and tested at different load conditions. Injection timing was then varied for the optimized blend. In the second phase, the impact of exhaust gas blending with fresh charge was studied at optimized injection timing. The test outcomes revealed that 20% mix of palm oil at 27° bTDC with exhaust gas blending of 20% generated higher brake thermal efficiency, higher peak pressure, and less hydrocarbon and nitrogen oxide emissions compared to diesel at standard injection timing of 23° bTDC and no blending of exhaust gases with fresh charge. However, progression of injection timing with 20% exhaust gas mixing indicated a slight penalty in smoke discharges. Brake thermal efficiency at advanced injection timing with 20% mix of exhaust gases reduced by 7.7% for diesel and increased by 6.5% for 20% blend of palm oil when compared to standard injection timing of diesel and no blending of exhaust gases. Significant diminishments in oxides of nitrogen (lessened by 6.6%) and hydrocarbons (decreased by 30.43%) have been noted for 20% mix of biodiesel at advanced injection timing with 20% exhaust gas mix contrasted to diesel at standard conditions. Therefore, the present examination prescribes 20% merging of exhaust gases for 20% blend of palm oil with advancement of injection timing for diesel engine applications.

Kumar|Akula Naresh|AN|
Kishore|Pisipaty Srinivas|PS|
Raju|Kalidindi Brahma|KB|
Kasianantham|Nanthagopal|N|
Bragadeshwaran|Ashok|A|

Palm oil
Biodiesel
Methyl ester
Injection timing
Exhaust gas recirculation


Clinical effects and safety of different strategies for administering intravenous diuretics in acutely decompensated heart failure: a randomised clinical trial.

Abstract:
BACKGROUND
The mainstay of treatment for acutely decompensated heart failure (ADHF) is intravenous diuretic therapy either as a bolus or via continuous infusion.

OBJECTIVES
We evaluated the clinical effects and safety of three strategies of intravenous furosemide administration used in emergency departments (EDs) for ADHF.

METHODS
We performed a multicentre, randomised, parallel-group study. Patients with ADHF were randomised within 2 h of ED arrival to receive furosemide by continuous infusion (10 mg/h, group 1) or boluses (20 mg/6 h, group 2; or 20 mg/8 h, group 3). The primary end point was total diuresis, and secondary end points were dyspnoea, orthopnoea, extension of rales and peripheral oedema, blood pressure, respiratory and heart rates, and pulse oximetry, which were measured at arrival and 3, 6, 12 and 24 h after treatment onset. We also measured serum creatinine, sodium and potassium levels at arrival and after 24 h.

RESULTS
Group 1 patients (n=36) showed greater 24 h diuresis (3705 mL) than those in groups 2 (n=37) and 3 (n=36) (3093 and 2670 mL, respectively; p<0.01), and this greater diuretic effect was observed earlier. However, no differences were observed among groups in the nine secondary clinical end points evaluated. Creatinine deterioration developed in 15.6% of patients, hyponatraemia in 9.2%, and hypokalaemia in 19.3%, with the only difference among groups observed in hypokalaemia (group 1, 36.3%; group 2, 13.5%; group 3, 8.3%; p<0.01).

CONCLUSIONS
In patients with ADHF attending the ED, boluses of furosemide have a smaller diuretic effect but provide similar clinical relief, similar preservation of renal function, and a lower incidence of hypokalaemia than continuous infusion.

TRIAL REGISTRATION NUMBER
This randomised trial was registered in the European Clinical Trial Database (EudraCT) with the reference number 2008-004488-20.

Llorens|Pere|P|
Miró|Òscar|Ò|
Herrero|Pablo|P|
Martín-Sánchez|Francisco Javier|FJ|
Jacob|Javier|J|
Valero|Amparo|A|
Alonso|Héctor|H|
Pérez-Durá|María José|MJ|
Noval|Antonio|A|
Gil-Román|José Juan|JJ|
Zapater|Pedro|P|
Llanos|Lucía|L|
Gil|Víctor|V|
Perelló|Rafel|R|

heart failure
treatment
emergency departments