Lid wiper epitheliopathy.

Abstract: Some recent research has resulted in a hypothesis that there is a common 'lid wiper' region that is apposite to the ocular surface or anterior lens surface (where contact lenses are worn), responsible for spreading tears during blinking. In the upper eyelid, it extends about 0.6 mm from the crest of the sharp posterior (inner) lid border (i.e. the mucocutaneous junction, or line of Marx) to the subtarsal fold superiorly and from the medial upper punctum to the lateral canthus horizontally. Histologically, it is seen as an epithelial elevation comprising of stratified epithelium with a transitional conjunctival structure of (moving posteriorly) squamous cells then cuboidal cells, with some parakeratinised cells and goblet cells. Lid wiper epitheliopathy (LWE) denotes staining of the lid wiper observed after instillation of dyes such as fluorescein, rose bengal or lissamine green. There have been some reports of higher rates of LWE in dry eye patients and contact lens wearers, but others have failed to find such associations. The primary cause of LWE is thought to be increased friction between the lid wiper and ocular or anterior contact lens surface due to inadequate lubrication, which could be caused by dry eye and may be exacerbated by factors such as abnormal blinking patterns, poor contact lens surface lubricity and adverse environmental influences. Recent evidence suggests that LWE is associated with sub-clinical inflammation. LWE has the potential to provide the missing mechanistic link between clinical observation and symptoms associated with dry eye and contact lens wear. Clinical and fundamental research into LWE is still in its infancy and in many instances equivocal; however, it is an idea that provides a potentially important new avenue for further investigation of anterior eye discomfort associated with ocular dryness and contact lens wear.

Efron|Nathan|N|
Brennan|Noel A|NA|
Morgan|Philip B|PB|
Wilson|Tawnya|T|

Lid wiper epitheliopathy
Dry eye
Contact lens
Eye lids


Prediction Models for Early Childhood Obesity: Applicability and Existing Issues.

Abstract: Statistical models have been developed for the prediction or diagnosis of a wide range of outcomes. However, to our knowledge, only 7 published studies have reported models to specifically predict overweight and/or obesity in early childhood. These models were developed using known risk factors and vary greatly in terms of their discrimination and predictive capacities. There are currently no established guidelines on what constitutes an acceptable level of risk (i.e., risk threshold) for childhood obesity prediction models, but these should be set following consideration of the consequences of false-positive and false-negative predictions, as well as any relevant clinical guidelines. To date, no studies have examined the impact of using early childhood obesity prediction models as intervention tools. While these are potentially valuable to inform targeted interventions, the heterogeneity of the existing models and the lack of consensus on adequate thresholds limit their usefulness in practice.

Butler|Éadaoin M|ÉM|
Derraik|José G B|JGB|
Taylor|Rachael W|RW|
Cutfield|Wayne S|WS|

Overweight Risk Intervention Children Prevention


Anti-glioma properties of DVL, a lectin purified from Dioclea violacea.

Abstract: Plant lectins have been studied owing to their structural properties and biological effects that include agglutinating activity, antidepressant-like effect and antitumor property. The results from this work showed the effects of the lectin extracted from the Dioclea violacea plant (DVL) on the C6 rat glioma cell line. DVL treatment was able to induce caspase-3 activation, apoptotic cell death and cellular membrane damage. Furthermore, DVL decreased mitochondrial membrane potential and increased the number of acidic vesicles and cleavage of LC3, indicating activation of autophagic processes. DVL also significantly inhibited cell migration. Compared to ConA, a well-studied lectin extracted from Canavalia ensiformes seeds, some effects of DVL were more potent, including decreasing C6 glioma cell viability and migration ability. Taken together, the results suggest that DVL can induce glioma cell death, autophagy and inhibition of cell migration, displaying potential anti-glioma activity.

Nascimento|Ana Paula M|APM|
Knaut|Jhônatas L|JL|
Rieger|Débora K|DK|
Wolin|Ingrid A V|IAV|
Heinrich|Isabella A|IA|
Mann|Josiane|J|
Juarez|Andrea V|AV|
Sosa|Liliana Del V|LDV|
De Paul|Ana Lucia|AL|
Moreira|Cleane G|CG|
Silva|Ivanice B|IB|
Nobre|Clareane S|CS|
Osterne|Vinicius J S|VJS|
Nascimento|Kyria S|KS|
Cavada|Benildo S|BS|
Leal|Rodrigo B|RB|

DVL
Lectin
Dioclea violacea
Glioma
ConA
Autophagy


Of Molecules and Mechanisms.

Abstract: Without question, molecular biology drives modern neuroscience. The past 50 years has been nothing short of revolutionary as key findings have moved the field from correlation toward causation. Most obvious are the discoveries and strategies that have been used to build tools for visualizing circuits, measuring activity, and regulating behavior. Less flashy, but arguably as important are the myriad investigations uncovering the actions of single molecules, macromolecular structures, and integrated machines that serve as the basis for constructing cellular and signaling pathways identified in wide-scale gene or RNA studies and for feeding data into informational networks used in systems biology. This review follows the pathways that were opened in neuroscience by major discoveries and set the stage for the next 50 years.

D000818:Animals
D064113:CRISPR-Cas Systems
D005089:Exocytosis
D005786:Gene Expression Regulation
D018014:Gene Transfer Techniques
D017930:Genes, Reporter
D049673:History, 20th Century
D049674:History, 21st Century
D006801:Humans
D017403:In Situ Hybridization
D008853:Microscopy
D008967:Molecular Biology
D009419:Nerve Tissue Proteins
D009488:Neurosciences
D054731:PDZ Domains
D016133:Polymerase Chain Reaction
D015202:Protein Engineering
D012313:RNA
D011994:Recombinant Proteins
D017422:Sequence Analysis, DNA

RNA
CRISPR-Cas9
PCR
SNARE and synapse composition
nanoscale imaging
transfection and transduction


The association of repeated measurements of prenatal exposure to triclosan with fetal and early-childhood growth.

Abstract:
BACKGROUND
Triclosan (TCS) is known to possess endocrine disrupting properties and metabolize rapidly in the human body. Human data concerning repeated measurements of TCS throughout pregnancy in relation to fetal and childhood growth are sparse.

OBJECTIVES
We investigated the associations between multiple measurements of maternal urinary concentrations of TCS during pregnancy and fetal and early-childhood growth.

METHODS
The study population included 850 mother-infant pairs who participated in a prenatal cohort established between 2014 and 2015 in Wuhan. Prenatal TCS exposure was measured in a complete series of urine samples collected at the first, second and third trimesters. General linear models and generalized estimating equation models were applied to evaluate the associations of the averaged maternal urinary concentrations of TCS over trimesters and trimester-specific urinary TCS with the z-scores of estimated fetal weight, head circumference, abdominal circumference, and femur length at 16, 24, and 31 gestational weeks, weight and length at birth, and weight and height at 0.5, 1, and 2 years of age.

RESULTS
In overall infants, we did not observe any significant association of the averaged maternal urinary concentrations of TCS over trimesters with ultrasound parameters and size at birth. However, a positive association of borderline statistical significance was found between averaged prenatal TCS exposure and the third-trimester estimated fetal weight z-score in girls in sex-stratified analyses (β = 0.054, 95% CI: -0.005, 0.113, p = 0.07). Moreover, averaged prenatal TCS exposure was positively associated with 2 year-old weight z-score among total infants (β = 0.046, 95% CI: 0.005, 0.087). After stratifying by sex, the same association was observed in girls with more prominent estimation (β = 0.062, 95% CI: 0.000, 0.124), whereas the association weakened and became not significant in boys (β = 0.033, 95% CI: -0.024, 0.089). TCS exposure at 1st and 2nd-trimester were positively associated with weight z-score at 2 years, in both overall and female infants.

CONCLUSIONS
Prenatal exposure to triclosan was associated with elevated third-trimester estimated fetal weight and 2 year-old weight z-score in girls, and the early and middle stage of pregnancy may be the windows of vulnerability. Apart from these findings, we did not find strong evidence for prenatal triclosan exposure in relation to fetal and early-childhood growth.

Wu|Chuansha|C| Li|Jiufeng|J| Xia|Wei|W| Li|Yuanyuan|Y| Zhang|Bin|B| Zhou|Aifen|A| Hu|Jie|J| Li|Chunhui|C| Zhao|Hongzhi|H| Jiang|Minmin|M| Hu|Chen|C| Liao|Jiaqiang|J| Huo|Wenqian|W| Chen|Xi|X| Xu|Bing|B| Lu|Shi|S| Cai|Zongwei|Z| Xu|Shunqing|S|

Repeated measurements
Triclosan
Early-childhood growth
Fetal growth


Lung Cancer Screening with Low-Dose CT: a Meta-Analysis.

Abstract:
BACKGROUND
Randomized controlled trials have evaluated the efficacy of low-dose CT (LDCT) lung cancer screening on lung cancer (LC) outcomes.

OBJECTIVE
Meta-analyze LDCT lung cancer screening trials.

METHODS
We identified studies by searching PubMed, Google Scholar, the Cochrane Registry, ClinicalTrials.gov , and reference lists from retrieved publications. We abstracted data on study design features, stage I LC diagnoses, LC and overall mortality, false positive results, harm from invasive diagnostic procedures, overdiagnosis, and significant incidental findings. We assessed study quality using the Cochrane risk-of-bias tool. We used random-effects models to calculate relative risks and assessed effect modulators with subgroup analyses and meta-regression.

RESULTS
We identified 9 studies that enrolled 96,559 subjects. The risk of bias across studies was judged to be low. Overall, LDCT screening significantly increased the detection of stage I LC, RR = 2.93 (95% CI, 2.16-3.98), I2 = 19%, and reduced LC mortality, RR = 0.84 (95% CI, 0.75-0.93), I2 = 0%. The number needed to screen to prevent an LC death was 265. Women had a lower risk of LC death (RR = 0.69, 95% CI, 0.40-1.21) than men (RR = 0.86, 95% CI, 0.66-1.13), p value for interaction = 0.11. LDCT screening did not reduce overall mortality, RR = 0.96 (95% CI, 0.91-1.01), I2 = 0%. The pooled false positive rate was 8% (95% CI, 4-18); subjects with false positive results had < 1 in 1000 risk of major complications following invasive diagnostic procedures. The most valid estimates for overdiagnosis and significant incidental findings were 8.9% and 7.5%, respectively.

DISCUSSION
LDCT screening significantly reduced LC mortality, though not overall mortality, with women appearing to benefit more than men. The estimated risks for false positive results, screening complications, overdiagnosis, and incidental findings were low. Long-term survival data were available only for North American and European studies limiting generalizability.

lung cancer screening
meta-analysis
mortality
low-dose computed tomography
lung neoplasms


Pteropine Orthoreovirus in an Angolan Soft-Furred Fruit Bat (Lissonycteris angolensis) in Uganda Dramatically Expands the Global Distribution of an Emerging Bat-Borne Respiratory Virus.

Abstract: Pteropine orthoreovirus (PRV; Reoviridae: Spinareovirinae) is an emerging bat-borne zoonotic virus that causes influenza-like illness (ILI). PRV has thus far been found only in Australia and Asia, where diverse old-world fruit bats (Pteropodidae) serve as hosts. In this study, we report the discovery of PRV in Africa, in an Angolan soft-furred fruit bat (Lissonycteris angolensis ruwenzorii) from Bundibugyo District, Uganda. Metagenomic characterization of a rectal swab yielded 10 dsRNA genome segments, revealing this virus to cluster within the known diversity of PRV variants detected in bats and humans in Southeast Asia. Phylogeographic analyses revealed a correlation between geographic distance and genetic divergence of PRVs globally, which suggests a geographic continuum of PRV diversity spanning Southeast Asia to sub-Saharan Africa. The discovery of PRV in an African bat dramatically expands the geographic range of this zoonotic virus and warrants further surveillance for PRVs outside of Southeast Asia.

Bennett|Andrew J|AJ|
Goldberg|Tony L|TL|0000-0003-3962-4913

pteropine orthoreovirus
bats
reoviridae
emerging respiratory infections


Respiratory stress in mitochondrial electron transport chain complex mutants of Candida albicans activates Snf1 kinase response.

Abstract: We have previously established that mitochondrial Complex I (CI) mutants of Candida albicans display reduced oxygen consumption, decreased ATP production, and increased reactive oxidant species (ROS) during cell growth. Using the Seahorse XF96 analyzer, the energetic phenotypes of Electron Transport Chain (ETC) complex mutants are further characterized in the current study. The underlying regulation of energetic changes in these mutants is determined in glucose and non-glucose conditions when compared to wild type (WT) cells. In parental cells, the rate of oxygen consumption remains constant for 2.5 h following the addition of glucose, oligomycin, and 2-DG, but glycolysis is highly active upon the addition of glucose. In comparison, over the same time period, electron transport complex mutants (CI, CIII and CIV) have heightened activities in both oxygen consumption and glycolysis upon glucose uptake. We refer to the response in these mutants as an "explosive respiration," which we believe is caused by low energy levels and increased production of reactive oxygen species (ROS). Accompanying this phenotype in mutants is a hyperphosphorylation of Snf1p which in Saccharomyces cerevisiae serves as an energetic stress response protein kinase for maintaining energy homeostasis. Compared to wild type cells, a 2.9- to 4.4-fold hyperphosphorylation of Snf1p is observed in all ETC mutants in the presence of glucose. However, the explosive respiration and hyperphosphorylation of Snf1 can be partially reduced by the replacement of glucose with either glycerol or oleic acid in a mutant-specific manner. Furthermore, Inhibitors of glutathione synthesis (BSO) or anti-oxidants (mito-TEMPO) likewise confirmed an increase of Sfn1 phosphorylation in WT or mutant due to increased levels of ROS. Our data establish the role of the C. albicans Snf1 as a surveyor of cell energy and ROS levels. We interpret the "explosive respiration" as a failed attempt by ETC mutants to restore energy and ROS homeostasis via Snf1 activation. An inherently high OCR baseline in WT C. albicans with a background level of Snf1 activation is a prerequisite for success in quickly fermenting glucose.

Zhang|Pengyi|P|
Li|Hongbin|H|
Cheng|Jie|J|
Sun|April Y|AY|
Wang|Liqing|L|
Mirchevska|Gordana|G|
Calderone|Richard|R|
Li|Dongmei|D|

Candida albicans
ROS
Energy phenotype
Mitochondrial respiration
Snf1 kinase phosphorylation


Recall of consent information by day care prostate biopsy patients: An assessment of the role of a third-party check.

Abstract:
Background
To evaluate the extent of recall of consent information by daycare prostate biopsy patients in our low-literacy setting. And to evaluate the role of a 3rd party check on patient's recall of consent information.

Subjects and Methods
As part of our standard of care, a formal informed consent session for day care prostate biopsy takes place 3 days prior to the procedure. For this study, before leaving the outpatient clinic the same day, the patient acknowledged before a third-party that his concerns were or were not satisfactorily addressed. The extent of recall of consent information was assessed on the morning of the procedure using a researcher-administered questionnaire. Consecutive patients participated in this cross-sectional study for day care prostate biopsy at a tertiary hospital in southeast Nigeria from February to November 2015 after obtaining due consent.

Results
The recall of the risks associated with the planned procedure was poorer than the recall of the nature of the disease condition or the nature of the planned procedure. However, it was observed that aggregate recall was significantly poorer among patients who negatively attested to a satisfying consent session (OR 0.125; P < 0.0005).

Conclusion
The use of a third-party in determining patient satisfaction after a consent session may be a better indicator of patient comprehension and subsequent recall of consent information, especially in low-literacy settings. Using a third-party, in this manner, may assist in checking paternalism inherent in the patient-doctor relationship.

Nnabugwu|I I|II|
Ugwumba|F O|FO|
Udeh|E I|EI|
Anyimba|S K|SK|

prostate biopsy
third-party check
patient satisfaction
Consent-information recall


Genomic characterization of chromosome translocations in patients with T/myeloid mixed-phenotype acute leukemia.

Abstract: Mixed-phenotype acute leukemia (MPAL) is a progenitor type of leukemia with ambiguous expression of lineage markers. The diagnosis of MPAL is based on flow cytometric analysis of immunophenotype, which commonly identifies myeloid lineage markers as well as B- or T- lymphoid lineage markers on leukemic blasts. Due to the rare occurrence of this disease, few studies have delineated the molecular bases of MPAL. Combining conventional karyotyping with whole genomic sequencing (WGS) and RNA sequencing (RNA-seq), we report here our identification and characterization of chromosome translocations, gene mutations and gene expression profile in four patients with T/Myeloid MPAL, including two t(6;14)(q25;q32) one t(8;14)(q24.2;q32) and one t(7;8)(p14;q24.2). Notably, seven of the eight translocation breakpoints reside in the non-coding regions and their locations appear to be shared by two or more patients. Gene expression analysis of matched diagnostic vs. remission samples provided evidence of transcriptomes alteration involving nucleosome organization and chromatin assembly.

Pallavajjala|Aparna|A|
Kim|Daehwan|D|
Li|Tongbin|T|
Ghiaur|Gabriel|G|
Jones|Richard J|RJ|
Burns|Kathleen H|KH|
Salzberg|Steven L|SL|
Ning|Yi|Y|

D015973:Gene Expression Regulation, Leukemic

D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Leukemic progenitor cells
cytogenetics
molecular genetics


Modifications to the HIV-1 SAAVI MVA-C vaccine improve in vitro expression and in vivo immunogenicity.

Abstract: Two HIV-1 vaccines (SAAVI DNA-C2 and SAAVI MVA-C) were previously developed in South Africa and tested in preclinical studies and Phase 1 clinical trials. Here we report on improvements made to the SAAVI MVA-C vaccine design which include: the use of different promoters for both the Gag and Env genes, replacement of the native Gag gene with an in silico designed subtype C mosaic Gag antigen which forms virus-like particles and the modification of Env by sequence changes to improve stability and transport to the cell surface. A head-to-head comparison of the newly conceived MVAGD5 candidate vaccine with SAAVI MVA-C showed increased in vitro expression of both Env and Gag, and superior immunogenicity in rabbits. MVAGD5 induced high levels of binding antibodies to Env and Tier 1A and 1B neutralizing antibodies, neither of which were induced by SAAVI MVA-C.

Douglass|Nicola|N|
van Diepen|Michiel T|MT|
Chapman|Rosamund|R|
Galant|Shireen|S|
Margolin|Emmanuel|E|
Ximba|Phindile|P|
Hermanus|Tandile|T|
Moore|Penny L|PL|
Williamson|Anna-Lise|AL|

Immunogenicity
HIV-1 vaccines
Env
Neutralization
Gag mosaic
MVA


The fate of incomplete scaffold apposition of everolimus-eluting bioresorble scaffolds: A serial optical coherence tomography analysis.

Abstract:
BACKGROUND
Incomplete stent apposition (ISA) can be divided into acute and late forms. Late ISA may be due to persistent ISA or late-acquired ISA (LAISA). This study evaluated the natural course of ISA after bioresorbable vascular scaffold (BRS) implantation using optical coherence tomography (OCT).

METHODS
Thirty-two patients (45 BRS) were assessed immediately after BRS implantation and 1 year thereafter using OCT. Acute ISA identified after BRS implantation but absent at follow-up was defined as resolved; otherwise, it was considered persistent. LAISA was defined as newly developed ISA that was identified at follow-up despite complete apposition immediately after BRS implantation. Intra-BRS fibrin-like material (IBF) was identified as an irregular intraluminal mass. ISA percentage was expressed as follows: (number of ISA/total number of BRS struts)×100.

RESULTS
Among 45 BRS and 15,894 analyzed BRS struts, 34 and 882 had acute ISA post-procedure, respectively. At follow-up, 92 of 15,364 analyzed struts exhibited late ISA (64 persistent ISA and 28 LAISA). In 15 of 28 struts with LAISA, LAISA occurred at the sites adjacent to post-interventional dissection. Uncovered struts were more frequently observed in late ISA compared to apposed struts (3.7±4.8 vs. 0.58±2.2%, p=0.09). IBF was significantly more common in BRS with late ISA (62.5 vs. 8.1%, p=0.02). Receiver-operating characteristic curve analysis identified a cut-off value of 280μm for acute ISA distance predicting persistent ISA.

CONCLUSION
Resolution of acute ISA after BRS is common. The occurrence of LAISA may be infrequent and may be a nidus of stent thrombosis.

Sato|Takao|T|
Tölg|Ralph|R|
El-Mawardy|Mohamed|M|
Sulimov|Dmitriy S|DS|
Richardt|Gert|G|
Abdel-Wahab|Mohamed|M|

Optical coherence tomography
Thrombosis
Bioresorbable scaffolds
Malapposition


Case Report: A Case of Leukocyte Adhesion Deficiency, Type III Presenting With Impaired Platelet Function, Lymphocytosis and Granulocytosis.

Abstract: Fermitin family homolog 3 (FERMT3), alternatively kindlin-3 (KIND3), is an integrin binding protein (of 667 residues) encoded by the FERMT3 gene. The molecule is essential for activating integrin αIIbβ3 (the fibrinogen receptor) on platelets and for the integrin-mediated hematopoietic cell (including platelets, T lymphocytes, B lymphocytes, and granulocytes) adhesion. Its defects are associated with impaired primary hemostasis, described as "Glanzmann's thrombasthenia (MIM#273800)-like bleeding problem." The defects are also associated with infections, designated as "LAD1 (leukocyte adhesion deficiency, type I; MIM#116920)-like immune deficiency." The entity that joins the impaired primary hemostasis with the leukocyte malfunction has been termed "leukocyte adhesion deficiency, type III" (LAD3, autosomal recessive, MIM#612840), representing a defective activation of the integrins β1, β2, and β3 on leukocytes and platelets. Here, we report a male toddler with novel compound heterozygous variants, NM_178443.2(FERMT3):c.1800G>A, p.Trp600* (a non-sense variant) and NM_178443.2(FERMT3):c.2001del p.*668Glufs*106 (a non-stop variant). His umbilical cord separated at about 3 weeks of age. A skin rash (mainly petechiae and purpura) and recurrent episodes of severe epistaxis required blood transfusions in early infancy. His hemostatic work-up was remarkable for a normal platelet count, but abnormal platelet function screen with markedly prolonged collagen-epinephrine and collagen-ADP closure times. The impaired platelet function was associated with reduced platelet aggregation with all agonists. The expression of platelet receptors was normal. Other remarkable findings were persistent lymphocytosis and granulocytosis, representing defects in diapedesis due to the integrin dysfunction. The natural history of his condition, structure and sequence analysis of the variations, and comparison with other LAD3 cases reported in the literature are presented.

Yahya|Amal M|AM|
AlMulla|Asia A|AA|
AlRufaye|Haydar J|HJ|
Al Dhaheri|Ahmed|A|
Elomami|Abdulghani S|AS|
Al-Hammadi|Suleiman|S|
Kailas|Lalitha|L|
Vijayan|Ranjit|R|
Souid|Abdul-Kader|AK|

FERMT3
kindlin-3
epistaxis
BCG vaccine
Glanzmann thrombasthenia
inborn error of immunity
leukocytosis
platelet dysfunction


Inhibition of dengue virus replication in monocyte-derived dendritic cells by vivo-morpholino oligomers.

Abstract: Skin dendritic cells (DCs) are primary target cells of dengue virus (DENV) infection and they play an important role in its immunopathogenesis. Monocyte-derived dendritic cells (MDDCs) represent dermal and bloodstream DCs that serve as human primary cells for ex vivo studies of DENV infection. Improved understanding of the mechanisms that effectuate the inhibition of DENV replication in MDDCs will accelerate the development of antiviral drugs to treat DENV infection. In this study, we investigated whether or not vivo-morpholino oligomer (vivo-MO), which was designed to target the top of the 3' stem-loop (3' SL) at the 3' UTR of the DENV genome, could inhibit DENV infection and replication in MDDCs. The findings of this study revealed that vivo-MO-1 could inhibit DENV-2 infection in MDDCs, and that it could significantly reduce DENV RNA, protein, and viral production in a dose-dependent manner. Treatment of MDDCs with 4 μM of vivo-MO-1 decreased DENV production by more than 1,000-fold, when compared to that of the vivo-MO-NC control. Thus, vivo-MO-1 targeting of DENV RNA demonstrates potential for further development into an anti-DENV agent.

Phumesin|Patta|P| Junking|Mutita|M| Panya|Aussara|A| Yongpitakwattana|Petlada|P| Noisakran|Sansanee|S| Limjindaporn|Thawornchai|T| Yenchitsomanus|Pa-Thai|PT|

D000998:Antiviral Agents
D002478:Cells, Cultured
D003713:Dendritic Cells
D003716:Dengue Virus
D006801:Humans
D016376:Oligonucleotides, Antisense
D014779:Virus Replication

Octaguanidinium dendrimer-conjugated morpholino oligomers


Complete genome sequence of soil actinobacteria Streptomyces cavourensis TJ430.

Abstract: A new actinobacteria Streptomyces cavourensis TJ430 was isolated from the mountain soil collected from the southwest of China. In previous study, TJ430 showed striking bactericidal activities and strong ability of antibiotic production. Here, we report complete genome of this bacterium, consisting of 7.6 Mb linear chromosome and 0.2 Mb plasmids. It was predicted 6450 genes in chromosome and 225 genes in plasmids, as well as 12 gene islands in chromosome. Abundant genes have predicted functions in antibiotic metabolism and stress resistance. A whole-genome comparison of S. cavourensis TJ430, S. coelicolor A3(2), and S. lividans 66 indicates that TJ430 has a relatively high degree of strain specificity. The 16S rRNA phylogenetic tree shows the high identities (99.79%) of TJ430 with S. cavourensis DSM40300. TJ430 is a new and rare Streptomyces species, and analysis of its genome helps us to better understand primary metabolism mechanism of this isolate, as well as the evolutionary biology.

D001482:Base Composition
D001483:Base Sequence
D002681:China
D024881:Drug Resistance, Bacterial
D005798:Genes, Bacterial
D059646:Genome Size
D016680:Genome, Bacterial
D044404:Genomic Islands
D058977:Molecular Sequence Annotation
D010802:Phylogeny
D010957:Plasmids
D012336:RNA, Ribosomal, 16S
D017422:Sequence Analysis, DNA
D012988:Soil Microbiology
D013302:Streptomyces

genome sequence Streptomyces antibiotic resistance


Delayed surgical intervention in central cord syndrome with cervical stenosis.

Abstract: Study Design Review of the literature. Objective It is generally accepted that surgical treatment is necessary for central cord syndrome (CCS) with an underlying cervical stenosis. However, the surgical timing for decompression is controversial in spondylotic cervical CCS. The purpose of this study is to review the results of early and delayed surgery in patients with spondylotic cervical CCS. Methods MEDLINE was searched for English-language articles on CCS. There were 1,653 articles from 1940 to 2012 regarding CCS, 5 of which dealt with the timing of surgery for spondylotic cervical CCS. Results All five reports regarding the surgical timing of spondylotic cervical CCS were retrospective. Motor improvement, functional independence measures, and walking ability showed similar improvement in early and late surgery groups in the studies with follow-up longer than 1 year. However, greater improvement was seen in the early surgery group in the studies with follow-up shorter than 1 year. The complication rates did not show a difference between the early and late surgery groups. However, there are controversies regarding the length of intensive care unit stay or hospital stay for the two groups. Conclusions There was no difference in motor improvement, functional independence, walking ability, and complication rates between early and late surgery for spondylotic cervical CCS.

Park|Moon Soo|MS|
Moon|Seong-Hwan|SH|
Lee|Hwan-Mo|HM|
Kim|Tae-Hwan|TH|
Oh|Jae Keun|JK|
Suh|Bo-Kyung|BK|
Lee|Seung Jin|SJ|
Riew|K Daniel|KD|

central cord syndrome
surgical timing
cervical spine


PREventive Care Infrastructure based On Ubiquitous Sensing (PRECIOUS): A Study Protocol.

Abstract:
BACKGROUND
mHealth has experienced a huge growth during the last decade. It has been presented as a new and promising pathway to increase self-management of health and chronic conditions in several populations. One of the most prolific areas of mHealth has been healthy lifestyles promotion. However, few mobile apps have succeeded in engaging people and ensuring sustained use.

OBJECTIVE
This paper describes the pilot test protocol of the PReventive Care Infrastructure based on Ubiquitous Sensing (PRECIOUS) project, aimed at validating the PRECIOUS system with end users. This system includes, within a motivational framework, the Bodyguard2 sensor (accelerometer with heart rate monitoring) and the PRECIOUS app.

METHODS
This is a pilot experimental study targeting morbidly obese prediabetic patients who will be randomized to three conditions: (1) Group 1 - Control group (Treatment as usual with the endocrinologist and the nurse + Bodyguard2), (2) Group 2 - PRECIOUS system (Bodyguard2 + PRECIOUS app), and (3) Group 3 - PRECIOUS system (Bodyguard2 + PRECIOUS app + Motivational Interviewing). The duration of the study will be 3 months with scheduled follow-up appointments within the scope of the project at Weeks 3, 5, 8, and 12. During the study, several measures related to healthy lifestyles, weight management, and health-related quality of life will be collected to explore the effectiveness of PRECIOUS to foster behavior change, as well as user acceptance, usability, and satisfaction with the solution.

RESULTS
Because of the encouraging results shown in similar scientific work analyzing health apps acceptance in clinical settings, we expect patients to widely accept and express satisfaction with PRECIOUS. We also expect to find acceptable usability of the preventive health solution. The recruitment of the pilot study has concluded with the inclusion of 31 morbidly obese prediabetic patients. Results are expected to be available in mid-2017.

CONCLUSIONS
Adopting and maintaining healthy habits may be challenging in people with chronic conditions who usually need regular support to ensure mid/long-term adherence to recommendations and behavior change. Thus, mHealth could become a powerful and efficient tool since it allows continuous communication with users and immediate feedback. The PRECIOUS system is an innovative preventive health care solution aimed at enhancing inner motivation from users to change their lifestyles and adopt healthier habits. PRECIOUS includes ubiquitous sensors and a scientifically grounded app to address three main components of health: physical activity, diet, and stress levels.

TRIAL REGISTRATION
Clinicaltrials.gov NCT02818790; https://clinicaltrials.gov/ct2/show/NCT02818790 (Archived by WebCite at http://www.webcitation.org/6qfzdfMoU).

mHealth
motivational interviewing
adherence
physical activity
diet
sustained motivation


Factors influencing women's sex work in a Lebanese sample: results of a case-control study.

Abstract:
BACKGROUND
Many constituents contribute to the rise of sex work in Lebanon such as the socio-economic situation in the country (poverty, increased unemployment rates, and religious divisions), as well as the political and social instability. Several emotional and psychological factors such as depression, stress, anxiety, low self-esteem, emotional abuse, may force some people to rely on trading sex as a coping strategy for persevering. Therefore, it was deemed interesting to explore and understand factors that are correlated with sex work in Lebanon where no study, to our knowledge, has been written on this critical point. The objective of the study was to assess factors (such as trauma, child abuse, partner abuse, depression, anxiety, and stress) associated with women joining sex work among a sample of the Lebanese population.

METHODS
A case-control study was conducted on a group of women (60 sex workers recruited from a prison for women) involved in sex work matched for age and sex with a control group (60 non-sex workers). Controls were chosen from the same prison population as the sex workers.

RESULTS
A logistic regression was conducted, taking being a sex worker vs not as the dependent variable; independent factors were sociodemographic characteristics, child (psychological, neglect, physical and verbal) and inter partner violence (physical and non-physical), depression, anxiety and stress. Higher anxiety (aOR = 1.08) and higher inter partner physical violence (aOR = 1.02) were altogether related with higher chances of being a sex worker.

CONCLUSION
This study proposes an association between child abuse, inter partner violence, alcohol consumption, anxiety, and sex work. Future research may also need to contemplate other factors not examined here, including parental substance use, personality traits, and many others.

Slim|Maria|M| Haddad|Chadia|C| Sfeir|Elsa|E| Rahme|Clara|C| Hallit|Souheil|S|0000-0001-6918-5689 Obeid|Sahar|S|

D000069586:Adult Survivors of Child Adverse Events

Sex work
Anxiety
Child abuse
Partner abuse
Sex workers
Alcohol drinking


Beyond acute cholecystitis-gallstone-related complications and what the emergency radiologist should know.

Abstract: The purpose of this study is to emphasize the imaging features of complications of gallstones beyond the cystic duct on ultrasound (US), enhanced and nonenhanced computed tomography (CECT and NECT), magnetic resonance imaging (MRI), magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP). This article includes a brief overview of gallstone imaging and emerging trends in the detection of gallstones. This review article will highlight complications of gallstones, including choledocholithiasis, gallstone pancreatitis, acute cholangitis, Mirizzi syndrome, cholecystobiliary and cholecystoenteric fistulas, and gallstone ileus. Imaging findings and limitations of US, CT, MRI, and ERCP will be discussed. The review article will also briefly discuss the management of each disease. The presence of gallstones beyond the level of the cystic duct can lead to a spectrum of diseases, and emergency radiologists play a critical role in disease management by providing a timely diagnosis. Documenting the location of a gallstone within the common bile duct (CBD) in symptomatic cholelithiasis and the presence of acute interstitial edematous pancreatitis and/or ascending cholangitis plays a pivotal role in disease management. Establishing the presence of ectopic gallstones and biliary-enteric fistulae has a significant role in directing patient management.

Tran|Andrew|A| Hoff|Carrie|C| Polireddy|Karunesh|K| Neymotin|Arie|A| Maddu|Kiran|K|

Complications Emergency Gallstone Radiology


Assessing the effectiveness and implementation of a chronic disease self-management programme in faith-based organisations in Barbados: protocol for a cluster randomised parallel trial.

Abstract:
INTRODUCTION
In the COVID-19 environment of reduced patient interaction with the healthcare system, evidenced-based self-care of chronic disease is vital. We will evaluate the effect of an online chronic disease self-management programme (CDSMP) plus medication adherence tools on systolic blood pressure (SBP) (primary aim) and, seek to understand the barriers and facilitators to implementation of this modified CDSMP in faith-based organisations (FBOs) (secondary aim).

METHODS
We will conduct an unblinded cluster randomised trial in FBOs throughout Barbados. Eligibility: Persons ages 35-70 years; a previous diagnosis of hypertension or currently on antihypertensive therapy and the occurrence of two or more blood pressure readings above 130 mm Hg (systolic) or 80 mm Hg (diastolic) on the day of recruitment. Persons not known to have hypertension but who have two or more blood pressure readings at or above 130 mm Hg (systolic) or 80 mm Hg (diastolic) on two recruitment days at least 1 week apart will also be eligible. The unit of randomisation is a church cluster which consists of 7-9 churches. We will perform block randomisation to assign 24 clusters to intervention or control. The intervention has three components: modified CDSMP workshops, distribution of medication pill boxes and use of social media (WhatsApp V.2.0) to encourage medication adherence. Controls will receive one didactic lecture only. We will determine the mean changes in SBP levels for the intervention group versus controls and compare differences in outcomes 6 months' post intervention using mixed effects regression models.

ETHICS AND DISSEMINATION
This project has received ethical approval from the Institutional Review Board of the University of the West Indies in Barbados. Dissemination will use peer-reviewed publications, policy briefs to government and guidelines to leaders of FBOs. We aim to increase the proportion of patients with controlled hypertension and inform implementation of self-management programmes in small populations.

TRAIL REGISTRATION NUMBER
NCT04437966.

D016032:Randomized Controlled Trials as Topic

hypertension
clinical trials
preventive medicine
public health


Bipolar disorder and the gut microbiome: A systematic review.

Abstract:
OBJECTIVES
The microbiome is a rapidly advancing biomedical frontier with relevance for psychiatric illness. The gut microbiota interact with the central nervous system bidirectionally through the gut-brain axis and generate substances that may influence host metabolism, including short-chain fatty acids such as butyrate. Understanding gut microbiota in bipolar disorder (BD) may suggest new disease markers and treatment approaches.

METHODS
A PubMed search was performed on January 7, 2020 using terms "bipolar AND (microbiome OR microbiota)", for articles in English in which the study population included a distinct BD group and the gut microbiota/microbiome was assessed.

RESULTS
Thirteen articles met the inclusion criteria. In four of five studies that reported on group comparisons with respect to diversity, lower α-diversity was observed in BD relative to healthy controls (HC). The most convergent taxonomic finding was that in four studies, one particular clade distinguished gut microbiota between BD and HC: family Ruminococcaceae, genus Faecalibacterium, and species Faecalibacterium prausnitzii. Members of this clade, known for butyrate production, were reduced in BD relative to HC in three studies but elevated in a fourth. Additionally, genera Bacteroides or Bacteroides-Prevotella group species were elevated in BD in two studies but lower in a third.

CONCLUSIONS
Despite few studies and modest sample sizes, salient findings suggest that low α-diversity and dysbiosis with respect to abundance of Faecalibacterium and Bacteroides may characterize BD in both a trait and state-dependent fashion. Decreased richness and butyrate production also foster inflammation, which may be a hitherto unrecognized part of the pathophysiology underlying BD.

bipolar disorder
Faecalibacterium
inflammation
gastrointestinal microbiota/microbiome


Combined-Indications Significance Level of Multiple Related Indications Developed Simultaneously.

Abstract:
BACKGROUND
Typically, regulatory requirements include 2 confirmatory studies, each at a 1-sided .025 significance level, for a medicine to be approved for a specific indication. When the same medicine has been approved in related indications, 1 confirmatory study at a 1-sided .025 significance level could constitute adequate evidence of efficacy for a new indication.

METHODS
This article does not contain any studies with human or animal subjects performed by any of the authors. For multiple related indications developed simultaneously to constitute sufficient evidence of clinical efficacy, the combined-studies significance level can be set at the same level as if those indications are developed sequentially.

RESULTS
This article establishes possible strategies to develop a few related indications at the same time for marketing registration approval, maintaining a desired combined-studies significance level; for example, 1-sided .0000156 for 2 indications, with 1 option having each indication assessed with 1 confirmatory study at .00395 significance level.

CONCLUSION
It is possible to develop a few indications at the same time for marketing registration approval, where the combinedstudies significance level is less stringent than that of the usual paradigm with 2 confirmatory studies each at 1-sided .025 significance level for every indication.

Yuan|Jiacheng|J|0000-0002-2762-242X Zhu|Ray|R| Jia|Daniel|D| Palm|Ulo|U| Koch|Gary|G|

confirmatory studies
combined-studies significance level
combined-studies evidence
strength borrowing


Obesity and vitamin D deficiency: a systematic review and meta-analysis.

Abstract: Over the past decade, there have been an increasing number of studies on the association between vitamin D deficiency and anthropometric state. However, we did not identify any meta-analyses of the relationship between obesity and vitamin D deficiency in different age groups. Thus, we evaluated the association between obesity and vitamin D deficiency. We searched for observational studies published up to April 2014 in PubMed/Medline, Web of Science and Scopus databases. We performed a meta-analysis in accordance with the random-effects model to obtain the summary measurement (prevalence ratio, PR). Among the 29,882 articles identified, 23 met the inclusion criteria. The prevalence of vitamin D deficiency was 35% higher in obese subjects compared to the eutrophic group (PR: 1.35; 95% CI: 1.21-1.50) and 24% higher than in the overweight group (PR: 1.24; 95% CI: 1.14-1.34). These results indicate that the prevalence of vitamin D deficiency was more elevated in obese subjects. The vitamin D deficiency was associated with obesity irrespective of age, latitude, cut-offs to define vitamin D deficiency and the Human Development Index of the study location.

Pereira-Santos|M|M|
Costa|P R F|PR|
Assis|A M O|AM|
Santos|C A S T|CA|
Santos|D B|DB|

obesity
vitamin D deficiency
meta-analysis
25-hydroxy vitamin D


Automated multi-subject fiber clustering of mouse brain using dominant sets.

Abstract: Mapping of structural and functional connectivity may provide deeper understanding of brain function and disfunction. Diffusion Magnetic Resonance Imaging (DMRI) is a powerful technique to non-invasively delineate white matter (WM) tracts and to obtain a three-dimensional description of the structural architecture of the brain. However, DMRI tractography methods produce highly multi-dimensional datasets whose interpretation requires advanced analytical tools. Indeed, manual identification of specific neuroanatomical tracts based on prior anatomical knowledge is time-consuming and prone to operator-induced bias. Here we propose an automatic multi-subject fiber clustering method that enables retrieval of group-wise WM fiber bundles. In order to account for variance across subjects, we developed a multi-subject approach based on a method known as Dominant Sets algorithm, via an intra- and cross-subject clustering. The intra-subject step allows us to reduce the complexity of the raw tractography data, thus obtaining homogeneous neuroanatomically-plausible bundles in each diffusion space. The cross-subject step, characterized by a proper space-invariant metric in the original diffusion space, enables the identification of the same WM bundles across multiple subjects without any prior neuroanatomical knowledge. Quantitative analysis was conducted comparing our algorithm with spectral clustering and affinity propagation methods on synthetic dataset. We also performed qualitative analysis on mouse brain tractography retrieving significant WM structures. The approach serves the final goal of detecting WM bundles at a population level, thus paving the way to the study of the WM organization across groups.

Dodero|Luca|L| Vascon|Sebastiano|S| Murino|Vittorio|V| Bifone|Angelo|A| Gozzi|Alessandro|A| Sona|Diego|D|

multi-subject
clustering
dominant sets
diffusion magnetic resonance imaging
white matter
tractography
DTI
fibers segmentation


EFFICACY AND SAFETY OF A SINGLE-PILL COMBINATION OF ATORVASTATIN/AMLODIPINE IN PATIENTS WITH ARTERIAL HYPERTENSION AND DYSLIPIDEMIA.

Abstract: - The aim was to evaluate the efficacy of a single-pill combination of atorvastatin/amlodipine in patients with arterial hypertension, dyslipidemia and moderate to high cardiovascular risk. This prospective study included 243 patients with arterial hypertension, dyslipidemia and moderate to high cardiovascular risk, mean age 63.3±9.8 years. All patients were prescribed a treatment with one of the following doses of a single-pill combination of atorvastatin/amlodipine: 10/5, 10/10, 20/5 or 20/10 mg daily. The follow-up period was 3 months. The mean baseline values of the systolic and diastolic blood pressure were 155.7±16.2 and 92.0±9.2 mm Hg, respectively. At month 3, the respective mean systolic and diastolic blood pressure values were 136.9±26.9 and 80.6±5.1 mm Hg. The mean baseline values of total cholesterol and low-density lipoprotein cholesterol were 6.6±1.2 and 4.4±1.1 mmol/L, respectively. At month 3, the respective mean values of total cholesterol and low-density lipoprotein cholesterol were 5.1±0.9 and 2.9±1.0 mmol/L. Treatment was discontinued in 9 (3.7%) patients due to adverse events. In conclusion, treatment with the single-pill combination of atorvastatin/amlodipine was effective and well tolerated by the patients with arterial hypertension, dyslipidemia and moderate to high cardiovascular risk.

Naydenov Naydenov|Stefan|S|
Margaritov Runev|Nikolay|N|
Ivanov Manov|Emil|E|
Georgieva Torbova-Gigova|Svetla|S|

Hypertension
Dyslipidemias
Antihypertensive agents
Cardiovascular diseases


Assessing the environmental sustainability of ethanol from integrated biorefineries.

Abstract: This paper considers the life cycle environmental sustainability of ethanol produced in integrated biorefineries together with chemicals and energy. Four types of second-generation feedstocks are considered: wheat straw, forest residue, poplar, and miscanthus. Seven out of 11 environmental impacts from ethanol are negative, including greenhouse gas (GHG) emissions, when the system is credited for the co-products, indicating environmental savings. Ethanol from poplar is the best and straw the worst option for most impacts. Land use change from forest to miscanthus increases the GHG emissions several-fold. For poplar, the effect is opposite: converting grassland to forest reduces the emissions by three-fold. Compared to fossil and first-generation ethanol, ethanol from integrated biorefineries is more sustainable for most impacts, with the exception of wheat straw. Pure ethanol saves up to 87% of GHG emissions compared to petrol per MJ of fuel. However, for the current 5% ethanol-petrol blends, the savings are much smaller (<3%). Therefore, unless much higher blends become widespread, the contribution of ethanol from integrated biorefineries to the reduction of GHG emissions will be insignificant. Yet, higher ethanol blends would lead to an increase in some impacts, notably terrestrial and freshwater toxicity as well as eutrophication for some feedstocks.

Falano|Temitope|T|
Jeswani|Harish K|HK|
Azapagic|Adisa|A|

Ethanol
Integrated biorefineries
Environmental impacts
Biofuels
Life cycle assessment


Coexistence of myeloproliferative neoplasm and plasma-cell dyscrasia.

Abstract:
INTRODUCTION
Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), and are characterized by clonal proliferation of hematopoietic cells in the bone marrow. There are numerous case reports and reviews reporting patients with coexisting MPN and plasma-cell disease such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).

METHODS
We report 15 patients treated at our institution over a 5-year period (January 2008 to December 2012) with a diagnosis of both an MPN and MGUS or MM. We also reviewed and summarized published case reports and studies describing the coexistence of these two disease entities.

RESULTS
Most patients (12/15) had an MPN diagnosis made before or at the same time as the MGUS/MM diagnosis. Eventually, 2 patients developed a lymphoid leukemia, 1 patient developed lymphoma, and 1 patient developed acute myeloid leukemia, raising the question of whether patients with coexistence of myeloid- and lymphoid-derived neoplasms are more prone to leukemic or lymphomatous transformation. We did not find any treatment-related effect that could have contributed to the development of coexisting MGUS or MM and MPN. Of the 7 patients with an abnormal karyotype, 3 patients had trisomy 8.

CONCLUSION
At present, management strategies are aimed at treating the MPN and regularly monitoring the MGUS for transformation to an overt plasma-cell malignancy. However, for patients who develop overt MM, management is focused more on treating the myeloma and monitoring the MPN. It has not yet been definitively shown that these 2 entities arise from a common-ancestor hematopoietic stem cell.

Malhotra|Jyoti|J| Kremyanskaya|Marina|M| Schorr|Emily|E| Hoffman|Ronald|R| Mascarenhas|John|J|

Myeloproliferative neoplasm
Polycythemia vera
Essential thrombocythemia
Myelofibrosis
MGUS


Updating the research on the chemopreventive and therapeutic role of the peptide lunasin.

Abstract: Chronic diseases have become the medical challenge of the 21st century because of their high incidence and mortality rates. Modulation of diet and lifestyle habits is considered as the best strategy for the prevention of these disorders. Health promoting benefits beyond their nutritional effects have been described for multiple dietary compounds. Among these compounds, the peptide lunasin is considered as one of the most promising. Naturally present in soybean, lunasin has been extensively studied in the last two decades because of its potential against chronic diseases such as cancer, cardiovascular and immunological disorders. The purpose of this article is to summarise the evidence on the presence of lunasin in soybean and derived foods, and its bioavailability once it is orally ingested. The protective and therapeutic effects of this peptide against cancer, oxidative stress, inflammation, and high cholesterol levels as well as the molecular mechanisms of action involved in these effects are also described in this review. © 2017 Society of Chemical Industry.

chemopreventive and therapeutic properties


Tinnitus Treatment with Oxytocin: A Pilot Study.

Abstract:
INTRODUCTION
Tinnitus is the perception of sound in the absence of an external stimulus. It is a frequent condition for which there is as yet no pharmacological treatment approved. Auditory and non-auditory pathways are involved in tinnitus' pathophysiology. Oxytocin is a neurohormone and eventual neurotransmitter that plays a complex role in social cognition and behavior.

OBJECTIVE
To evaluate the potential of oxytocin as a tinnitus treatment.

STUDY DESIGN
Two studies were performed. Study 1 was a long-term open pilot study, while study 2 investigated short-term effects with a double-blinded placebo-controlled cross-over study.

SETTING
Ambulatory ENT care.

SUBJECTS AND METHOD
In study 1, 15 patients were investigated over a 10-week period in an open pilot study. In study 2, 16 patients were included in a placebo-controlled crossover trial to investigate short-term effects following a single dose.

RESULTS
For the long-term study (study 1), analysis of variance revealed a significant decrease in tinnitus sensation, both for the Tinnitus Handicap Inventory and Clinical Global Impression (CGI). Also, the short-term effects in study 2 revealed a significant reduction of tinnitus because of the oxytocin nasal spray as measured with the Visual Analog Scale and the CGI Scale.

CONCLUSION
These preliminary studies demonstrated that oxytocin may represent a helpful tool for treating tinnitus and further larger controlled studies are warranted.

Azevedo|Andreia Aparecida|AA|
Figueiredo|Ricardo Rodrigues|RR|
Elgoyhen|Ana Belen|AB|
Langguth|Berthold|B|
Penido|Norma De Oliveira|NO|
Schlee|Winfried|W|

tinnitus
oxytocin
nasal sprays
hearing disorders
pharmacotherapy


The introduction of hospital networks in Belgium: The path from policy statements to the 2019 legislation.

Abstract: In April 2015, the Belgian Federal Minister for Social Affairs and Public Health launched an Action Plan to reform the hospital landscape. With the creation of "localregional clinical hospital networks" with their own governance structures, the plan follows the international trend towards hospital consolidation and collaboration. The major complicating factors in the Belgian context are (1) that policy instruments for the redesign of the hospital service delivery system are divided between the federal government and the federated authorities, which can result in an asymmetric hospital landscape with a potentially better distribution of clinical services in the Flanders hospital collaborations than in the other federated entities; and (2) the current regulations stipulate that only hospitals (and not networks) are entitled to hospital budgets. Although the reform is the most significant and drastic transformation of the Belgian hospital sector in the last three decades, networks mainly offer a framework in which hospitals can collaborate. More regulation and policy measures are needed to enhance collaboration and distribution of clinical services.

De Regge|Melissa|M|
De Pourcq|Kaat|K|
Van de Voorde|Carine|C|
Van den Heede|Koen|K|
Gemmel|Paul|P|
Eeckloo|Kristof|K|

D001530:Belgium
D003695:Delivery of Health Care
D004469:Economics, Hospital
D018166:Health Care Reform
D006291:Health Policy
D006801:Humans
D007882:Legislation, Hospital

Hospitals Reform Governance Collaboration


Sweet Taste-Sensing Receptors Expressed in Pancreatic β-Cells: Sweet Molecules Act as Biased Agonists.

Abstract: The sweet taste receptors present in the taste buds are heterodimers comprised of T1R2 and T1R3. This receptor is also expressed in pancreatic β-cells. When the expression of receptor subunits is determined in β-cells by quantitative reverse transcription polymerase chain reaction, the mRNA expression level of T1R2 is extremely low compared to that of T1R3. In fact, the expression of T1R2 is undetectable at the protein level. Furthermore, knockdown of T1R2 does not affect the effect of sweet molecules, whereas knockdown of T1R3 markedly attenuates the effect of sweet molecules. Consequently, a homodimer of T1R3 functions as a receptor sensing sweet molecules in β-cells, which we designate as sweet taste-sensing receptors (STSRs). Various sweet molecules activate STSR in β-cells and augment insulin secretion. With regard to intracellular signals, sweet molecules act on STSRs and increase cytoplasmic Ca(2+) and/or cyclic AMP (cAMP). Specifically, when an STSR is stimulated by one of four different sweet molecules (sucralose, acesulfame potassium, sodium saccharin, or glycyrrhizin), distinct signaling pathways are activated. Patterns of changes in cytoplasmic Ca(2+) and/or cAMP induced by these sweet molecules are all different from each other. Hence, sweet molecules activate STSRs by acting as biased agonists.

Kojima|Itaru|I| Nakagawa|Yuko|Y| Ohtsu|Yoshiaki|Y| Medina|Anya|A| Nagasawa|Masahiro|M|

β-Cell
Biased agonist
Sweet taste receptor
Insulin
Cyclic AMP
Calcium


Versican in the Tumor Microenvironment.

Abstract: Versican is an extracellular matrix proteoglycan with nonredundant roles in diverse biological and cellular processes, ranging from embryonic development to adult inflammation and cancer. Versican is essential for cardiovascular morphogenesis, neural crest migration, and skeletal development during embryogenesis. In the adult, versican acts as an inflammation "amplifier" and regulator of immune cell activation and cytokine production. Increased versican expression has been observed in a wide range of malignant tumors and has been associated with poor patient outcomes. The main sources of versican production in the tumor microenvironment include accessory cells (myeloid cells and stromal components) and, in some contexts, the tumor cells themselves. Versican has been implicated in several classical hallmarks of cancer such as proliferative signaling, evasion of growth suppressor signaling, resistance to cell death, angiogenesis, and tissue invasion and metastasis. More recently, versican has been implicated in escape from tumor immune surveillance, e.g., through dendritic cell dysfunction. Versican's multiple contributions to benign and malignant biological processes are further diversified through the generation of versican-derived bioactive proteolytic fragments (matrikines), with versikine being the most studied to date. Versican and versican-derived matrikines hold promise as targets in the management of inflammatory and malignant conditions as well as in the development of novel predictive and prognostic biomarkers.

Versican
Tumor microenvironment
Proteoglycans
Inflammation
Metastasis
Dendritic cells
Versikine
Biomarkers
ADAMTS
Immunotherapy
Macrophages
Myeloid regulatory cells
Tumor matrix
Tumor progression
Versican proteolysis


Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells.

Abstract:
OBJECTIVE
To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells.

METHODS
C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 µM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 µM fluoxetine, and the expression of Bcl-xL protein was measured using western blot.

RESULTS
As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsα and Bcl-xL) and down-regulated 77 genes (including Gαi2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsα mRNA and a decrease in Gαi2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased.

CONCLUSION
These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsα expression but also induces Bcl-xL expression, thus inhibiting apoptosis.

Choi|Mi Ran|MR|
Oh|Dong Hoon|DH|
Kim|Seok Hyeon|SH|
Yang|Byung-Hwan|BH|
Lee|Jun-Seok|JS|
Choi|Joonho|J|
Jeon|Hyun-Soo|HS|
Chai|Young Gyu|YG|
Park|Yong-Chon|YC|

Fluoxetine Bcl-xL Microarray Gsα Gαi2 Antidepressant


The Essex-Lopresti Injury:: Evaluation and Treatment Considerations.

Abstract: This article describes evaluation and treatment considerations for Essex-Lopresti injuries. Specific information about pattern recognition and treatment options is provided.

D006801:Humans
D000080944:Interosseous Membrane
D004204:Joint Dislocations
D011885:Radius Fractures
D014954:Wrist Injuries

Essex-Lopresti
Axial instability of the forearm
Longitudinal instability of the forearm


Effect of Metal Ion Intercalation on the Structure of MXene and Water Dynamics on its Internal Surfaces.

Abstract: MXenes are a recently discovered class of 2D materials with an excellent potential for energy storage applications. Because MXene surfaces are hydrophilic and attractive interaction forces between the layers are relatively weak, water molecules can spontaneously intercalate at ambient humidity and significantly influence the key properties of this 2D material. Using complementary X-ray and neutron scattering techniques, we demonstrate that intercalation with potassium cations significantly improves structural homogeneity and water stability in MXenes. In agreement with molecular dynamics simulations, intercalated potassium ions reduce the water self-diffusion coefficient by 2 orders of magnitude, suggesting greater stability of hydrated MXene against changing environmental conditions.

Osti|Naresh C|NC|
Naguib|Michael|M|
Ostadhossein|Alireza|A|
Xie|Yu|Y|
Kent|Paul R C|PR|
Dyatkin|Boris|B|
Rother|Gernot|G|
Heller|William T|WT|
van Duin|Adri C T|AC|
Gogotsi|Yury|Y|
Mamontov|Eugene|E|

intercalation
MXenes
ReaxFF simulation
quasi-elastic neutron scattering
water diffusion


Exogenous Melatonin Suppresses Dark-Induced Leaf Senescence by Activating the Superoxide Dismutase-Catalase Antioxidant Pathway and Down-Regulating Chlorophyll Degradation in Excised Leaves of Perennial Ryegrass (Lolium perenne L.).

Abstract: Leaf senescence is a typical symptom in plants exposed to dark and may be regulated by plant growth regulators. The objective of this study was to determine whether exogenous application of melatonin (N-acetyl-5-methoxytryptamine) suppresses dark-induced leaf senescence and the effects of melatonin on reactive oxygen species (ROS) scavenging system and chlorophyll degradation pathway in perennial grass species. Mature perennial ryegrass (Lolium perenne L. cv. 'Pinnacle') leaves were excised and incubated in 3 mM 2-(N-morpholino) ethanesulfonic buffer (pH 5.8) supplemented with melatonin or water (control) and exposed to dark treatment for 8 days. Leaves treated with melatonin maintained significantly higher endogenous melatonin level, chlorophyll content, photochemical efficiency, and cell membrane stability expressed by lower electrolyte leakage and malondialdehyde (MDA) content compared to the control. Exogenous melatonin treatment also reduced the transcript level of chlorophyll degradation-associated genes and senescence marker genes (LpSAG12.1, Lph36, and Lpl69) during the dark treatment. The endogenous O2- production rate and H2O2 content were significantly lower in these excised leaves treated with melatonin compared to the water control. Exogenous melatonin treatment caused increases in enzymatic activity and transcript levels of superoxide dismutase and catalase but had no significant effects on ascorbate peroxidase, glutathione reductase, dehydroascorbate reductase, and monohydroascorbate reductase. The content of non-enzymatic antioxidants, such as ascorbate and dehydroascorbate, were decreased by melatonin treatment, while the content of glutathione and oxidized glutathione was not affected by melatonin. These results suggest that the suppression of dark-induced leaf senescence by exogenous melatonin may be associated with its roles in regulating ROS scavenging through activating the superoxide dismutase-catalase enzymatic antioxidant pathway and down-regulating chlorophyll degradation in perennial ryegrass.

Zhang|Jing|J| Li|Huibin|H| Xu|Bin|B| Li|Jing|J| Huang|Bingru|B|

melatonin
leaf senescence
antioxidant
chlorophyll degradation
reactive oxygen species


Critical appraisal of the quality of clinical practice guidelines for idiopathic pulmonary fibrosis.

Abstract:
Background
Clinical practice guidelines (CPGs) have long served as an essential tool for clinicians to rationalize their treatment in practice. However, the quality of guidelines varies greatly. The present study aimed to analyze high-quality CPGs of idiopathic pulmonary fibrosis (IPF) and highlight the potential for further improvement.

Methods
Three guideline developers' websites, PubMed, Embase, and Web of Science, as well as a public search engine, Google Scholar, were searched to retrieve CPGs regarding the management of IPF. The methodology and reporting quality of retrieved CPGs were assessed using the validated Appraisal of Guidelines for Research and Evaluation Instrument II (AGREE II) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist.

Results
Twelve IPF CPGs were reviewed, among which 7 (58.3%) were considered as "recommended" and 1 (8.3%) as "recommended with modifications". Among the 6 domains of AGREE II, scope and purpose (70.99%) and clarity of presentation (68.06%) were considered to be the fields in which CPGs performed best, evidenced by the highest mean AGREE II scores. The domains in which the reviewed CPGs received the lowest mean scores were rigor of development (50.87%) and applicability (34.14%). The intraclass correlation coefficient scores were excellent in each domain. The basic information domain received the highest overall reporting rate in the 7 domains of the RIGHT checklist; the other 6 domains had a full reporting rate of <50%. Eight items had a satisfactory level of reporting, whereas 14 items had poor reporting according to the RIGHT checklist. Correlation analysis revealed a highly positive correlation between the methodology and reporting quality of CPGs for IPF (r=0.872).

Conclusions
The methodological quality of selected IPF CPGs fluctuated greatly, and the full reporting rate was found to be quite low in some domains. In the future, we should focus not only on improving the methodological quality in the development of guidelines, but also on the reporting quality of guidelines.

Li|Xuanlin|X| Yu|Xueqing|X| Xie|Yang|Y| Feng|Zhenzhen|Z| Ma|Yanfang|Y| Chen|Yaolong|Y| Li|Jiansheng|J|

Reporting Items for Practice Guidelines in Healthcare checklist (RIGHT checklist)


Primary Cutaneous Mucormycosis Caused by Rhizopus oryzae: A Case Report and Review of Literature.

Abstract: Mucormycosis is an invasive infection caused by opportunistic fungi. Rhizopus, Lichtheimia, Mucor and Rhizomucor are the most common isolated genera. Primary cutaneous mucormycosis is usually related to traumatic injuries, but immunocompromised cases are associated with underlying conditions such as diabetes mellitus and malignancies. The treatment of choice is surgical debridement and liposomal amphotericin B. We present a 40-year-old male with fever and a painful necrotic lesion on the middle back and history of poorly controlled diabetes mellitus. Rhizopus oryzae was isolated and identified using an internal transcribed spacer regions ITS1 and ITS2. An initial good response to treatment was observed; however, 7 days later a diabetic ketoacidosis due to poor adherence to treatment caused a lethal outcome.

Rodríguez-Lobato|Erika|E|
Ramírez-Hobak|Lourdes|L|
Aquino-Matus|Jorge E|JE|
Ramírez-Hinojosa|Juan P|JP|
Lozano-Fernández|Víctor H|VH|
Xicohtencatl-Cortes|Juan|J|
Hernández-Castro|Rigoberto|R|
Arenas|Roberto|R|

Primary cutaneous mucormycosis
Rhizopus oryzae
Opportunistic fungal infection


Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments.

Abstract: During mammalian embryonic development, primary cilia transduce and regulate several signaling pathways. Among the various pathways, Sonic hedgehog (SHH) is one of the most significant. SHH signaling remains quiescent in adult mammalian tissues. However, in multiple adult tissues, it becomes active during differentiation, proliferation, and maintenance. Moreover, aberrant activation of SHH signaling occurs in cancers of the skin, brain, liver, gallbladder, pancreas, stomach, colon, breast, lung, prostate, and hematological malignancies. Recent studies have shown that the tumor microenvironment or stroma could affect tumor development and metastasis. One hypothesis has been proposed, claiming that the pancreatic epithelia secretes SHH that is essential in establishing and regulating the pancreatic tumor microenvironment in promoting cancer progression. The SHH signaling pathway is also activated in the cancer stem cells (CSC) of several neoplasms. The self-renewal of CSC is regulated by the SHH/Smoothened receptor (SMO)/Glioma-associated oncogene homolog I (GLI) signaling pathway. Combined use of SHH signaling inhibitors and chemotherapy/radiation therapy/immunotherapy is therefore key in targeting CSCs.

D002528:Cerebellar Neoplasms
D005706:Gallbladder Neoplasms
D053823:Hedgehog Proteins
D006801:Humans
D008113:Liver Neoplasms
D008527:Medulloblastoma
D009369:Neoplasms
D014411:Neoplastic Stem Cells
D009389:Neovascularization, Pathologic
D018919:Neovascularization, Physiologic
D038081:Organogenesis
D010190:Pancreatic Neoplasms
D015398:Signal Transduction
D059016:Tumor Microenvironment


Effect of Intermittent Hypoxia Training for Dizziness: A Randomized Controlled Trial.

Abstract:
OBJECTIVE
To study the effect of intermittent hypoxia training (IHT) for dizziness.

DESIGN
A single-blind, randomized controlled trial. All participants were recruited from a rehabilitation department in an acute university-affiliated hospital.

INTERVENTION
Participants with dizziness were randomly assigned to 2 groups (IHT group and control group). The Dizziness Handicap Inventory, Activities-specific Balance Confidence Scale, and Vertigo Visual Analog Scale were conducted at baseline, end of the fourth week.

RESULTS
Among 52 subjects, there were18 males and 34 females, ages 35 to 62 years old (mean [SD] = 46.9 [7.93]). Time length since onset ranged from 12 to 34 months (20.2 [7.15] mo). Dizziness Handicap Inventory, Activities-specific Balance Confidence Scale, Vertigo Visual Analog Scale scores, and attack frequencies of dizziness were improved after IHT intervention in the end of the fourth week. There were significant differences between the IHT group and the control group in the Dizziness Handicap Inventory, Activities-specific Balance Confidence Scale, Vertigo Visual Analog Scale scores, and attack frequencies of dizziness at the end of the fourth week (P < .05). No adverse events occurred during the study.

CONCLUSION
IHT could improve dizziness after intervention at the end of the fourth week. IHT could be the effective method for treating dizziness.

Bao|Xiao|X| Tan|Jie-Wen|JW| Long|Ying|Y| Liu|Howe|H| Liu|Hui-Yu|HY|

intermittent hypoxia training
dizziness
vascular function


Longitudinal Study of the Variation in Patient Turnover and Patient-to-Nurse Ratio: Descriptive Analysis of a Swiss University Hospital.

Abstract:
BACKGROUND
Variations in patient demand increase the challenge of balancing high-quality nursing skill mixes against budgetary constraints. Developing staffing guidelines that allow high-quality care at minimal cost requires first exploring the dynamic changes in nursing workload over the course of a day.

OBJECTIVE
Accordingly, this longitudinal study analyzed nursing care supply and demand in 30-minute increments over a period of 3 years. We assessed 5 care factors: patient count (care demand), nurse count (care supply), the patient-to-nurse ratio for each nurse group, extreme supply-demand mismatches, and patient turnover (ie, number of admissions, discharges, and transfers).

METHODS
Our retrospective analysis of data from the Inselspital University Hospital Bern, Switzerland included all inpatients and nurses working in their units from January 1, 2015 to December 31, 2017. Two data sources were used. The nurse staffing system (tacs) provided information about nurses and all the care they provided to patients, their working time, and admission, discharge, and transfer dates and times. The medical discharge data included patient demographics, further admission and discharge details, and diagnoses. Based on several identifiers, these two data sources were linked.

RESULTS
Our final dataset included more than 58 million data points for 128,484 patients and 4633 nurses across 70 units. Compared with patient turnover, fluctuations in the number of nurses were less pronounced. The differences mainly coincided with shifts (night, morning, evening). While the percentage of shifts with extreme staffing fluctuations ranged from fewer than 3% (mornings) to 30% (evenings and nights), the percentage within "normal" ranges ranged from fewer than 50% to more than 80%. Patient turnover occurred throughout the measurement period but was lowest at night.

CONCLUSIONS
Based on measurements of patient-to-nurse ratio and patient turnover at 30-minute intervals, our findings indicate that the patient count, which varies considerably throughout the day, is the key driver of changes in the patient-to-nurse ratio. This demand-side variability challenges the supply-side mandate to provide safe and reliable care. Detecting and describing patterns in variability such as these are key to appropriate staffing planning. This descriptive analysis was a first step towards identifying time-related variables to be considered for a predictive nurse staffing model.

D010561:Personnel Staffing and Scheduling

workload
nurse staffing
electronic health records
patient safety
routine data


Development and Validation of a Smartphone-based Contrast Sensitivity Test.

Abstract:
Purpose
Contrast sensitivity (CS) testing is an important measure of visual function reflecting variations in everyday visual experience in different conditions and helps to identify more subtle vision loss. However, it is only infrequently used. To make this more accessible, we have developed and validated a smartphone-based CS test.

Methods
A new tumbling-E smartphone-based CS test was developed, Peek Contrast Sensitivity (PeekCS). This was field tested and refined through several iterations. Reference standard was a tumbling-E Pelli-Robson CS test (PRCS). The validation study was conducted in community clinics in Ethiopia. Test-retest variability was measured for both PRCS and PeekCS. PRCS and PeekCS were then compared. Correlation coefficients and 95% confidence intervals (CIs) were calculated; 95% limits of agreement were calculated and displayed on Bland-Altman plots.

Results
PeekCS showed strong repeatability (correlation coefficient: 0.93; 95% CI: 0.91-0.95), which was comparable with PRCS (correlation coefficient: 0.96; 95% CI: 0.95-0.97). The 95% limit of agreement for test-retest variability of PRCS and PeekCS were -0.20 to 0.21 and -0.31 to 0.29, respectively. PRCS and PeekCS were highly correlated: 0.94 (95% CI: 0.93-0.95); 95% limits of agreement -0.27 to 0.29; and mean difference 0.010 (95% CI: -0.001 to 0.022). PeekCS had a faster testing time (44.6 seconds) than PRCS (48.6 seconds): mean difference -3.98 (95% CI: -5.38 to -2.58); P < 0.001.

Conclusions
The smartphone-based PeekCS is a repeatable and rapid test, providing results that are highly comparable with the commonly used PRCS test.

Translational Relevance
PeekCS provides an accessible and easy to perform alternative for CS testing, particularly in the community setting.

Habtamu|Esmael|E|
Bastawrous|Andrew|A|
Bolster|Nigel M|NM|
Tadesse|Zerihun|Z|
Callahan|E Kelly|EK|
Gashaw|Bizuayehu|B|
Macleod|David|D|
Burton|Matthew J|MJ|

contrast sensitivity
smartphone
trachoma


Rational design of α-Fe2O3 nanocubes supported BiVO4 Z-scheme photocatalyst for photocatalytic degradation of antibiotic under visible light.

Abstract: The Z-scheme BiVO4/α-Fe2O3 photocatalyst was synthesized by a simple hydrothermal method. The photocatalyst is composed of α-Fe2O3 nanocubes with a regular cubic structure and the BiVO4 particles distributed on the surface of the α-Fe2O3 nanocubes. The photocatalytic performance of Z-scheme BiVO4/α-Fe2O3 photocatalyst was investigated in terms of its capacity for photodegradation of tetracycline hydrochloride. Improved photocatalytic activity was observed for Z-scheme BiVO4/α-Fe2O3 photocatalyst compared with pure BiVO4 and α-Fe2O3 nanocubes under visible light irradiation. Studies of its morphology, physicochemical properties and photoelectrochemical behaviors demonstrated that BiVO4 loading on the surface of α-Fe2O3 nanocubes forms a Z-scheme heterojunction, which increases the specific surface area and significantly promotes the separation of photoinduced carriers. The main active species were determined to be OH and h+ by ESR technique and trapping experiments. We propose a possible photocatalytic mechanism of Z-scheme BiVO4/α-Fe2O3 photocatalyst system. This study may also provide a novel and eco-friendly demonstration of a useful strategy for the design and preparation of special structure photocatalytic materials.

Ma|Changchang|C|
Lee|Jeongwoo|J|
Kim|Youjoong|Y|
Cheol Seo|Won|W|
Jung|Hyun|H|
Yang|Woochul|W|

Nanocubes
Photocatalytic degradation
Tetracycline hydrochloride
Z-scheme heterojunction
BiVO(4)/α-Fe(2)O(3)


Congestive myeloradiculopathy in a patient with Cowden syndrome.

Abstract: We present a patient with newly diagnosed Cowden syndrome and congestive myeloradiculopathy secondary to spinal dural arteriovenous fistula (SDAVF). This patient illustrates the difficulties that can be encountered in diagnosing SDAVF and emphasises the need to pursue the diagnosis in the appropriate clinical setting, as treatment can lead to significant neurological improvement. To our knowledge this is also the first reported case of an association between Cowden syndrome and SDAVF.

Wu|Teddy Y|TY|
Willoughby|Ernest|E|
Hutchinson|David O|DO|
Brew|Stefan|S|
McGuinness|Ben|B|
Lopes|Rebecca|R|
Love|Donald R|DR|
Roxburgh|Richard H|RH|

D020785:Central Nervous System Vascular Malformations

Cowden syndrome
Dural arteriovenous fistula
Myelopathy


'Dignity therapy', a promising intervention in palliative care: A comprehensive systematic literature review.

Abstract:
BACKGROUND
Dignity therapy is psychotherapy to relieve psychological and existential distress in patients at the end of life. Little is known about its effect.

AIM
To analyse the outcomes of dignity therapy in patients with advanced life-threatening diseases.

DESIGN
Systematic review was conducted. Three authors extracted data of the articles and evaluated quality using Critical Appraisal Skills Programme. Data were synthesized, considering study objectives.

DATA SOURCES
PubMed, CINAHL, Cochrane Library and PsycINFO. The years searched were 2002 (year of dignity therapy development) to January 2016. 'Dignity therapy' was used as search term. Studies with patients with advanced life-threatening diseases were included.

RESULTS
Of 121 studies, 28 were included. Quality of studies is high. Results were grouped into effectiveness, satisfaction, suitability and feasibility, and adaptability to different diseases and cultures. Two of five randomized control trials applied dignity therapy to patients with high levels of baseline psychological distress. One showed statistically significant decrease on patients' anxiety and depression scores over time. The other showed statistical decrease on anxiety scores pre-post dignity therapy, not on depression. Nonrandomized studies suggested statistically significant improvements in existential and psychosocial measurements. Patients, relatives and professionals perceived it improved end-of-life experience.

CONCLUSION
Evidence suggests that dignity therapy is beneficial. One randomized controlled trial with patients with high levels of psychological distress shows DT efficacy in anxiety and depression scores. Other design studies report beneficial outcomes in terms of end-of-life experience. Further research should understand how dignity therapy functions to establish a means for measuring its impact and assessing whether high level of distress patients can benefit most from this therapy.

Martínez|Marina|M|
Arantzamendi|María|M|
Belar|Alazne|A|
Carrasco|José Miguel|JM|
Carvajal|Ana|A|
Rullán|María|M|
Centeno|Carlos|C|

D003376:Counseling
D006801:Humans
D010166:Palliative Care
D011614:Psychotherapy, Brief
D011788:Quality of Life
D013315:Stress, Psychological
D013727:Terminal Care
D019452:Terminally Ill

Dignity therapy
palliative care
psychotherapy
end of life
terminal


Compositional differences in soybeans on the market: glyphosate accumulates in Roundup Ready GM soybeans.

Abstract: This article describes the nutrient and elemental composition, including residues of herbicides and pesticides, of 31 soybean batches from Iowa, USA. The soy samples were grouped into three different categories: (i) genetically modified, glyphosate-tolerant soy (GM-soy); (ii) unmodified soy cultivated using a conventional "chemical" cultivation regime; and (iii) unmodified soy cultivated using an organic cultivation regime. Organic soybeans showed the healthiest nutritional profile with more sugars, such as glucose, fructose, sucrose and maltose, significantly more total protein, zinc and less fibre than both conventional and GM-soy. Organic soybeans also contained less total saturated fat and total omega-6 fatty acids than both conventional and GM-soy. GM-soy contained high residues of glyphosate and AMPA (mean 3.3 and 5.7 mg/kg, respectively). Conventional and organic soybean batches contained none of these agrochemicals. Using 35 different nutritional and elemental variables to characterise each soy sample, we were able to discriminate GM, conventional and organic soybeans without exception, demonstrating "substantial non-equivalence" in compositional characteristics for 'ready-to-market' soybeans.

Bøhn|T|T| Cuhra|M|M| Traavik|T|T| Sanden|M|M| Fagan|J|J| Primicerio|R|R|

Pesticides
Nutrition
Agricultural practice
GMO
Herbicide residues
Substantial equivalence


Cervical leverage: A new procedure to deliver deep retrosternal goitres without thoracotomy.

Abstract:
INTRODUCTION
Although most retrosternal goitres can be removed through a standard collar incision, some cases require extra-cervical incisions for complete resection. We report a new technique to remove large retrosternal goitres without extra-cervical incisions.

PRESENTATION OF CASE
We present two cases in which a US Army-Navy (Parker-Langenback) retractor was used to deliver large retrosternal components into the cervical incisions.

DISCUSSION
This technique is useful in cases where the retrosternal component extends beyond the reach of the exploring finger and a well-developed plane can be developed between the gland and surrounding tissue.

CONCLUSION
The cervical leverage technique allows removal of a large retrosternal component through a cervical incision, thereby avoiding the attendant morbidity of a thoracotomy or median sternotomy. It should not be used if there is suspected neoplastic disease, dense adherence to or invasion of surrounding intra-thoracic structures.

Naraynsingh|Vijay|V|
Ramarine|Ian|I|
Cawich|Shamir O|SO|
Maharaj|Ravi|R|
Dan|Dilip|D|

Retrosternal Goitre Thoracotomy Mediastinal Thyroid


Epitope mapping of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in a mouse model of multiple sclerosis: microwave-assisted synthesis of the peptide antigens and ELISA screening.

Abstract: The role of pathologic auto-antibodies against myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is a highly controversial matter. As the use of animal models may enable to unravel the molecular mechanisms of the human disorder, numerous studies on multiple sclerosis are carried out using experimental autoimmune encephalomyelitis (EAE). In particular, the most extensively used EAE model is obtained by immunizing C57BL/6 mice with the immunodominant peptide MOG(35-55). In this scenario, we analyzed the anti-MOG antibody response in this model using the recombinant refolded extracellular domain of the protein, MOG(1-117). To assess the presence of a B-cell intramolecular epitope spreading mechanism, we tested also five synthetic peptides mapping the 1-117 sequence of MOG, including MOG(35-55). For this purpose, we cloned, expressed in Escherichia coli and on-column refolded MOG(1-117), and we applied an optimized microwave-assisted solid-phase synthetic strategy to obtain the designed peptide sequences. Subsequently, we set up a solid-phase immunoenzymatic assay testing both naïve and EAE mice sera and using MOG protein and peptides as antigenic probes. The results obtained disclose an intense IgG antibody response against both the recombinant protein and the immunizing peptide, while no response was observed against the other synthetic fragments, thus excluding the presence of an intramolecular epitope spreading mechanism. Furthermore, as the properly refolded recombinant probe is able to bind antibodies with greater efficiency compared with MOG(35-55), we hypothesize the presence of both linear and conformational epitopes on MOG(35-55) sequence.


The identification and characterisation of autophagy inhibitors from the published kinase inhibitor sets.

Abstract: Autophagy is a critical cellular homeostatic mechanism, the dysfunction of which has been linked to a wide variety of disease states. It is regulated through the activity of specific kinases, in particular Unc-51 like autophagy activating kinase 1 (ULK1) and Phosphatidylinositol 3-kinase vacuolar protein sorting 34 (VPS34), which have both been suggested as potential targets for drug development. To identify new chemical compounds that might provide useful chemical tools or act as starting points for drug development, we screened each protein against the Published Kinase Inhibitor Set (PKIS), a library of known kinase inhibitors. In vitro screening and analysis of the published selectivity profiles of the hits informed the selection of three relatively potent ATP-competitive inhibitors against each target that presented the least number of off-target kinases in common. Cellular assays confirmed potent inhibition of autophagy in response to two of the ULK1 inhibitors and all three of the VPS34 inhibitors. These compounds represent not only a new resource for the study of autophagy but also potential chemical starting points for the validation or invalidation of these two centrally important autophagy kinases in disease models.

Zachari|Maria|M|
Rainard|Julie M|JM|
Pandarakalam|George C|GC|
Robinson|Lindsay|L|
Gillespie|Jonathan|J|
Rajamanickam|Muralikrishnan|M|
Hamon|Veronique|V|
Morrison|Angus|A|
Ganley|Ian G|IG|
McElroy|Stuart P|SP|

D058546:Class III Phosphatidylinositol 3-Kinases

D047908:Intracellular Signaling Peptides and Proteins

autophagy
kinases
chemical biology
high-throughput screening


Isoproterenol injected into the basolateral amygdala rescues amyloid β1-42-induced conditioned fear memory deficit via reducing intracellular Zn2+ toxicity.

Abstract: On the basis of amyloid β (Aβ) peptides as triggers in atrophy of structures in the limbic system, here we postulated that Aβ1-42-induced intracellular Zn2+ toxicity in the basolateral amygdala contributes to conditioned fear memory. Aβ1-42 increased intracellular Zn2+ level in the amygdala after local injection of Aβ1-42 into the basolateral amygdala, resulting in conditioned fear memory deficit via attenuated LTP at perforant pathway-basolateral amygdala synapses. Co-injection of isoproterenol, a beta-adrenergic receptor agonist, reduced Aβ1-42-mediated increase in intracellular Zn2+, resulting in rescue of the memory deficit and attenuated LTP. The present study suggests that beta-adrenergic activity induced by isoproterenol in the basolateral amygdala rescues the impairment of conditioned fear memory by Aβ1-42. The rescuing effect may be linked with reducing Aβ1-42-induced intracellular Zn2+ toxicity. Furthermore, Aβ1-42 injection into the basolateral amygdala also attenuated LTP at perforant pathway-dentate granule cell synapses, while co-injection of isoproterenol rescued it, suggesting that Aβ1-42 toxicity in the basolateral amygdala also affects hippocampus-dependent memory. It is likely that beta-adrenergic receptor activation in the basolateral amygdala rescues the limbic system exposed to Aβ1-42 toxicity.

Ishikawa|Yudai|Y| Itoh|Ryusei|R| Tsujimoto|Rin|R| Tamano|Haruna|H| Takeda|Atsushi|A|

Isoproterenol
Basolateral amygdala
Fear memory
Adrenergic β receptor
Amyloid β(1-42)
Zn(2+) dysregulation


Zebrafish as a model for studying the developmental neurotoxicity of propofol.

Abstract: Anesthetics can cause widespread apoptotic neurodegeneration and adverse effects on synaptogenesis during early postnatal life. Synaptogenesis correlates with several proteins, including myelin basic protein (MBP). However, little is known about the adverse effects of exposure to propofol on MBP, particularly during embryonic development. Our goal was to use zebrafish to explore the effect of propofol on embryonic development, apoptosis and MBP expression. Zebrafish embryos were exposed to propofol at defined doses and stages from 6 to 48 h postfertilization by immersion. The survival rate, hatchability, aberration rate, cell apoptosis and gene expression were analyzed at defined stages. Analysis revealed that doses of 1, 2 and 3 µg ml(-1) propofol were reasonable anesthetic concentrations for zebrafish embryos. These doses of propofol caused a significant decrease in hatchability and an increase in aberration rate. Moreover, 6 days postfertilization (dpf) larvae are anesthetized by immersion into water containing 1, 2 or 3 µg ml(-1) of propofol. The number of apoptotic cells in the head of propofol-treated 36 h postfertilization embryos were significantly increased, and the expression of caspases-3, -8 and -9 were upregulated. Apoptosis was also induced in the brain of 3 dpf larvae exposed to propofol. However, propofol caused a decrease in mbp gene and protein (dose-dependent) expression levels in the central nervous system of 3 dpf zebrafish. These data show that embryonic exposure to propofol is neurotoxic, causing increased apoptosis and decreased MBP expression. We believe zebrafish can be used as a novel model to explore the mechanisms of propofol neurotoxicity.

Guo|Peipei|P| Huang|Zhibin|Z| Tao|Tao|T| Chen|Xiaohui|X| Zhang|Wenqing|W| Zhang|Yiyue|Y| Lin|Chunshui|C|

Zebrafish
Developmental neurotoxicity
Propofol
Myelin basic protein
Cell apoptosis


Matrices for Sensors from Inorganic, Organic, and Biological Nanocomposites.

Abstract: Matrices and sensors resulting from inorganic, organic and biological nanocomposites are presented in this overview. The term nanocomposite designates a solid combination of a matrix and of nanodimensional phases differing in properties from the matrix due to dissimilarities in structure and chemistry. The nanoocomposites chosen for a wide variety of health and environment sensors consist of Anodic Porous Allumina and P450scc, Carbon nanotubes and Conductive Polymers, Langmuir Blodgett Films of Lipases, Laccases, Cytochromes and Rhodopsins, Three-dimensional Nanoporous Materials and Nucleic Acid Programmable Protein Arrays.

Nicolini|Claudio|C| Sivozhelezov|Victor|V| Bavastrello|Valter|V| Bezzerra|Tercio|T| Scudieri|Dora|D| Spera|Rosanna|R| Pechkova|Eugenia|E|


Costs and outcome of assertive community treatment (ACT) in a rural area in Denmark: 4-year register-based follow-up.

Abstract:
PURPOSE
Health economic evidence of assertive community treatment (ACT) in Denmark is limited. The aim of the study was to assess the costs and outcome of ACT among 174 patients with severe and persistent mental illness in a rural area of Denmark.

METHODS
The study was based on a quasi-experimental design with a control group from the neighbouring region. Costs and retention in mental health services were analysed by using register data 1 year before and 4 years after inclusion in the study. Data on the use of supportive housing were available for the year before baseline and the subsequent 2 years only.

RESULTS
Seventy eight percent of the patients receiving ACT were in contact with psychiatric services at the 4-year follow-up, while 69% of the patients in the control group had contact with psychiatric services (P < 0.17). Days in supportive housing were lower for the ACT group before baseline and remained so (dropping to zero) for the subsequent 2 years. Over 4 years, the mean total costs per patient in the group receiving ACT were DDK 493,442 (SE = 34,292). Excluding costs of supportive housing, the mean total costs per patient of the control group were DDK 537,218 (SE = 59,371), P < 0.53. If these costs are included, however, the mean total costs for the ACT group are unchanged, whereas costs for the control group rise to DDK 671,500 (SE = 73,671), P < 0.03.

CONCLUSION
While ACT appears to have resulted in a significant reduction in costs for psychiatric hospitalizations, baseline differences in use of supportive housing make the effects of ACT on overall costs more ambiguous. At worst, however, overall costs did not increase. Given the generally acknowledged clinical benefits of ACT over standard outpatient care, the results support further dissemination of ACT in Denmark.

D003156:Community Mental Health Services

D010043:Outcome and Process Assessment, Health Care

Costs
Assertive community treatment
Economic evaluation
Severe mental illness


On the Evolution of a Radical Concept: Affordances According to Gibson and Their Subsequent Use and Development.

Abstract: James J. Gibson, the founder of ecological psychology, introduced a radical empiricist approach to perception and action centered on direct perception in naturalistic environments that was counter to popular representational views of his time. This direct perception approach and the associated introduction of the affordance concept have been extremely influential in several fields of study. However, since its inception, the affordance concept has evolved in a manner such that it now deviates significantly from Gibson's original intention. This review follows use of the affordance concept by four sets of influential experimental psychologists: Gibson, Donald Norman, Mike Tucker and Rob Ellis, and Daniel Bub and Michael Masson. Particular attention is paid to the manner in which they applied the concept and the contributions provided by each set of researchers. The primary goal of this review is to determine what cognitive psychologists can take away from developments within the field and what considerations should be taken into account when using the term affordance. Having a more thorough understanding of the factors that led to the concept of affordance and its recent reformulations will better equip cognitive psychologists and, by extension, human factors researchers to further advance the study of perception-action relations.

affordances
ecological psychology
cognitive psychology
mental representation


Myocardial Fatty Foci in Tuberous Sclerosis Complex: Imaging Findings.

Abstract: Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic syndrome. The hallmark of the disease is multiple hamartomatous lesions in multiple organ systems. Common cardiac manifestations of TSC are rhabdomyomas, which are a benign tumor of striated muscle. In some patients with TSC, myocardial fatty foci (MFF) deposition has been described with or without the presence of rhabdomyomas. We present the case of a 24-year-old female with TSC and refractory seizures, who was evaluated with cardiac magnetic resonance (CMR) for an intracardiac right ventricular mass thought to be rhabdomyoma on echocardiography and for multiple areas of myocardial fatty deposition. Myocardial fatty deposition is a common finding in patients at cardiac imaging. In patients with TSC, it is critical that fatty deposits and lipomas are clearly distinguished from rhabdomyoma. CMR is an integral part of characterizing cardiac masses as it has superior soft tissue characterization and a wider field of view compared to echocardiography. A positive correlation has been shown between the number of MFF and the degree of extracardiac tuberous sclerosis (TS) manifestations suggesting that MFF may indicate more severe multiorgan disease in patients with TSC. Cardiac MR is superior to echocardiogram in evaluating and distinguishing intracardiac lipomas and fatty deposits from rhabdomyomas. Published studies have indicated that in patients with TSC, the presence of MFF correlates with the severity of multiorgan disease as was seen in our case.

Burt|Jeremy|J| Rop|Baiywo|B| Derrick|Edward|E| Armaly|Jamil|J| Siddiqui|Usman|U|

myocardial fatty foci
tuberous sclerosis complex
rhabdomyoma
cardiac imaging
cardiac lipoma
cardiac mri