Differences in the mitochondrial microsatellite instability of Keratoacanthoma and cutaneous squamous cell carcinoma.

Abstract: Keratoacanthoma (KA) is a common cutaneous neoplasm which often resembles typical squamous cell carcinoma (SCC) in both its clinical and historical presentation. Several studies have attempted to identify methods for distinguishing between KA and SCC, however, none of these have proven to play any obvious roles in these tumors. Given this we went on to evaluate mitochondrial microsatellite instability (mtMSI) in KA and SCC in an effort to understand these tumors better. DNA was isolated from paired normal and tumoral tissues donated by 57 KA patients and 43 SCC patients. MtMSI was then analyzed using eight microsatellite markers and was observed in 2 (3.5%) of the 57 KA patients and 8 (18.6%) of the 43 SCC patients, respectively. MtMSI was also shown to affect different locations depending on tumor type. In KA patients, mtMSI was detected at mitochondrial D514 D-loop and presented with (CA) n repeats, in contrast, all of the SCC patient experienced mtMSI at the D310 with (C)n repeats of the D-loop region. These differences in location were found to be significant, which may support the hypothesis that KA and SCC have different pathogenetic pathways. Our results also suggest that mtMSI may be a candidate for developing novel differential diagnostic methods for KA and SCC.

Alam|Mohammad Rizwan|MR|
Alsulimani|Ahmad|A|
Haque|Shafiul|S|
Jung|Hye Ra|HR|
Lee|Jae-Ho|JH|
Jeon|Chang-Ho|CH|
Kim|Dae-Kwang|DK|

D001483:Base Sequence
D002294:Carcinoma, Squamous Cell
D004272:DNA, Mitochondrial
D005819:Genetic Markers
D006801:Humans
D007636:Keratoacanthoma
D053842:Microsatellite Instability
D008928:Mitochondria
D012878:Skin Neoplasms


Attitudes: Mediators of the Relation between Health and Driving in Older Adults.

Abstract: We examined the relations between perceived health (e.g., self-perceived health status) and driving self-regulatory practices (e.g., frequency of driving, avoiding challenging driving situations) as mediated by driving attitudes and perceptions (i.e., driving comfort, positive and negative attitudes towards driving) in data collected for 928 drivers aged 70 and older enrolled in the Candrive II study. We observed that specific attitudes towards driving (e.g., driving comfort, negative attitudes towards driving) mediate the relations between health symptoms and self-regulatory driving behaviours at baseline and over time. Only negative attitudes towards driving fully mediated the relationships between changes in perceived health symptoms and changes in driving behavior. Perceived health symptoms apparently influence the likelihood of avoiding challenging driving situations through both initial negative attitudes towards driving as well as changes in negative attitudes over time. Understanding influences on self-regulatory driving behaviours will be of benefit when designing interventions to enhance the safety of older drivers.

Tuokko|Holly|H| Sukhawathanakul|Paweena|P| Walzak|Laura|L| Jouk|Alexandra|A| Myers|Anita|A| Marshall|Shawn|S| Naglie|Gary|G| Rapoport|Mark|M| Vrkljan|Brenda|B| Porter|Michelle|M|0000-0002-6333-6404 Man-Son-Hing|Malcolm|M| Mazer|Barbara|B| Korner-Bitensky|Nicol|N| Gélinas|Isabelle|I| Bédard|Michel|M| |||

attitudes
aging
older drivers
analyse de la médiation
auto-réglementation
changement comportemental
conducteurs âgés
longitudinal
mediation analysis
self-regulation
vieillissment


Nitrite Reduction in Aqueous Solution Mediated by Amavadin Homologues: N2 O Formation and Water Oxidation.

Abstract: Reactions of two vanadium(IV) complex anions that are homologues of amavadin, [V(HIDPA)2 ]2- and [V(HIDA)2 ]2- (HIDPA=N-oxyiminodipropionate, HIDA=N-oxyiminodiacetate), with the nitrite ion (NO2- ) in aqueous solution were investigated by experimental (absorption spectroscopy in the visible range, through measurements of dioxygen formed in solution from water oxidation and identification of nitrogen oxide species of a gaseous atmosphere from nitrite reduction by using an IR analyser) and theoretical methods. Two reactions, mediated by the vanadium complexes, with environmental and biological significance, were observed in this system, namely, reduction of nitrite to N2 O and oxidation of water to molecular oxygen. The reduction of nitrite, as studied by DFT calculations, occurs through the formation of NO (ΔG≠ =14.3 kcal mol-1 ), which is strongly dependent on pH and slightly endergonic, and is then easily converted into N2 O, with an overall activation barrier of ΔG≠ =11.8 kcal mol-1 . The later process includes dimerisation of NO assisted by one molecule of the V complex, protonation and oxidation of the formed ONNO.- ligand by another amavadin molecule or by nitrite, and NO bond cleavage/proton transfer in the ONNOH- ligand. The results indicate that amavadin exhibits an unusual nitrite reductase type activity that could be involved in nitrogen metabolism of Amanita muscaria and other fungi containing this vanadium complex.

da Silva|José Armando L|JAL|http://orcid.org/0000-0001-9708-1043

oxidation
vanadium
density functional calculations
natural products
reaction mechanisms


Tetrahydroacridine derivatives with dichloronicotinic acid moiety as attractive, multipotent agents for Alzheimer's disease treatment.

Abstract: A novel series of 9-amino-1,2,3,4-tetrahydroacridine and 5,6-dichloronicotinic acid moiety were conjugated with different linkers. Afterwards new derivatives were evaluated as potential multifunctional acetylcholinesterase inhibitors (AChEIs), anti-Alzheimer's disease (AD) drug candidates. All the compounds were synthesized and tested for capacity for the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes. Specifically, the most promising derivative 3b (IC50 = 1.02 nM) had higher inhibitory potency compared to the reference drug, tacrine. Consequently, kinetic studies of 3b compound showed a mixed-type inhibition of both AChE and BuChE. Afterwards the best potent AChE inhibitor has been examined on amyloid β (Aβ) self-induced aggregation. Furthermore, 3b compound was tested in various concentrations and had moderate activity against Aβ aggregation. Inhibition of Aβ aggregation was 46.63% and 19.41% at 50 μM and 5  μM concentrations, respectively. Moreover, no cytotoxicity was observed for the mentioned concentrations. Therefore, 3b compound is a promising multipotent agent for the treatment of AD.

Czarnecka|Kamila|K| Chufarova|Nina|N| Halczuk|Krzysztof|K| Maciejewska|Karolina|K| Girek|Małgorzata|M| Skibiński|Robert|R| Jończyk|Jakub|J| Bajda|Marek|M| Kabziński|Jacek|J| Majsterek|Ireneusz|I| Szymański|Paweł|P|

Multipotent agent
Alzheimer's disease
Acetylcholinesterase inhibitors
Molecular modeling
Multifunctional drugs


Emergency Laparoscopic Management of Perforative Peritonitis: A Retrospective Study.

Abstract: Background Peritonitis was previously considered a contraindication for minimally invasive surgery due to the risk of malignant hypercapnia partial pressure of carbon-dioxide (PCO2) and toxic shock syndrome. The objective of this retrospective study was to evaluate the role of laparoscopic surgery (LS) in selected patients with perforative peritonitis and to study its feasibility, safety, and outcomes. Patients and methods This was a retrospective study of 25 patients spanning over five years from 2015 to 2020. This study comprised all patients who were diagnosed with perforative peritonitis on preoperative physical/clinical examination, radiological evaluations, and who were stable enough to withstand pneumoperitoneum. Patients were evaluated for causes, operative time, duration of hospital stay, intra-, and postoperative complications, time taken to resume normal activity, and conversion to open surgery. Data was extracted from the hospital electronic medical records, for the above-mentioned parameters. Results Twenty-five patients with perforative peritonitis underwent diagnostic and therapeutic LS in our institute. The mean age was 46 years (35-79 years). Ten patients (40%) were diagnosed with gastro-duodenal perforation. Out of these ten patients, ninepatients (90%) were managed totally laparoscopically, while one patient (10%) required conversion to open surgery. There were 15 patients (60%) with small bowel perforation. Thirteen of the 15 patients were managed laparoscopically, with the remaining two requiring conversion to open surgery. The average time taken for the procedure was 90 minutes. The mean time to initiate the postoperative peroral liquid diet was 3.4 days. The mean postoperative stay was 6.9 days. The time taken to resume normal activity was 10-12 days. Conclusions Laparoscopic management is feasible and safe for patients with perforative peritonitis. Careful patient selection and the surgeon's experience with the procedure are critical determinants of success.

Harvitkar|Rafique Umer|RU|
Gattupalli|Giri Babu|GB|
Najmu|Sakib|S|
Joshi|Abhijit|A|

peritonitis
malignant hypercapnia
toxic shock syndrome
pneumoperitoneum
laparoscopy


Levetiracetam effectiveness as add-on therapy in Bulgarian patients with drug-resistant epilepsy.

Abstract:
INTRODUCTION
There are no reliable prospective studies on the effectiveness of LEV in Bulgarian adult patients with drug-resistant epilepsy.

AIM
The study aimed at conducting an open, prospective study on various aspects of levetiracetam (LEV) effectiveness in Bulgarian patients with drug-resistant epilepsy.

MATERIALS AND METHODS
The study was performed with patients with epilepsy recruited from those attending the Department of Neurology at the University Hospital in Plovdiv, Bulgaria. The patients completed diaries about seizure frequency, severity, and adverse events. There were regular documented visits at 3 or 6 months during the first year of treatment with LEV and at 6 months afterwards, with dynamic assessment of seizure frequency, severity, adverse events, and EEG recordings.

RESULTS
LEV was applied as an add-on therapy in 135 patients (86 males, mean age 35 years). There was a relatively mild and persisting dynamic improvement of seizure severity, a satisfactory seizure frequency reduction in 49.6% of participants, a persisting mean seizure frequency reduction (48-58%) from 6 to 36 months of treatment and a high responder rate (53-60%) during the same period. New seizure types (focal with impaired awareness with /without evolution to bilateral tonic-clonic seizures) occurred in 4 patients. There were adverse events (dizziness, memory impairment, aggressiveness, numbness, non-epileptic seizures, depression, anxiety, speech disturbances, visual hallucinations, sleepiness, pelvic muscles weakness, confusion, sleep disturbances, loss of appetite, unstable gait, hair loss, acne, generalized rash) in 13.33% of patients.

CONCLUSIONS
LEV treatment is associated with: low and persisting improvement of seizure severity, a good and persisting improvement of seizure frequency, a possible worsening of seizure control, a possible appearance of new seizure types, a good safety and tolerability.

Viteva|Ekaterina I|EI|
Zahariev|Zahari I|ZI|

levetiracetam
epilepsy
adverse events
tolerability
efficacy


Using plant chemistry and insect preference to study the potential of Barbarea (Brassicaceae) as a dead-end trap crop for diamondback moth (Lepidoptera: Plutellidae).

Abstract: Barbarea vulgaris R. Br. has been proposed as a dead-end trap crop for diamondback moth, Plutella xylostella L. (Lepidoptera: Plutellidae), because its larvae do not survive on this plant species despite being highly preferred for oviposition. We compared plants of several species, varieties, and types in the genus Barbarea (Brassicaceae) to study their potential as trap crops for P. xylostella. In terms of insect behavior, Barbarea plants were assessed based on the criteria of high oviposition preference by P. xylostella moths (compared to other Barbarea plants and to three Brassica oleracea L. crop varieties) and low survival of P. xylostella larvae. Barbarea plants were also assessed based on the criteria of high content of glucosinolates, which stimulate adult oviposition and larval feeding in P. xylostella, and high content of saponins, which are detrimental to survival of P. xylostella larvae. All Barbarea plants tested were preferred over cabbage by ovipositing P. xylostella. Among Barbarea plants, few significant differences in oviposition preference by P. xylostella were found. Ovipositing P. xylostella preferred B. vulgaris plants containing mainly 2-phenylethylglucosinolate over B. vulgaris plants containing mainly (S)-2-hydroxy-2-phenylethylglucosinolate, and P-type B. vulgaris var. arcuata plants over Barbarea rupicola and B. vulgaris var. variegata plants. Despite containing a lower content of saponins than other Barbarea plants tested, Barbarea verna did not allow survival of P. xylostella larvae. Our studies show that, except for B. rupicola and P-type B. vulgaris var. arcuata, which allowed survival of P. xylostella larvae, all Barbarea plants tested have potential as dead-end trap crops for P. xylostella.

Badenes-Perez|Francisco R|FR|
Reichelt|Michael|M|
Gershenzon|Jonathan|J|
Heckel|David G|DG|

Brassicaceae
Trap crop
Plutella xylostella
Oviposition preference
Glucosinolates
Saponins
Barbarea spp.
Feeding deterrent
Host plant resistance


Rice starch thin films as a potential buccal delivery system: Effect of plasticiser and drug loading on drug release profile.

Abstract: Rice starch is known to have an excellent film-forming behaviour in the packaging industry but inadequate attention was given to this biopolymer to be developed into thin films for drug delivery. Accordingly, rice starch thin films containing a model drug, paracetamol and plasticisers (glycerol or sorbitol) were developed using film casting technique. This study focuses on investigating the impact of plasticiser and drug loading on drug release pattern of rice starch films which has not been explored to date. The obtained rice films were characterised for their physicochemical properties including swelling and dissolution study. The highest drug dissolution rate was achieved in the rice films with a low drug loading due to drug amorphicity in nature. When drug loading increases, the swelling behaviour of rice films plays a dominant role in releasing drug in the crystalline form. The role of plasticiser was indicated by the plasticiser-starch interaction where a strong interaction allows drug solubilisation more readily in the dissolution medium. It is envisaged that rice films could be tailored to achieve desired drug release pattern with different plasticiser.

Chan|Siok Yee|SY|
Goh|Choon Fu|CF|
Lau|Jui Yeh|JY|
Tiew|Yi Cin|YC|
Balakrishnan|Thesigan|T|

Rice starch
Thin film
Plasticiser
Drug release
Paracetamol
Swelling


Apoptin as a Tumor-Specific Therapeutic Agent: Current Perspective on Mechanism of Action and Delivery Systems.

Abstract: Cancer remains one of the leading causes of death worldwide in humans and animals. Conventional treatment regimens often fail to produce the desired outcome due to disturbances in cell physiology that arise during the process of transformation. Additionally, development of treatment regimens with no or minimum side-effects is one of the thrust areas of modern cancer research. Oncolytic viral gene therapy employs certain viral genes which on ectopic expression find and selectively destroy malignant cells, thereby achieving tumor cell death without harming the normal cells in the neighborhood. Apoptin, encoded by Chicken Infectious Anemia Virus' VP3 gene, is a proline-rich protein capable of inducing apoptosis in cancer cells in a selective manner. In normal cells, the filamentous Apoptin becomes aggregated toward the cell margins, but is eventually degraded by proteasomes without harming the cells. In malignant cells, after activation by phosphorylation by a cancer cell-specific kinase whose identity is disputed, Apoptin accumulates in the nucleus, undergoes aggregation to form multimers, and prevents the dividing cancer cells from repairing their DNA lesions, thereby forcing them to undergo apoptosis. In this review, we discuss the present knowledge about the structure of Apoptin protein, elaborate on its mechanism of action, and summarize various strategies that have been used to deliver it as an anticancer drug in various cancer models.

Malla|Waseem Akram|WA|
Arora|Richa|R|
Khan|Raja Ishaq Nabi|RIN|
Mahajan|Sonalika|S|
Tiwari|Ashok Kumar|AK|

apoptin
oncolytic viral genes
chicken infectious anemia
VP3
CAV
anticancer genes
cancer gene therapy
oncotherapy


An Overview of Analytical Methods for the Determination of Monoamine Oxidase Inhibitors in Pharmaceutical Formulations and Biological Fluids.

Abstract: Monoamine oxidase inhibitors (MAOIs) were the first type of antidepressant developed. MAOIs elevate the levels of norepinephrine, serotonin, and dopamine by inhibiting an enzyme called monoamine oxidase. They are also used in the treatment of Parkinson's disease, tuberculosis, and several other disorders. Therefore, it is very important to develop efficient analytical methods for monitoring and management. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. In this article, analyses of MAOIs in pharmaceutical formulations and biological fluids were reviewed from 2000 to the present, including all types of chromatographic, spectrophotometric, electrophoretic, and voltammetric techniques, focusing on isoniazid, tranylcypromine, moclobemide, rasagiline, and selegiline.

Analytical methods
monoamine oxidase inhibitors
pharmaceutical formulations
biological fluids


The Role of Cultural and Family Values on Social Connectedness and Loneliness among Ethnic Minority Elders.

Abstract:
OBJECTIVES
Ethnic minority elders have high levels of social isolation and loneliness. Assumptions about the family providing enough social support exist in the literature, contradicting ethnic minority elders' reported levels of isolation and loneliness. While structural barriers influence feelings of isolation and loneliness, limited information exists about the role of cultural factors such as acculturation and family values. Accordingly, this study investigated the roles of acculturation and family values on loneliness and social isolation among ethnic minority elders.

METHODS
Ethnic minority elders (N = 123) completed a questionnaire that assessed their social connectedness, measured by social network and levels of loneliness, and structural factors such as income. Additionally, cultural and family values were assessed by acculturation and the 'family as referents' dimension of familism, which refers to the belief that family members' behaviour should meet with familial expectations.

RESULTS
Statistical analysis using hierarchical regression indicated that 'family as referents' and acculturation predicted loneliness, but not social network.

CONCLUSIONS
This study raises the importance of considering cultural values when investigating predictors of loneliness among ethnic minority elders.

CLINICAL IMPLICATIONS
Findings highlight the importance of addressing familial expectations in programs aimed at alleviating loneliness among ethnic minority elders.

Garcia Diaz|Laura|L|
Savundranayagam|Marie Y|MY|
Kloseck|Marita|M|
Fitzsimmons|Deborah|D|

family values
loneliness
ethnic minority elders
social isolation
familism
Cultural values


Periodicity in Structure, Bonding, and Reactivity for p-Block Complexes of a Geometry Constraining Triamide Ligand.

Abstract: The use of pincer ligands to access non-VSEPR geometries at main-group centers is an emerging strategy for eliciting new stoichiometric and catalytic reactivity. As part of this effort, several different tridentate trianionic substituents have to date been employed at a range of different central elements, providing a patchwork dataset that precludes rigorous structure-function correlation. An analysis of periodic trends in structure (solid, solution, and computation), bonding, and reactivity based on systematic variation of the central element (P, As, Sb, or Bi) with retention of a single tridentate triamide substituent is reported herein. In this homologous series, the central element can adopt either a bent or planar geometry. The tendency to adopt planar geometries increases descending the group with the phosphorus triamide (1) and its arsenic congener (2) exhibiting bent conformations, and the antimony (3) and bismuth (4) analogues exhibiting a predominantly planar structure in solution. This trend has been rationalized using an energy decomposition analysis. A rare phase-dependent dynamic covalent dimerization was observed for 3 and the associated thermodynamic parameters were established quantitatively. Planar geometries were found to engender lower LUMO energies and smaller band gaps than bent ones, resulting in different reactivity patterns. These results provide a benchmark dataset to guide further research in this rapidly emerging area.

pincer ligands
amides
main group elements
self-assembly


Applications of Ma'aljobon, a natural remedy from traditional Persian medicine, in dermatology: A journey from past to modernity.

Abstract: Ma'aljobon, a handmade substance, is the liquid portion of coagulated milk after adding vinegar to the heated milk. In traditional Persian medicine (TPM) it has been known as a useful remedy for the treatment of some skin disorders. The aim of this study was to review the applications of Ma'aljobon for skin diseases according to the sages of TPM and modern medicine. Main TPM sources were reviewed with the keyword of "Ma'aljobon." Furthermore, electronic databases including Scopus, PubMed, SID, and Google Scholar were searched with the keyword "Whey protein" during 2000 to 2018. According to TPM sources, Ma'aljobon was used by Iranian sages as a safe and effective remedy to treat a wide range of skin diseases, such as pimples, and ulcers. Meantime, recent evidence has also shown the effectiveness of whey protein in treating some skin disorders such as atopic dermatitis. Gastrointestinal discomfort was the most adverse effect of Ma'aljobon mentioned in TPM sources. In conclusion, there were several applications for Ma'aljobon in treatment of dermatologic disease according to TPM, as well as modern medicine. These finding could be the basis of future clinical trials on the effects of Ma'aljobon in the treatment of skin problems.

Ma'aljobon
Persian medicine
review
skin diseases
whey protein
traditional medicine


Late onset Warfarin induced skin necrosis in human immunodeficiency virus infected patient with pulmonary tuberculosis.

Abstract: The incidence of Warfarin-induced skin necrosis (WISN) is very low 0.01-0.10%. The majority of the WISN cases appear between day 3 and 6 of onset of Warfarin therapy. The cases of late onset WISN are rarely seen. We report a case of late onset WISN in a young human immunodeficiency virus positive female patient with thrombotic pulmonary embolism and reactivation of pulmonary tuberculosis.

Choudhary|Sanjiv Vijay|SV|
Madnani|Amrita|A|
Singh|A L|AL|

late onset
Warfarin
skin necrosis
Human immunodeficiency virus


Transcripts of pectin-degrading enzymes and isolation of complete cDNA sequence of a pectate lyase gene induced by coffee white stem borer (Xylotrechus quadripes) in the bark tissue of Coffea canephora (robusta coffee).

Abstract: Of the two commercially cultivated coffee (Coffea) species, C. arabica (arabica) is highly susceptible and C. canephora (robusta) is highly resistant to the insect pest Xylotrechus quadripes (Coleoptera: Cerambycidae), commonly known as coffee white stem borer (CWSB). We constructed a forward-subtracted cDNA library by Suppression Subtractive Hybridization (SSH) from robusta bark tissue for profiling genes induced by CWSB infestation. Among the 265 unigenes of the SSH EST library, 7 unigenes (5 contigs and 2 singletons) matching different pectin-degrading enzymes were discovered. These ESTs matched one pectate lyase, three polygalacturonases, and one pectin acetylesterase gene. Quantitative real-time PCR (qRT-PCR) revealed that CWSB infestation strongly induces the pectate lyase gene at 72 h. Complete cDNA sequence of the pectate lyase gene was obtained through 3' and 5' RACE reactions. It was a 1595 bp long sequence that included full CDS and both UTRs. Against C. canephora genome sequences in Coffee Genome Hub database ( http://coffee-genome.org/ ), it had 22 matches to different pectate lyase genes mapped on 9 of the 11 pseudochromosomes, the top match being Cc07_g00190 Pectate lyase. In NCBI database, it matched pectate lyase sequences of several plants. Apart from C. canephora, the closest pectate lyase matches were from Sesamum indicum and Nicotiana tabacum. The pectinolytic enzymes discovered here are thought to play a role in the production of oligogalacturonides (OGs) which act as Damage-Associated Molecular Pattern (DAMP) signals eliciting innate immunity in plants. The pectate lyase gene, induced by CWSB infestation, along with other endogenous pectinolytic enzymes and CWSB-specific elicitors, may be involved in triggering basal defense responses to protect the CWSB-damaged tissue against pathogens, as well as to contain CWSB in robusta.

Bharathi|Kosaraju|K|
Santosh|P|P|
Sreenath|H L|HL|

Suppression subtractive hybridization (SSH)


The Violent Behavior Vignette Questionnaire (VBVQ): A Measure of Violent Behavior for Research in Forensic and Non-Forensic Settings and Populations.

Abstract: The measurement of violent behavior presents serious challenges for research on violence. In the current article, we present initial tests of the construct validity of scores on the Violent Behavior Vignette Questionnaire (VBVQ), which consists of a series of interpersonal conflict vignettes with response options in a multiple-choice format designed to measure current violent behavior. Violent responses on the initial version of the VBVQ generally corresponded to independent indicators of physical aggressiveness and violent behavior among male university students, men in the community, and incarcerated male offenders. We then refined the VBVQ and again tested the validity of its scores in new samples of men in the community and incarcerated male offenders. In both samples, men who selected a violent response option on the VBVQ generally had much higher levels of physical aggressiveness and violent behavior than did men who selected non-violent response options. However, VBVQ responses were not associated with the number of violent offenses in offenders' official criminal records. Our findings provide some support for the use of the VBVQ in lab and correctional/forensic research, but further research is required to determine whether it offers advantages over other measures.

vignettes
Violence
construct validity
offenders
analog


Honey bee (Apis mellifera) sociability and nestmate affiliation are dependent on the social environment experienced post-eclosion.

Abstract: Underpinning the formation of a social group is the motivation of individuals to aggregate and interact with conspecifics, termed sociability. Here, we developed an assay, inspired by vertebrate approaches to evaluate social behaviours, to simultaneously examine the development of honey bee (Apis mellifera) sociability and nestmate affiliation. Focal bees were placed in a testing chamber which was separated from groups of nestmates and conspecific non-nestmates by single-layer mesh screens. Assessing how much time bees spent contacting the two mesh screens allowed us to quantify simultaneously how much bees sought proximity and interaction with other bees and their preference for nestmates over non-nestmates. Both sociability and nestmate affiliation could be detected soon after emergence as an adult. Isolation early in adult life impaired honey bee sociability but there was no evidence for a critical period for the development of the trait, as isolated bees exposed to their hive for 24 h when as old as 6 days still recovered high levels of sociability. Our data show that, even for advanced social insects, sociability is a developmental phenomenon and experience dependent.

Hewlett|Susie E|SE|
Wareham|Deborah M|DM|
Barron|Andrew B|AB|0000-0002-8135-6628

Aggregation
Isolation
Social insect
Group cohesion
Nestmate recognition


Validation of the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia or Mild Cognitive Impairment (ETAM).

Abstract:
BACKGROUND
There are currently no valid, fast, and easy-to-administer performance tests that are designed to assess the capacities to perform activities of daily living in persons with mild dementia and mild cognitive impairment (MCI). However, such measures are urgently needed for determining individual support needs as well as the efficacy of interventions. The aim of the present study was therefore to validate the Erlangen Test of Activities of Daily Living in Persons with Mild Dementia and Mild Cognitive Impairment (ETAM), a performance test that is based on the International Classification of Functioning and Health (ICF), which assesses the relevant domains of living in older adults with MCI and mild dementia who live independently.

METHODS
The 10 ICF-based items on the research version of the ETAM were tested in a final sample of 81 persons with MCI or mild dementia. The items were selected for the final version in accordance with 6 criteria: 1) all domains must be represented and have equal weight, 2) all items must load on the same factor, 3) item difficulties and item discriminatory powers, 4) convergent validity (Bayer Activities of Daily Living Scale [B-ADL]) and discriminant validity (Mini Mental State Examination [MMSE], Geriatric Depression Scale 15 [GDS-15]), 5) inter-rater reliabilities of the individual items, 6) as little material as possible. Retest reliability was also examined. Cohen's ds were calculated to determine the magnitudes of the differences in ETAM scores between participants diagnosed with different grades of severity of cognitive impairment.

RESULTS
The final version of the ETAM consists of 6 items that cover the five ICF domains communication, mobility, self-care, domestic life (assessed by two 3-point items), and major life areas (specifically, the economic life sub-category) and load on a single factor. The maximum achievable score is 30 points (6 points per domain). The average administration time was 35 min, 19 of which were needed for pure item performance. The internal consistency was α = .71. The three-week test-retest reliability was r = .78, and the inter-rater reliability was r = .97. The ETAM also provided satisfactory discrimination between healthy individuals and persons with MCI or mild dementia as well as between persons with mild and moderate dementia.

CONCLUSIONS
The 6-item final version of the ETAM shows satisfactory psychometric characteristics and can be administered quickly. It is therefore suitable for use in both clinical practice and research.

Luttenberger|Katharina|K| Reppermund|Simone|S| Schmiedeberg-Sohn|Anke|A| Book|Stephanie|S| Graessel|Elmar|E|

Validity
Activities of daily living
Dementia
Mild cognitive impairment
Performance test


Immunoblotting using Strongyloides venezuelensis larvae, parthenogenetic females or eggs extracts for the diagnosis of experimentally infected immunosuppressed rats.

Abstract: The nematode Strongyloides stercoralis is responsible for strongyloidiasis in humans. Diagnosis of infection occurs through detection of larvae in feces, but low elimination of larvae often hampers the detection of disease, particularly in cases of patient immunosuppression. Immunodiagnostic tests have been developed; however obtaining S. stercoralis larvae for the production of homologous antigen extract is technically difficult. Thus, the use different developmental forms of Strongyloides venezuelensis has become an alternative method for the production of antigen extracts. The aim of this study was to evaluate immunoblotting using alkaline extracts from S. venezuelensis L3 larvae, parthenogenetic females or eggs to test detection of experimental strongyloidiasis associated with immunosuppression. Immunocompetent and immunosuppressed male rats were experimentally infected, and serum sample from all animals were obtained at 0, 5, 8 13, and 21 days post infection (d.p.i.). Immunoblotting was evaluated for use in detection of anti-S. venezuelensis IgG in both experimental rat groups. The larval extract immunoblotting profile had the most immunoreactive fractions in the immunosuppressed group beginning at 5 d.p.i., while the immunocompetent group reactivity began on 8 d.p.i. Immunoreactive protein fractions of 17 kDa present in larval alkaline extract presented as possible markers of infection in immunosuppressed rats. It is concluded that all extracts using immunoblotting have diagnostic potential in experimental strongyloidiasis, particularly larval extract in immunosuppressed individuals.

Goulart de Carvalho|Edson Fernando|EF|
Neto de Sousa|José Eduardo|JE|
Gonçalves|Ana Lúcia Ribeiro|AL|
da Cunha-Junior|Jair Pereira|JP|
Costa-Cruz|Julia Maria|JM|

Immunoblotting
Strongyloides venezuelensis
Rats
Immunossupression


Colonic biogeography in health and ulcerative colitis.

Abstract: The relevance of biogeography to the distal gut microbiota has been investigated in both health and inflammatory bowel disease (IBD), however multiple factors, including sample type and methodology, microbiota characterization and interpersonal variability make the construction of a core model of colonic biogeography challenging. In addition, how phylogenetic classification relates to immunogenicity and whether consistent alterations in the microbiota are associated with ulcerative colitis (UC) remain open questions. This addendum seeks to review the human colonic microbiota in health and UC as currently understood, in the broader context of the human microbiome.

Lavelle|Aonghus|A|
Lennon|Grainne|G|
Winter|Desmond C|DC|
O'Connell|P Ronan|PR|

Biogeography
ulcerative colitis
microbiota
inflammatory bowel disease
microbiome
spatial ecology


Proteomic-based biomarker discovery for development of next generation diagnostics.

Abstract: In the post-genome age, proteomics is receiving significant attention because they provide an invaluable source of biological structures and functions at the protein level. The search for disease-specific biomarkers for diagnostic and/or therapeutic applications is one of the areas that proteomics is having a significant impact. Thus, the identification of a "good" biomarker enables a more accurate early diagnosis and prognosis of disease. Rapid advancements in mass spectrometry (MS) instrumentation, liquid chromatography MS (LCMS), protein microarray technology, and other protein profiling methodologies have a substantial expansion of our toolbox to identify disease-specific protein and peptide biomarkers. This review covers a selection of widely used proteomic technologies for biomarker discovery. In addition, we describe the most commonly used approaches for diagnosis based on proteomic biomarkers and further discuss trends and critical challenges during development of cost-effective rapid diagnostic tests and microfluidic diagnostic systems based on proteomic biomarkers.

Khalilpour|Akbar|A|
Kilic|Tugba|T|
Khalilpour|Saba|S|
Álvarez|Mario Moisés|MM|
Yazdi|Iman K|IK|

Biomarker discovery
Proteomic
Diagnostic kits
Microfluidic systems


Genome profiling of fluoroquinolone-resistant uropathogenic Escherichia coli isolates from Brazil.

Abstract: Urinary tract infections (UTIs) are a major public health concern in both community and hospital settings worldwide. Uropathogenic Escherichia coli (UPEC) is the main causative agent of UTI and increasingly associated with antibiotic resistance. Herein, we report the draft genome sequence of 9 fluoroquinolone-resistant UPEC isolates from Brazil and examine selected major phenotypic features, such as antimicrobial resistance profile, phylogroup, serotype, sequence type (ST), virulence genes, and resistance marks. Besides the quinolone resistance, beta-lactams, ESBL production, aminoglycosides, and tetracycline resistance were observed. High prevalence of 20 virulence genes was detected in all isolates, such as those encoding type 1 fimbriae, acid tolerance system, and hemolysin E, particularly within E. coli B2 phylogroup, as ST131 and ST1193 strains, among other genomic analyses as genomic islands, resistance plasmids, and integron identification.

da Silva|Patrick|P|
Lustri|Bruna C|BC|
Castilho|Ivana Giovannetti|IG|
Ferreira|Adriano Martison|AM|
Hernandes|Rodrigo T|RT|
Schembri|Mark A|MA|
Moreira|Cristiano G|CG|

Fluoroquinolone-resistant
Escherichia coli
UTI
UPEC
Pathogenesis


Evaluating screening colonoscopy quality in an uninsured urban population following patient navigation.

Abstract: Patient navigation (PN) increases screening colonoscopy completion in minority and uninsured populations. However, colonoscopy quality is under-reported in the setting of PN and quality indicators have often failed to meet benchmark standards. This study investigated screening colonoscopy quality indicators after year-one of a PN initiative targeting the medically uninsured. This was a retrospective analysis of 296 outpatient screening colonoscopies. Patients were 45 to 75 years of age with no history of bowel cancer, inflammatory bowel disease, or colorectal surgery. The screening colonoscopy quality indicators: adenoma detection rate (ADR), cecal intubation rate (CIR), and bowel preparation quality were compared in 89 uninsured Federally Qualified Health Center (FQHC) patients who received PN and 207 University Hospital patients who received usual care. The FQHC PN and University Hospital cohorts were similar in female sex (69% vs. 70%; p = 0.861) and African American race (61% vs. 61%; p = 0.920). The FQHC PN cohort was younger (57 years vs. 60 years; p < 0.001). There was no difference in ADR (33% vs. 32%; p = 0.971) or CIR (96% vs. 95%; p = 0.900) comparing the FQHC PN and University Hospital cohorts. The FQHC PN patients had a greater likelihood of an optimal bowel preparation on multivariate logistic regression (odds ratio 4.17; 95% confidence interval 1.07 to 16.20). Uninsured FQHC patients who received PN were observed to have intra-procedure quality indicators that exceeded bench-mark standards for high-quality screening colonoscopy and were equivalent to those observed in an insured University Hospital patient population.

Naylor|Keith|K| Fritz|Cassandra|C| Polite|Blase|B| Kim|Karen|K|

CRCSI, Colorectal Cancer Screening Initiative


Rapid detection and identification of bacteria directly from whole blood with light scattering spectroscopy based biosensor.

Abstract: Bacterial infections are one of the major causes of death worldwide. The identification of a bacterial species that is the source of an infection generally takes a long time, and often exceeds the treatment window for seriously ill patients. Many of these deaths are preventable if the bacterial species can be identified quickly. Here we present an optical spectroscopic method for rapid detection and identification of bacteria directly from whole blood using a light scattering spectroscopy technique. This technique was originally developed to detect pre-cancerous changes in epithelial tissues, characterize changes in tissue on the cellular scale, and characterize biological structures comparable to or smaller than a single wavelength. We demonstrate here that not only can an inexpensive light scattering spectroscopy-based biosensor rapidly detect and identify four bacteria species in the blood, responsible for the majority of death causing infections, but that species-level identification can potentially be made based on approximately one thousand bacterial cells per milliliter of blood. Observing entire colonies or performing susceptibility testing is therefore not required.

Qiu|Le|L|
Zhang|Lei|L|
Horowitz|Gary L|GL|
Turzhitsky|Vladimir|V|
Coughlan|Mark F|MF|
Glyavina|Maria|M|
Khan|Umar|U|
Zakharov|Yuri N|YN|
Vitkin|Edward|E|
Itzkan|Irving|I|
Perelman|Lev T|LT|

Rapid detection
Bacteria
Whole blood
Light scattering spectroscopy
Sepsis


Mechanically induced deformation and strain dynamics in actin stress fibers.

Abstract: It is becoming evident that physical forces in the microenvironment play a key role in regulating many important aspects of cell biology. However, although mechanical cues are known to have clear effects over the long-term (days), the short-term (seconds to minutes) cellular responses to mechanical stimuli are less well characterized. In our recent study, we exposed committed fibroblast cells to well controlled nanoscale forces while simultaneously imaging force transduction through the actin cytoskeleton. One of the earliest responses of a cell to physical force is rapid deformation of the cytoskeleton, taking place over the course of seconds. We were able to directly visualize deformation, force-propagation and strain dynamics in actin stress fibers in response to a relatively simple mechanical stimulus. Moreover, these dynamics were also dependent on myosin-driven contractility and the presence of an intact microtubule cytoskeleton. Interestingly, although stem cells are sensitive to mechanical cues, they do not display the same degree of stress fiber organization as observed in committed cells indicating the possibility of alternative sensing and mechanotransduction mechanisms.

Hadjiantoniou|Sebastian|S|
Guolla|Louise|L|
Pelling|Andrew E|AE|

strain actin cytoskeleton mechanotransduction nanomechanics


Inhibition of Staphylococcus aureus LC554891 by Moringa oleifera Seed Extract either Singly or in Combination with Antibiotics.

Abstract: Bacterial outbreaks caused by Staphylococcus aureus (S. aureus) are interesting due to the existence of multidrug resistant (MDR) isolates. Therefore, there is a need to develop novel ways to control such MDR S. aureus. In this study, some natural agents such as honey bee (HB), extracts of either Moringa oleifera seeds (MSE), or leaves (MLE) and essential oils of garlic, clove, and moringa were studied for their inhibitory activity against this S. aureus pathogen. About 100 food samples including beef luncheon (n = 25), potato chips (n = 50), and corn flakes (n = 25) were investigated for possible pollution with the S. aureus bacteria. The isolated bacteria suspected to belong S. aureus that grew well onto Baird-Parker agar (Oxoid) and shiny halo zones and positive coagulase reaction were selected and identified by API-Kits; all of them that were approved belong to S. aureus (18 strains). The sensitivity of the obtained 18 S. aureus bacterial strains to 12 antibiotics were evaluated; all of them were resistant to ofloxacin; however, other antibiotics tested showed variable results. Interestingly, the S. aureus No. B3 isolated from beef luncheon was resistant to10 antibiotics out of 12 ones tested. Multiple antibiotic resistance index (MAR) of this S. aureus strain was about 83.3%. Therefore, its identification was confirmed by sequencing of a 16S rRNA gene which approved a successful biochemical identification carried out by API Kits and such strain was designated S. aureus LC 554891. The genome of such strain appeared to contain mecA gene encoding methicillin resistance; it was found to contain hla, hlb, tsst-1, and finbA that encode α-blood hemolysis, β-blood hemolysis, toxic shock syndrome gene, and fibrinogen-binding protein gene, respectively. In addition, the virulence factors viz. sea; seb; sec encoding enterotoxins were detected in the DNA extracted from S. aureus B3 strain. Aqueous extract of Moringa oleifera seeds (MSE) showed inhibitory activity against S. aureus LC 554891 better than that obtained by tetracycline, essential oils or HB. Minimum inhibitory concentration (MIC) of MSE was 20µg/mL. Instrumental analysis of MSE showed 14 bioactive chemical compounds. Combinations of both MSE and tetracycline showed distinctive inhibitory activity against S. aureus LC 554891 than that obtained by either tetracycline or MSE singly.

D000900:Anti-Bacterial Agents
D008826:Microbial Sensitivity Tests
D029588:Moringa oleifera
D012336:RNA, Ribosomal, 16S
D013211:Staphylococcus aureus
D037521:Virulence Factors

Staphylococcus aureus
moringa
MSE
virulence factors
GC-MS analysis


Inhibitory mechanisms of celastrol on human liver cytochrome P450 1A2, 2C19, 2D6, 2E1 and 3A4.

Abstract: 1. The present study was conducted to examine the possibility of herb-drug interaction by celastrol, which is a main compound isolated from Tripterygium wilfordii Hook F. using human liver microsomes with cocktail methods. Focused on its inhibitory manner on the metabolism of model probe substrates of five cytochrome P450 isoenzymes (CYP1A2, CYP2C19, CYP2D6, CYP2E1 and CYP3A4) in vitro which are important with the metabolism of different xenobiotics. 2. The results showed that celastrol inhibited the five types of human cytochrome P450 isoforms, with the IC50 values of 2.65 μM (CYP3A4), 5.99 μM (CYP2C19), 6.27 μM (CYP2D6), 7.66 μM (CYP1A2) and 9.38 μM (CYP2E1), respectively. The data indicated that celastrol acted in different manners as an inhibitor of human cytochrome P450 isoforms, which showed that celastrol not only un-competitively inhibited the CYP1A2 and 2E1 activities, but also competitively inhibited the CYP2C19 and 2D6 activities with Ki values of 1.41, 2.29, 5.27 and 4.21 μM, respectively. Celastrol was also a mixed-type inhibitor of CYP3A4, with Ki and Kis values of 2.02 and 5.49 μM, respectively. 3. Celastrol has the potential to inhibit cytochrome P450 activities and may cause the herb-drug interactions. Therefore, the use of celastrol and its preparations with conventional medicines should thus be taken in to account.

Jin|Chunhuan|C| He|Xin|X| Zhang|Fangliang|F| He|Lina|L| Chen|Junxiu|J| Wang|Lili|L| An|Lijun|L| Fan|Yaowen|Y|

D065607:Cytochrome P-450 Enzyme Inhibitors

in vitro
inhibition
CYP
herb–drug interaction (HDI)


Comparative Transcriptomic Analysis of the Hematopoietic System between Human and Mouse by Single Cell RNA Sequencing.

Abstract: (1) Background: mouse models are fundamental to the study of hematopoiesis, but comparisons between mouse and human in single cells have been limited in depth. (2) Methods: we constructed a single-cell resolution transcriptomic atlas of hematopoietic stem and progenitor cells (HSPCs) of human and mouse, from a total of 32,805 single cells. We used Monocle to examine the trajectories of hematopoietic differentiation, and SCENIC to analyze gene networks underlying hematopoiesis. (3) Results: After alignment with Seurat 2, the cells of mouse and human could be separated by same cell type categories. Cells were grouped into 17 subpopulations; cluster-specific genes were species-conserved and shared functional themes. The clustering dendrogram indicated that cell types were highly conserved between human and mouse. A visualization of the Monocle results provided an intuitive representation of HSPC differentiation to three dominant branches (Erythroid/megakaryocytic, Myeloid, and Lymphoid), derived directly from the hematopoietic stem cell and the long-term hematopoietic stem cells in both human and mouse. Gene regulation was similarly conserved, reflected by comparable transcriptional factors and regulatory sequence motifs in subpopulations of cells. (4) Conclusions: our analysis has confirmed evolutionary conservation in the hematopoietic systems of mouse and human, extending to cell types, gene expression and regulatory elements.

Gao|Shouguo|S|
Wu|Zhijie|Z|
Kannan|Jeerthi|J|
Mathews|Liza|L|0000-0002-9977-7631
Feng|Xingmin|X|0000-0001-8018-2366
Kajigaya|Sachiko|S|
Young|Neal S|NS|

hematopoiesis
cross-species analysis
gene regulatory network
single-cell RNA sequencing


Association of bezafibrate with transplant-free survival in patients with primary biliary cholangitis.

Abstract:
BACKGROUND & AIMS
A beneficial effect of bezafibrate (BZF) on symptoms and biochemical features of primary biliary cholangitis (PBC) has been reported in patients with an incomplete response to ursodeoxycholic acid (UDCA), but long-term effects on survival remain unknown. In Japan, BZF has been used as a de facto second-line therapy for PBC since 2000. Herein, we compared the survival rates between patients treated with and those without BZF in a large nationwide Japanese PBC cohort.

METHODS
All consecutively registered patients of this cohort who started UDCA therapy from 2000 onwards and had a follow-up ≥1 year were included. Association between BZF exposure and mortality or need for liver transplantation (LT) was assessed using time-dependent, multivariable-and propensity score-adjusted Cox proportional hazards models. Clinical benefit was quantified using the number needed to treat (NNT).

RESULTS
Of 3,908 eligible patients, 3,162 (81%) received UDCA only and 746 (19%) UDCA and BZF over 17,360 and 3,932 patient-years, respectively. During follow-up, 183 deaths (89 liver-related) and 21 LT were registered. Exposure to combination therapy was associated with a significant decrease in all-cause and liver-related mortality or need for LT (adjusted hazard ratios: 0.3253, 95% CI 0.1936-0.5466 and 0.2748, 95% CI 0.1336-0.5655, respectively; p <0.001 for both). This association was consistent across various risk groups at baseline. The NNTs with combination therapy to prevent 1 additional death or LT over 5, 10, and 15 years were 29 (95% CI 22-46), 14 (10-22), and 8 (6-15), respectively.

CONCLUSIONS
In a large retrospective cohort study of treatment effects in patients with PBC, the addition of BZF to UDCA was associated with improved prognosis.

LAY SUMMARY
The long-term efficacy of bezafibrate (BZF) on liver transplantation (LT) - free survival in patients with PBC and an incomplete response to ursodeoxycholic acid (UDCA) remains to be determined. In this Japanese nationwide retrospective cohort study, the use of UDCA-BZF combination therapy, compared to UDCA alone, was associated with a lower risk of all-cause and liver-related mortality or need for LT. These results indicate that BZF is so far the only drug in PBC to have demonstrated efficacy in improving symptoms, biochemical markers, and long-term outcomes.

Tanaka|Atsushi|A|
Hirohara|Junko|J|
Nakano|Toshiaki|T|
Matsumoto|Kosuke|K|
Chazouillères|Olivier|O|
Takikawa|Hajime|H|
Hansen|Bettina E|BE|
Carrat|Fabrice|F|
Corpechot|Christophe|C|


Provider Experience and the Comparative Safety of Laparoscopic and Open Colectomy.

Abstract:
OBJECTIVE
To evaluate the comparative safety of laparoscopic and open colectomy across surgeons varying in experience with laparoscopy.

DATA SOURCES
National Medicare data (2008-2010) for beneficiaries undergoing laparoscopic or open colectomy.

STUDY DESIGN
Using instrumental variable methods to address selection bias, we evaluated outcomes of laparoscopic and open colectomy. Our instrument was the regional use of laparoscopy in the year prior to a patient's operation. We then evaluated outcomes stratified by surgeons' annual volume of laparoscopic colectomy.

PRINCIPAL FINDINGS
Laparoscopic colectomy was associated with lower mortality (OR: 0.75, 95 percent CI: 0.70-0.78) and fewer complications than open surgery (OR: 0.82, 95 percent CI: 0.79-0.85). Increasing surgeon volume was associated with better outcomes for both procedures, but the relationship was stronger for laparoscopy. The comparative safety depended on surgeon volume. High-volume surgeons had 40 percent lower mortality (OR: 0.60, 95 percent CI: 0.55-0.65) and 30 percent fewer complications (OR: 0.70, 95 percent CI: 0.67-0.74) with laparoscopy. Conversely, low-volume surgeons had 7 percent higher mortality (OR: 1.07, 95 percent CI: 1.02-1.13) and 18 percent more complications (OR: 1.18, 95 percent CI: 1.12-1.24) with laparoscopy.

CONCLUSIONS
This population-based study demonstrates that the comparative safety of laparoscopic and open colectomy is influenced by surgeon volume. Laparoscopic colectomy is only safer for patients whose surgeons have sufficient experience.

Sheetz|Kyle H|KH|
Norton|Edward C|EC|
Birkmeyer|John D|JD|
Dimick|Justin B|JB|

Comparative safety
colectomy
instrumental variables


The performance of the interferon gamma assay when used as a diagnostic or quality assurance test in Mycobacterium bovis infected herds.

Abstract: There are two different contexts in the Irish bTB eradication programme in which the interferon-gamma assay (IFN-γ) is applied. Firstly, the IFN-γ assay is applied routinely to high risk cohorts in herds with four or more reactors to the SICTT. The IFN-γ test is then carried out on blood samples submitted to the laboratory within 8h of collection (diagnostic testing). Secondly, the use of the IFN-γ assay has recently been extended to test SICTT reactors as part of a general quality assurance (QA) scheme to monitor the performance of the SICTT. Blood samples from reactors are tested one day after blood collection (QA testing). In this study, we analysed the relative performance of the SICTT and IFN-γ when used in parallel as an 8h diagnostic test and as a 24h QA test on SICTT reactors. A total of 17,725 IFN-γ tests were included in the analysis (11,658 diagnostic tests and 6067 QA tests). Of the samples submitted for diagnostic testing, the proportion positive to IFN-γ decreased with the severity of interpretation of the SICTT result. Of the standard reactors that were tested with IFN-γ in the QA programme, 92.2% were positive to the IFN-γ test. Among animals that were SICTT -ve/IFN-γ +ve, 18.9% were positive at post-mortem compared to 11.8% of those that were SICTT +ve (standard reactor)/IFN-γ -ve. These results highlight the risk associated with retaining SICTT -ve/IFN-γ +ve animals, and suggest that prompt removal of these animals is necessary to reduce the potential for future transmission.

Clegg|T A|TA|
Good|M|M|
Doyle|M|M|
Duignan|A|A|
More|S J|SJ|
Gormley|E|E|

Single intradermal comparative tuberculin test (SICTT)


Prognostic aspects of dynamic contrast-enhanced magnetic resonance imaging in synchronous distant metastatic rectal cancer.

Abstract:
OBJECTIVES
To explore the correlations between DCE-MRI quantitative parameters and synchronous distant metastasis and the clinicopathological factors in rectal cancers.

METHODS
Sixty-three patients with rectal cancer (synchronous distant metastasis, n = 31; non-metastasis, n = 32) were enrolled in this study. Student's t test and ANOVA were used to compare DCE-MRI parameters (K trans , K ep and V e ). The receiver operating characteristic (ROC) analysis was used to find the reasonable threshold of DCE-MRI parameters to differentiate lesions with synchronous distant metastasis from those without metastasis.

RESULTS
The K trans , K ep , and V e value were significantly higher in the lesions with distant metastasis than in the lesions without distant metastasis (0.536 ± 0.242 vs. 0.299 ± 0.118 min-1, p < 0.001; 1.598 ± 0.477 vs. 1.341 ± 0.390 min-1, p = 0.022; and 0.324 ± 0.173 vs. 0.249 ± 0.091, p = 0.034; respectively). The K trans showed the highest AUCs of 0.788 (p < 0.001), with sensitivity of 61.29 % and specificity of 87.5 %, respectively.

CONCLUSIONS
DCE-MRI parameters may represent a prognostic indicator for synchronous distant metastases in patients with rectal cancer.

KEY POINTS
• The K trans , K ep and V e values correlated with synchronous distant metastasis. • Higher K trans , K ep and V e values were noted among patients with metastasis. • DCE-MRI parameters might represent a prognostic indicator for synchronous distant metastases.

Yu|Jing|J| Xu|Qing|Q| Huang|Dong-Ya|DY| Song|Jia-Cheng|JC| Li|Yan|Y| Xu|Lu-Lu|LL| Shi|Hai-Bin|HB|

Rectal cancer
DCE-MRI
Quantitative parameters
Synchronous distant metastasis
Clinicopathological factors


Intraoperative seizure outcome of levetiracetam combined with perampanel therapy in patients with glioma undergoing awake brain surgery.

Abstract:
OBJECTIVE
This study aimed to evaluate the efficacy of levetiracetam (LEV) combined with perampanel (PER) therapy for intraoperative seizure treatment to determine whether a combination of LEV and PER can aid in the prevention of intraoperative intractable seizures during awake surgery.

METHODS
The authors performed a retrospective cohort study in 78 consecutive patients with glioma who underwent awake surgery using intraoperative direct electrical stimulation mapping. To prevent intraoperative seizures, 50 patients were treated with the antiepileptic drug LEV only (LEV group) from January 2017 to January 2019, while the remaining 28 patients were treated with LEV plus PER (LEV + PER group) between March 2019 and January 2020. LEV (1000-3000 mg) and/or PER (2-4 mg) were administered before the surgery.

RESULTS
Preoperative seizures with International League Against Epilepsy (ILAE) class II-VI occurred in 44% of the patients in the LEV group and in 35.7% of patients in the LEV + PER group, with no significant difference between groups (p = 0.319). Total intraoperative seizures occurred in 18 patients (36.0%) in the LEV therapy group and in 2 patients (7.1%) in the LEV + PER group (p = 0.009). Of these, there were no patients (0%) with intractable seizures in the LEV + PER group. Regarding factors that influence intraoperative seizures in glioma patients during awake brain surgery, multivariate logistic regression models revealed that the occurrence of intraoperative seizures was significantly related to the involvement of motor-related regions (positive vs negative, HR 6.98, 95% CI 1.71-28.56, p = 0.007), preoperative seizure (ILAE class II-VI vs ILAE class I, HR 4.44, 95% CI 1.22-16.11, p = 0.024), and LEV + PER group (positive vs negative, HR 0.07, 95% CI 0.01-0.44, p = 0.005). Treatment-related adverse effects were rare and mild, including sleepiness, tiredness, and dizziness in both treatment groups.

CONCLUSIONS
This study demonstrates that LEV + PER therapy is significantly associated with a lower risk of intraoperative seizures compared with LEV therapy alone in patients with glioma during awake brain mapping. These findings will help neurosurgeons conduct safe and reliable awake surgeries and reduce the rate of intraoperative intractable seizures during such procedures.

Motomura|Kazuya|K| Chalise|Lushun|L| Shimizu|Hiroyuki|H| Yamaguchi|Junya|J| Nishikawa|Tomohide|T| Ohka|Fumiharu|F| Aoki|Kosuke|K| Tanahashi|Kuniaki|K| Hirano|Masaki|M| Wakabayashi|Toshihiko|T| Natsume|Atsushi|A|

intraoperative seizure outcome
levetiracetam
perampanel
glioma
awake surgery
oncology


Haplotypes of the inducible nitric oxide synthase gene are strongly associated with exhaled nitric oxide levels in adults: a population-based study.

Abstract:
BACKGROUND
Previous genetic association studies have reported evidence for association of single-nucleotide polymorphisms (SNPs) in the NOS2 gene, encoding inducible nitric oxide synthase (iNOS), to variation in levels of fractional exhaled nitric oxide (FENO) in children and adults. In this study, we evaluated 10 SNPs in the region of chromosome 17 from 26.07 Mb to 26.13 Mb to further understand the contribution of NOS2 to variation in levels of FENO.

METHODS
In a cohort of 5912 adults 25-75 years of age, we investigated the relationship between NOS2 haplotypes and FENO, and effect modification by asthma.

RESULTS
Seven common (frequency ≥5%) haplotypes (H1-H7) were inferred from all possible haplotype combinations. One haplotype (H3) was significantly associated with lower levels of FENO: -5.8% (95% CI -9.8 to -1.7; p=0.006) compared with the most common baseline haplotype H1. Two haplotypes (H5 and H6) were significantly associated with higher levels of FENO: +10.7% (95% CI 5.0 to 16.7; p=0.0002) and +14.9% (95% CI 10.6 to 19.3; p=7.8×10(-13)), respectively. The effect of haplotype H3 was mainly seen in subjects with asthma (-21.6% (95% CI -33.5 to -5.9)) and was not significant in subjects without asthma (-4.2% (95% CI -8.4 to 0.2)). The p value for interaction between H3 and asthma status was 0.004.

CONCLUSIONS
Our findings suggest that several common haplotypes in the NOS2 gene contribute to variation in FENO in adults. We also saw some evidence of effect modification by asthma status on haplotype H3.

Dahgam|Santosh|S|
Modig|Lars|L|
Torinsson Naluai|Åsa|Å|
Olin|Anna-Carin|AC|
Nyberg|Fredrik|F|

Asthma
Complex traits
Genetic epidemiology


Skeletal dysplasia with craniofacial deformity and disproportionate dwarfism in hair sheep of northeastern Brazil.

Abstract: This paper reports a newly described form of skeletal dysplasia affecting Brazilian hair sheep of the Cabugi breed. This breed is characterized by having a short head and in some cases the animals are smaller and more compact than sheep of similar breeds. Lambs born with craniofacial abnormalities and dwarfism that die at 2-6 months of age are frequent in this breed. In a flock of 68 ewes and three rams of the Cabugi breed, 134 lambs were born over a 4-year period. Of these, 14 (10.4%) had marked cranial abnormalities and dwarfism and died or were humanely destroyed, 43 (32%) had a normal face and 77 (57.5%) had the short face characteristic of the breed. Dwarf lambs were much smaller than normal, with short legs, a domed head with retruded muzzle and protruded mandible, sternal deformities and exophthalmic eyes situated more laterally in the face than normal. Microscopical examination of long bones of the limbs, bones of the base of the skull and vertebrae showed no lesions. Bones from four affected lambs and one control lamb were macerated for morphometric examination. Although the length of the spinal cord was similar, there was disproportionate shortening of the appendicular bones, particularly the distal segments. Thus the disease was defined as a skeletal dysplasia characterized by craniofacial deformity and disproportionate dwarfism. It is suggested that the disease is inherited as an incomplete dominant trait. The shortened face, which is a feature of the Cabugi breed, may represent the heterozygous state and the more severe, often lethal, dwarfism may occur in homozygotes.

Dantas|F P M|FP|
Medeiros|G X|GX|
Figueiredo|A P M|AP|
Thompson|K|K|
Riet-Correa|F|F|

skeletal dysplasia
disproportionate dwarfism
sheep
brachycephaly


Impact of the pneumococcal conjugate vaccine on serotype distribution and susceptibility trends of pediatric non-invasive Streptococcus pneumoniae isolates in Tokai, Japan over a 5-year period.

Abstract: Introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in February 2010 markedly reduced the burden of invasive pneumococcal disease (IPD) and changed serotype distribution in Japan. We investigated the serotype distribution and susceptibility trends of non-invasive Streptococcus pneumoniae isolates collected from pediatric patients. A total of 564 pneumococcal isolates were collected over a 5-year period between 2008 and 2012. The coverage of PCV7 significantly decreased throughout the study period, from 49.3% in period 1 (between June 2008 and April 2009) to 23.4% in period 4 (between October 2011 and March 2012). This change was mainly due to a large decrease in the frequency of 19F (from 20.6% to 9.9%) and 6B (from 10.3% to 2.7%) and an increase in serotype 3 (from 5.1% to 13.5%) and serogroup 15 (from 4.4% to 9.0%). According to serotype replacement, the susceptible ratios of S. pneumoniae to β-lactams increased slightly while macrolide resistance remained high. The high frequency of macrolide-resistant pneumococcal isolates may continue because of the high frequency of erm(B) in replace serotypes such as serotype 3 and serogroup 15. The continuous surveillance study is essential following the introduction of a second generation 13-valent pneumococcal conjugate vaccine (PCV13).

Okade|Hayato|H| Funatsu|Tori|T| Eto|Maki|M| Furuya|Yuri|Y| Mizunaga|Shingo|S| Nomura|Nobuhiko|N| Mitsuyama|Junichi|J| Yamagishi|Yuka|Y| Mikamo|Hiroshige|H|

D000069443:Heptavalent Pneumococcal Conjugate Vaccine

Streptococcus pneumoniae
PCV7
Non-invasive pneumococcal disease


Antibiotic-treated acute appendicitis-reception in social media.

Abstract:
PURPOSE
Social media, especially Twitter®, is becoming increasingly important for medical topics. Systematic analyses of the content of these tweets are rare. To date, no analysis of the reception of antibiotic/non-operative-treated acute appendicitis on Twitter® has been performed.

METHODS
Tweets with the content "appendicitis," "appendix," and "appendectomy" from December 31, 2010, to September 27, 2017, were recorded. Further analysis was performed by secondary search strings related to antibiotic-treated acute appendicitis. Subsequent systematic analysis of content, author groups, and followers was performed.

RESULTS
Out of 22,962 analyzed tweets, 3400 were applicable on all search strings, and 349 dealt meaningfully with antibiotic-treated acute appendicitis. 47.9% of the tweets were published by individuals, of which non-surgical consultants comprised the largest group. The tweets published by organizations and institutions were mostly published by publishing platforms. Half of the tweets were neutral, with an overall positive trend for antibiotic-treated acute appendicitis, but significant differences were noted among the authors. The number of followers showed a wide range, with an considerable numeric impact.

CONCLUSION
The scientific discussion of antibiotic-treated acute appendicitis is reflected on Twitter®. Overall, antibiotic-treated acute appendicitis is presented in a neutral and differentiated manner on Twitter®, but this picture is exclusively derived from assessment of a variety of tweets. Individual tweets are partially undifferentiated in content and misrepresent antibiotic-treated acute appendicitis. In addition, content and intentions are significantly author dependent. Scientists should therefore use Twitter® to make sound medical information heard. If this policy is not implemented, the importance of inadequate and incorrect information transfer is indirectly increased.

Social media
Twitter®
Antibiotics
Appendicitis


Shoe collar height effect on athletic performance, ankle joint kinematics and kinetics during unanticipated maximum-effort side-cutting performance.

Abstract: Side-step cutting manoeuvres comprise the coordination between planting and non-planting legs. Increased shoe collar height is expected to influence ankle biomechanics of both legs and possibly respective cutting performance. This study examined the shoe collar height effect on kinematics and kinetics of planting and non-planting legs during an unanticipated side-step cutting. Fifteen university basketball players performed maximum-effort side-step cutting to the left 45° direction or a straight ahead run in response to a random light signal. Seven successful cutting trials were collected for each condition. Athletic performance, ground reaction force, ankle kinematics and kinetics of both legs were analysed using paired t-tests. Results indicated that high-collar shoes resulted in less ankle inversion and external rotation during initial contact for the planting leg. The high-collar shoes also exhibited a smaller ankle range of motion in the sagittal and transverse planes for both legs, respectively. However, no collar effect was found for ankle moments and performance indicators including cutting performance time, ground contact time, propulsion ground reaction forces and impulses. These findings indicated that high-collar shoes altered ankle positioning and restricted ankle joint freedom movements in both legs, while no negative effect was found for athletic cutting performance.

Lam|Gilbert Wing Kai|GW|
Park|Eun Jung|EJ|
Lee|Ki-Kwang|KK|
Cheung|Jason Tak-Man|JT|

ankle
side-step cutting manoeuvre
planting and non-planting legs
high-collar shoe


A reappraisal of the u.s. Clinical trials of post-treatment lyme disease syndrome.

Abstract:
UNLABELLED
Four federally funded randomized placebo-controlled treatment trials of post-treatment Lyme syndrome in the United States have been conducted. Most international treatment guidelines summarize these trials as having shown no acute or sustained benefit to repeated antibiotic therapy. The goal of this paper is to determine whether this summary con-clusion is supported by the evidence.

METHODS
The methods and results of the 4 U.S. treatment trials are described and their critiques evaluated.

RESULTS
2 of the 4 U.S. treatment trials demonstrated efficacy of IV ceftriaxone on primary and/or secondary outcome measures.

CONCLUSIONS
Future treatment guidelines should clarify that efficacy of IV ceftriaxone for post-treatment Lyme fatigue was demonstrated in one RCT and supported by a second RCT, but that its use was not recommended primarily due to adverse events stemming from the IV route of treatment. While repeated IV antibiotic therapy can be effective, safer modes of delivery are needed.

Fallon|Brian A|BA|
Petkova|Eva|E|
Keilp|John G|JG|
Britton|Carolyn B|CB|

Clinical Trials
Post-treatment Lyme Disease Syndrome
Lyme disease
Chronic Lyme disease
Lyme Encephalopathy
Treatment Guidelines.


Vascular endothelial growth factor driving aberrant keratin expression pattern contributes to the pathogenesis of psoriasis.

Abstract: Psoriasis is a chronic inflammatory skin disease severely affecting patients' physical and psychological well-being. Aberrant keratin expression in psoriasis plays a crucial role in keratinocyte dysfunction and disease development. Little is yet known about the mechanism of this keratin dysregulation. VEGF (Vascular endothelial growth factor) is significantly elevated in psoriatic patients and VEGFRs are detected on keratinocytes, leading to our hypothesis that this keratin dysregulation may be regulated by VEGF. In this study, we showed that VEGFR2 was overexpressed in psoriatic epidermis and was correlated with K (keratin) 6, K16&K17 upregulation and K1&K10 downregulation. VEGF increased both mRNA and protein levels of K6, K16&K17 and decreased those of K1&K10 in NHEKs (normal human epidermal keratinocytes). Further we identified activation of STAT3, ERK1/2, and p38 pathways in VEGF-treated NHEKs. Using specific pathway antagonists and siRNAs we found that VEGF induced K6, K16&K17 via these three pathways and reduced K1&K10 via ERK1/2. Finally, VEGF-induced aberrant keratin expression pattern and epidermal thickening were confirmed in a VEGF-local-injection mouse model. Collectively, we demonstrated that VEGF was associated with aberrant keratin expression pattern in psoriasis and provided a new insight into the role of VEGF in psoriasis pathogenesis, indicating VEGF as a potential therapeutic target.

Jiang|Man|M| Li|Bing|B| Zhang|Jieyu|J| Hu|Lei|L| Dang|Erle|E| Wang|Gang|G|

D042461:Vascular Endothelial Growth Factor A


Association between 25(OH)-vitamin D and testosterone levels: Evidence from men with chronic spinal cord injury.

Abstract:
OBJECTIVE
As an independent linear association between 25-hydroxyvitamin D (25(OH)D) and testosterone levels is controversial, this study aimed to explore this topic in men with chronic spinal cord injury (SCI), who exhibit a high prevalence of both androgen and vitamin D deficiency.

DESIGN
Forty-nine men with chronic SCI consecutively admitted to a rehabilitation program underwent clinical/biochemical evaluations.

RESULTS
Deficiency of 25(OH)D (<20 ng/mL) was found in 36 patients (73.5%). They exhibited significantly lower total testosterone and free testosterone levels, higher parathyroid hormone (PTH) and HOMA-IR, a poorer functional independence degree, and were engaged in poorer weekly leisure time physical activity (LTPA). Significant correlates of 25(OH)D levels were: total testosterone, free testosterone, PTH, functional independence degree and weekly LTPA. At the linear regression models, lower 25(OH)D levels were associated with both lower total and free testosterone after adjustment for age, smoking, alcohol consumption, comorbidities and HOMA-IR. However, after full adjustment, also including functional independence degree, BMI and LTPA, only the association of lower 25(OH)D with lower free testosterone was still significant.

CONCLUSION
In men with SCI, 25(OH)D correlates with total and free testosterone and exhibits an independent linear association with free testosterone. Regardless of this independent link, hypovitaminosis D and androgen deficiency are markers of poor health, sharing common risk factors to take into account in the rehabilitative approach to patients with SCI.

Barbonetti|Arcangelo|A|
Vassallo|Maria Rosaria C|MR|
Felzani|Giorgio|G|
Francavilla|Sandro|S|
Francavilla|Felice|F|

Hypovitaminosis D
Androgen deficiency
Hypogonadism
Paraplegia
Tetraplegia


Empirical Bayes estimation of the selected treatment mean for two-stage drop-the-loser trials: a meta-analytic approach.

Abstract: Point estimation for the selected treatment in a two-stage drop-the-loser trial is not straightforward because a substantial bias can be induced in the standard maximum likelihood estimate (MLE) through the first stage selection process. Research has generally focused on alternative estimation strategies that apply a bias correction to the MLE; however, such estimators can have a large mean squared error. Carreras and Brannath (Stat. Med. 32:1677-90) have recently proposed using a special form of shrinkage estimation in this context. Given certain assumptions, their estimator is shown to dominate the MLE in terms of mean squared error loss, which provides a very powerful argument for its use in practice. In this paper, we suggest the use of a more general form of shrinkage estimation in drop-the-loser trials that has parallels with model fitting in the area of meta-analysis. Several estimators are identified and are shown to perform favourably to Carreras and Brannath's original estimator and the MLE. However, they necessitate either explicit estimation of an additional parameter measuring the heterogeneity between treatment effects or a quite unnatural prior distribution for the treatment effects that can only be specified after the first stage data has been observed. Shrinkage methods are a powerful tool for accurately quantifying treatment effects in multi-arm clinical trials, and further research is needed to understand how to maximise their utility.

D001499:Bayes Theorem
D002986:Clinical Trials as Topic
D006801:Humans
D016013:Likelihood Functions
D015201:Meta-Analysis as Topic
D012107:Research Design
D016896:Treatment Outcome

empirical Bayes estimation
drop-the-loser trials
meta-analysis
temporal coherency


Selective denervation of the corrugator supercilii muscle for the treatment of idiopatic trigeminal neuralgia purely paroxysmal distributed in the supraorbital and suprathrochlear dermatomes.

Abstract:
INTRODUCTION
Idiopatic trigeminal neuralgia purely paroxysmal (ITNp) distributed in the supraorbital and suprathrochlear dermatomes (SSd), refractory to conventional treatments have been linked to the hyperactivity of the corrugator supercilii muscle (CSM). In these patients, the inactivation of the CSM via botulinum toxin type A (BTA) injections has been proven to be safe and effective in reducing migraine burden. The main limitation of BTA is the need of repetitive injections and relative high costs. Based on the study of the motor innervation of the CSM, we describe here an alternative approach to improve these type of migraines, based on a minimally invasive denervation of the CSM.

MATERIALS AND METHODS
Motor innervation and feasibility of selective CSM denervation was first studied on fresh frozen cadavers. Once the technique was safely established, 15 patients were enrolled. To be considered eligible, patients had to meet the following criteria: positive response to BTA treatment, migraine disability assessment score > 24, > 15 migraine days/month, no occipital/temporal trigger points and plausible reasons to discontinue BTA treatment. Pre- and post- operative migraine headache index (MHI) were compared, and complications were classified following the Clavien-Dindo classification (CDC).

RESULTS
Fifteen patients (9 females and 6 males) underwent the described surgical procedure. The mean age was 41 ± 10 years. Migraine headache episodes decreased from 24 ± 4 day/month to 2 ± 2 (p < 0.001) The MHI decreased from 208 ± 35 to 10 ± 11 (p < 0.001). One patient (7%) had a grade I complication according to the CDC. No patient needed a second operative procedure.

CONCLUSIONS
Our findings suggest that the selective CSM denervation represents a safe and minimally invasive approach to improve ITNp distributed in the SSd associated with CSM hyperactivation.

TRIAL REGISTRATION
The data collection was conducted as a retrospective quality assessment study and all procedures were performed in accordance with the ethical standards of the national research committee and the 1964 Helsinki Declaration and its later amendments.

Gualdi|Alessandro|A|
Cambiaso-Daniel|Janos|J|
Gatti|Jonatann|J|
Peled|Ziv M|ZM|
Hagan|Robert|R|
Bertossi|Dario|D|
Wurzer|Paul|P|
Kamolz|Lars-Peter|LP|
Scherer|Saja|S|
Pietramaggiori|Giorgio|G|

Neuralgia
Botulinum toxin type a
Headache disorders
Migraine disorders
Quality of life


Three structurally similar odorants trigger distinct signaling pathways in a mouse olfactory neuron.

Abstract: In the mammalian olfactory system, one olfactory sensory neuron (OSN) expresses a single olfactory receptor gene. By calcium imaging of individual OSNs in intact mouse olfactory turbinates, we observed that a subset of OSNs (Ho-OSNs) located in the most ventral olfactory receptor zone can mediate distinct signaling pathways when activated by structurally similar ligands. Calcium imaging showed that Ho-OSNs were highly sensitive to 2-heptanone, heptaldehyde and cis-4-heptenal. 2-heptanone-evoked intracellular calcium elevation was mediated by cAMP signaling while heptaldehyde triggered the diacylglycerol pathway. An increase of intracellular calcium evoked by cis-4-heptenal was due to a combination of activation mediated by the adenylate cyclase pathway and suppression generated by phospholipase C signaling. Pharmacological studies demonstrated that novel mechanisms were involved in the phospholipase C-mediated intracellular calcium changes. Binary-mixture studies and cross-adaptation data indicate that three odorants acted on the same olfactory receptor. The feature that an olfactory receptor mediates multiple signaling pathways was specific for Ho-OSNs and not established in another population of OSNs characterized. Our study suggests that distinct signaling pathways triggered by ligand-induced conformational changes of an olfactory receptor constitute a complex information process mechanism in olfactory transduction. This study has important implications beyond olfaction in that it provides insights of plasticity and complexity of G-protein-coupled receptor activation and signal transduction.

olfactory neuron
olfactory receptor
calcium imaging
adenylate cyclase
phospholipase C
sensory transduction


Pneumoperitoneum from pneumomediastinum in paraquat poisoning.

Abstract: Pneumomediastinum is not uncommon in paraquat poisoning and usually results from oesophageal perforation or alveolar rupture in fibrotic lung disease. However, the combined presentation of pneumomediastinum and pneumoperitoneum is a rarity. We recently managed a young patient with paraquat ingestion who developed spontaneous pneumomediastinum. His chest radiograph also showed free air under the right hemidiaphragm. This pneumoperitoneum caused no clinical symptom and resolved spontaneously within a few days without any surgical intervention.


Screening for gestational diabetes in the Lombardy region: A population-based study.

Abstract:
AIM
As the treatment of hyperglycaemia during pregnancy with diet or insulin reduces the risk of adverse maternal outcomes and perinatal complications, screening for gestational diabetes mellitus (GDM) is included, albeit to variable extents, in all guidelines of care for pregnant women. The aim of the present investigation was to estimate the proportion of pregnancies screened for GDM in Lombardy between 2007 and 2010, and to identify predictors of screening.

METHODS
A retrospective cross-sectional study using regional healthcare utilization databases of Lombardy was conducted. The study included all residents of Lombardy without pregestational diabetes who delivered between 1 January 2007 and 31 December 2010. The proportion of pregnancies with at least one screening test for GDM was calculated, along with the odds ratios and 95% confidence intervals associated with selected covariates for GDM screening.

RESULTS
Of the 362,818 pregnancies included in the sample, 30% were screened for GDM. The proportion of pregnancies screened increased slightly from 2007 (27%) to 2010 (33%) and with maternal age (from 28% among women<25 years to 32% among those ≥35 years), and varied widely across local health management organizations (HMOs) of residence (range: 20% to 68%). Socioeconomic indicators (education, immigrant status), obstetric history and prepregnancy hypertension were independent predictors of GDM screening.

CONCLUSION
The study finding of a low rate of pregnant women screened for GDM among residents of Lombardy supports the need for programmes to improve training of healthcare professionals, to raise women's awareness of GDM and to eliminate barriers to GDM screening.

Nicotra|F|F|
Molinari|C|C|
Dozio|N|N|
Castiglioni|M T|MT|
Ibrahim|B|B|
Zambon|A|A|
Corrao|G|G|
Scavini|M|M|

D000328:Adult
D001724:Birth Weight
D003430:Cross-Sectional Studies
D016640:Diabetes, Gestational
D005260:Female
D005951:Glucose Tolerance Test
D006801:Humans
D007231:Infant, Newborn
D007558:Italy
D008403:Mass Screening
D011247:Pregnancy
D011256:Pregnancy Outcome
D011296:Prenatal Diagnosis
D012189:Retrospective Studies
D055815:Young Adult

Screening
Gestational diabetes mellitus
Predictors
Cross-sectional study
Healthcare utilization databases
Oral glucose tolerance test


Effects of the β1 auxiliary subunit on modification of Rat Na(v)1.6 sodium channels expressed in HEK293 cells by the pyrethroid insecticides tefluthrin and deltamethrin.

Abstract: We expressed rat Nav1.6 sodium channels with or without the rat β1 subunit in human embryonic kidney (HEK293) cells and evaluated the effects of the pyrethroid insecticides tefluthrin and deltamethrin on whole-cell sodium currents. In assays with the Nav1.6 α subunit alone, both pyrethroids prolonged channel inactivation and deactivation and shifted the voltage dependence of channel activation and steady-state inactivation toward hyperpolarization. Maximal shifts in activation were ~18 mV for tefluthrin and ~24 mV for deltamethrin. These compounds also caused hyperpolarizing shifts of ~10-14 mV in the voltage dependence of steady-state inactivation and increased in the fraction of sodium current that was resistant to inactivation. The effects of pyrethroids on the voltage-dependent gating greatly increased the size of sodium window currents compared to unmodified channels; modified channels exhibited increased probability of spontaneous opening at membrane potentials more negative than the normal threshold for channel activation and incomplete channel inactivation. Coexpression of Nav1.6 with the β1 subunit had no effect on the kinetic behavior of pyrethroid-modified channels but had divergent effects on the voltage-dependent gating of tefluthrin- or deltamethrin-modified channels, increasing the size of tefluthrin-induced window currents but decreasing the size of corresponding deltamethrin-induced currents. Unexpectedly, the β1 subunit did not confer sensitivity to use-dependent channel modification by either tefluthrin or deltamethrin. We conclude from these results that functional reconstitution of channels in vitro requires careful attention to the subunit composition of channel complexes to ensure that channels in vitro are faithful functional and pharmacological models of channels in neurons.

D062557:NAV1.6 Voltage-Gated Sodium Channel

HEK293 cells
Pyrethroid insecticide
Functional reconstitution
Na(v)1.6 isoform
Voltage-gated sodium channel
β Subunits


Multi-Elements in Waters and Sediments of Shallow Lakes: Relationships with Water, Sediment, and Watershed Characteristics.

Abstract: We measured concentrations of multiple elements, including rare earth elements, in waters and sediments of 38 shallow lakes of varying turbidity and macrophyte cover in the Prairie Parkland (PP) and Laurentian Mixed Forest (LMF) provinces of Minnesota. PP shallow lakes had higher element concentrations in waters and sediments compared to LMF sites. Redundancy analysis indicated that a combination of site- and watershed-scale features explained a large proportion of among-lake variability in element concentrations in lake water and sediments. Percent woodland cover in watersheds, turbidity, open water area, and macrophyte cover collectively explained 65.2 % of variation in element concentrations in lake waters. Sediment fraction smaller than 63 µm, percent woodland in watersheds, open water area, and sediment organic matter collectively explained 64.2 % of variation in element concentrations in lake sediments. In contrast to earlier work on shallow lakes, our results showed the extent to which multiple elements in shallow lake waters and sediments were influenced by a combination of variables including sediment characteristics, lake morphology, and percent land cover in watersheds. These results are informative because they help illustrate the extent of functional connectivity between shallow lakes and adjacent lands within these lake watersheds.

Kissoon|La Toya T|TT|
Jacob|Donna L|DL|
Hanson|Mark A|MA|
Herwig|Brian R|BR|
Bowe|Shane E|SE|
Otte|Marinus L|ML|

Shallow lake
Rare earth elements
Redundancy analysis
Land cover
Trace elements


Two-tiered coupling between flowing actin and immobilized N-cadherin/catenin complexes in neuronal growth cones.

Abstract: Neuronal growth cones move forward by dynamically connecting actin-based motility to substrate adhesion, but the mechanisms at the individual molecular level remain unclear. We cultured primary neurons on N-cadherin-coated micropatterned substrates, and imaged adhesion and cytoskeletal proteins at the ventral surface of growth cones using single particle tracking combined to photoactivated localization microscopy (sptPALM). We demonstrate transient interactions in the second time scale between flowing actin filaments and immobilized N-cadherin/catenin complexes, translating into a local reduction of the actin retrograde flow. Normal actin flow on micropatterns was rescued by expression of a dominant negative N-cadherin construct competing for the coupling between actin and endogenous N-cadherin. Fluorescence recovery after photobleaching (FRAP) experiments confirmed the differential kinetics of actin and N-cadherin, and further revealed a 20% actin population confined at N-cadherin micropatterns, contributing to local actin accumulation. Computer simulations with relevant kinetic parameters modeled N-cadherin and actin turnover well, validating this mechanism. Such a combination of short- and long-lived interactions between the motile actin network and spatially restricted adhesive complexes represents a two-tiered clutch mechanism likely to sustain dynamic environment sensing and provide the force necessary for growth cone migration.

Garcia|Mikael|M| Leduc|Cécile|C| Lagardère|Matthieu|M| Argento|Amélie|A| Sibarita|Jean-Baptiste|JB| Thoumine|Olivier|O|

D036681:Fluorescence Recovery After Photobleaching

growth cone
micropatterned substrates
actin flow
N-cadherin adhesion
single-molecule tracking


Implementation of participatory organizational change in long term care to improve safety.

Abstract:
INTRODUCTION
Long Term Care (LTC) facilities are fast-paced, demanding environments placing workers at significant risk for injuries. Health and safety interventions to address hazards in LTC are challenging to implement. The study assessed a participatory organizational change intervention implementation and impacts.

METHODS
This was a mixed methods implementation study with a concurrent control, conducted from 2017 to 2019 in four non-profit LTC facilities in Ontario, Canada. Study participants were managers and frontline staff. Intervention sites implemented a participatory organizational change program, control sites distributed one-page health and safety pamphlets. Program impact data were collected via Survey (self-efficacy, control over work, pain and general health) and observation (Quick Exposure Checklist). Interviews/focus groups were used to collect program implementation data.

RESULTS
Participants described program impacts (hazard controls through equipment purchase/modification, practice changes, and education/training) and positive changes in culture, communication and collaboration. There was a statistically significant difference in manager self-efficacy for musculoskeletal disorder (MSD) hazards between the control and intervention sites over time but no other statistical differences were found. Key program implementation challenges included LTC hazards, staff shortage/turnover, safety culture, staff time to participate, and communication. Facilitators included frontline staff involvement during implementation, management support, focusing on a single unit, training, and involving an external program facilitator.

CONCLUSION
A participatory program can have positive impacts on identifying and reducing MSD hazards. Key to success is involving frontline staff in identifying hazards and creating solutions and management encouragement on a unit working together. High turnover rates, staffing shortages, and time constraints were barriers as they are for all organizational change efforts in LTC. The implementation findings are likely applicable in any jurisdiction. Practical Application: Implementing a participatory organizational change program to reduce MSD hazards is feasible in LTC and can improve communication and aid in identification and control of hazards.

Van Eerd|Dwayne|D|
D'Elia|Teresa|T|
Ferron|Era Mae|EM|
Robson|Lynda|L|
Amick|Benjamin|B|

D017144:Focus Groups
D006801:Humans
D008134:Long-Term Care
D009864:Ontario
D009936:Organizational Innovation
D017751:Safety Management

Implementation
Long term care
Hazard reduction
Participatory ergonomics


Comparative study of diclofenac-induced embryotoxicity and teratogenesis in Xenopus laevis and Lithobates catesbeianus, using the frog embryo teratogenesis assay: Xenopus (FETAX).

Abstract: Water is an increasingly deteriorated, limited natural resource due to population increase and industrialization. Also, the widespread use of pharmaceuticals in modern society leads to their presence in domestic, hospital and industrial effluents. Due to their analgesic properties, some of the most commonly used pharmaceuticals are nonsteroidal anti-inflammatory drugs (NSAIDs). High concentrations of one these products, diclofenac (DCF), have been detected in effluents and water bodies of different countries, including Mexico. Diverse studies show that trace amounts (ngL-1 to μgL-1) of this compound induce toxicity on aquatic organisms such as algae, microcrustaceans and fish. However, studies on its potential toxicity during development in species of commercial interest such as the American bullfrog Lithobates catesbeianus are scarce. The present study aimed to evaluate DCF-induced teratogenesis and embryotoxicity in Xenopus laevis and L. catesbeianus, a species marketed as a nutritional meat source in Mexico, using the frog embryo teratogenesis assay: Xenopus (FETAX). Oocytes in mid-blastula transition were exposed for 96h to 1, 4, 8, 16, 32 and 62.5mgDCFL-1. The criteria evaluated were mortality, malformation and growth inhibition. The teratogenic index was 4.2 in L. catesbeianus, three-fold higher than the reference limit (1.5), and 3.9 in X. laevis. Diclofenac induced diverse malformations in both species, the most frequent of these being axial malformations in the tail and notochord, edema and stunted growth. Results indicate that DCF is a potentially teratogenic compound and is toxic during development in X. laevis and L. catesbeianus, a species which, due to its sensitivity, can be used to evaluate the toxicity of pharmaceutical products, using FETAX.

Cardoso-Vera|Jesús Daniel|JD|
Islas-Flores|Hariz|H|
SanJuan-Reyes|Nely|N|
Montero-Castro|Elena Irabella|EI|
Galar-Martínez|Marcela|M|
García-Medina|Sandra|S|
Elizalde-Velázquez|Armando|A|
Dublán-García|Octavio|O|
Gómez-Oliván|Leobardo Manuel|LM|


Dipyrone comedication in aspirin treated stroke patients impairs outcome.

Abstract:
BACKGROUND
>50% of stroke patients rely on analgesic medication to control pain. Aspirin is the mainstay of medical treatment of stroke patients; however analgesic medication with dipyrone impairs aspirin antiplatelet effects ex-vivo. The clinical impact of this impairment is unknown. Therefore, we aimed to determine aspirin antiplatelet effects and neurological outcome in stroke patients with aspirin and dipyrone comedication.

METHODS
We conducted a prospective cohort study in 41 patients with stroke. Primary outcome was pharmacodynamic response to aspirin in dipyrone treated stroke patients. Secondary outcome was neurological recovery after stroke. Pharmacodynamic response to aspirin was measured using arachidonic acid induced aggregation in light-transmission aggregometry. Neurological outcome was determined three months after stroke onset by telephone interview.

RESULTS
Patient's characteristics were similar in the aspirin-alone group and the aspirin+dipyrone group. Impaired pharmacodynamic response to aspirin occurred in 62% (14/21) of patients with aspirin and dipyrone co-medication. Only 10% (2/20) of aspirin treated patients without analgesic comedication displayed residual platelet reactivity (P=0.001; odds ratio [OR], 18 [95% CI, 3.2-100]). Excellent neurological recovery (measured by three months follow-up modified Rankin Scale<2) was observed in 80% (16/20) of patients in the aspirin-alone group and 48% (10/21) of patients in the aspirin+dipyrone group (P=0.037; OR, 4.4 [95% CI, 1.1-17.7]).

CONCLUSIONS
Dipyrone comedication in patients with stroke impairs pharmacodynamic response to aspirin. This is associated with worse clinical outcome. Therefore dipyrone should be used with caution in aspirin treated stroke patients.

CLINICAL TRIAL REGISTRATION
https://clinicaltrials.gov/show/NCT02148939; Identifier: NCT02148939.

Dannenberg|Lisa|L| Erschoff|Vladimir|V| Bönner|Florian|F| Gliem|Michael|M| Jander|Sebastian|S| Levkau|Bodo|B| Kelm|Malte|M| Hohlfeld|Thomas|T| Zeus|Tobias|T| Polzin|Amin|A|

Dipyrone
Aspirin
Stroke
Pharmacology
Platelet activation
Platelet aggregation


Teachers' Perceptions of Using Health Disparities Content to Engage High Schoolers in Urban Communities.

Abstract: The objective of this study was to report on teachers' perceptions of using health disparities content to engage high school students in urban communities over the course of a summer health disparities professional development (PD) program. Teachers participated in a three-week, 80-hour summer PD, where they received content on health disparities, met with health disparities researchers, and developed project-based learning units focused on health disparities. To under-stand teachers' perceptions of integrating health disparities content in the classroom, thematic coding was used to analyze data from focus groups collected before and after summer PD for three cohorts of high school teachers in two urban school districts (2016-2018, N=22 teachers). Findings were that: 1) Teachers showed awareness of the social challenges students face, even prior to starting a summer PD on health disparities; 2) Teachers appreciated the role of community engagement and student activism as a solution to health disparities and felt that they would be able to engage students with this material; 3) Teachers needed resources, mostly in the form of community connections, to fully integrate health disparities lessons, with community engagement infused throughout. Findings suggest that teachers are prepared to integrate information about community context in their classes and could be furthered empowered to teach about health disparities with the right community connections and engagement infrastructure.

Ramaswamy|Megha|M|
Lumpkins|Crystal|C|
Luaces|Maria Alonso|MA|
Chang|Karin|K|
Cupertino|Paula|P|

Health Disparities
High School
Professional Development


The clinical characteristics of posttraumatic epilepsy following moderate-to-severe traumatic brain injury in children.

Abstract:
PURPOSE
Children with traumatic brain injury (TBI) are at increased risk of posttraumatic epilepsy (PTE); the risk increases according to TBI severity. We examined the long-term incidence and risk factors for developing PTE in a cohort of children hospitalised at one medical centre with moderate or severe TBI.

METHODS
Moderate brain injury was classified as Glasgow Coma Score on Arrival (GCSOA) of 9-13, and severe brain injury as GCSOA ≤8. We collected demographics and clinical data from medical records and interviewed patients and parents at 5-11 years following the TBI event.

RESULTS
During a median follow-up period of 7.3 years, 9 (9%) of 95 children with moderate-to-severe TBI developed PTE; 4 developed intractable epilepsy. The odds for developing PTE was 2.9 in patients with severe compared to moderate TBI. CT findings showed fractures in 7/9 (78%) of patients with PTE, compared to 40/86 (47%) of those without PTE (p = 0.09). Of the patients with fractures, all those with PTE had additional features on CT (such as haemorrhage, contusion and mass effect), compared to 29/40 (73%) of those without PTE. One of nine (11%) PTE patients and 10 of 86 (12%) patients without PTE had immediate seizures. Two (22%) children with PTE had their first seizure more than 2 years after the TBI.

CONCLUSION
Among children with moderate or severe TBI, the presence of additional CT findings, other than skull fractures, seem to increase the risk of PTE. In our cohort, the occurrence of an early seizure did not confer an increased risk of PTE.

Keret|Amit|A| Shweiki|Moatasim|M| Bennett-Back|Odeya|O| Abed-Fteiha|Fadia|F| Matoth|Israel|I| Shoshan|Yigal|Y| Benifla|Mony|M|

Traumatic brain injury
Children
Paediatric neurosurgery
Post-traumatic epilepsy