Arterial vascular access complication in osteogenesis imperfecta.

Abstract: We present a case of the catastrophic bleeding from the femoral access site after an uncomplicated puncture in a patient with Type 1 osteogenesis imperfecta (OI) undergoing coronary angiogram via the femoral route. This had to be treated with a covered stent at the puncture site. This is an extremely rare complication in OI. The potential pathological mechanisms of this complication are discussed. An interventionist will rarely encounter such a patient in the catheterisation laboratory but would do well to be aware of this potential complication.

Osteogenesis imperfecta
coronary angiogram
angioplasty
collagen vascular disease
femoral artery
percutaneous coronary intervention


Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells.

Abstract: Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. COX-2(+) TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2(+) TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy.

Li|Hongzhong|H| Yang|Bing|B| Huang|Jing|J| Lin|Yong|Y| Xiang|Tingxiu|T| Wan|Jingyuan|J| Li|Hongyuan|H| Chouaib|Salem|S| Ren|Guosheng|G|

D015972:Gene Expression Regulation, Neoplastic

D020133:Reverse Transcriptase Polymerase Chain Reaction

cyclooxygenase-2
macrophages
breast cancer
prostaglandin E2
tumor microenvironment


Clinical Outcome and Safety of Transcaval Access for Transcatheter Aortic Valve Replacement as Compared to Other Alternative Approaches.

Abstract: Background: A small proportion of patients in need of transcatheter aortic valve replacement (TAVR) are not suitable for the transfemoral approach due to peripheral artery disease. Alternative TAVR approaches are associated with short- and long-term hazards. A novel technique of caval-aortic (transcaval) access for TAVR has been utilized as an alternative access technique. Aim: To compare safety and efficacy of transcaval access as compared to other alternative access (axillary or apical) for TAVR. Methods: A single-center, retrospective analysis of consecutive patients undergoing alternative access for TAVR. Events were adjudicated according to VARC-2 criteria. Results: A total of 185 patients were included in the present analysis. Mean age was 81 years with a small majority for male gender (54%). Of the entire cohort, 20 patients (12%) underwent transcaval TAVR, and 165 patients (82%) underwent TAVR using alternative access. Overall, baseline characteristics were comparable between the two groups. General anesthesia was not utilized in transcaval patients; however, it was routinely used in nearly all alternative access patients. TAVR device success was comparable between the two groups (95%). Acute kidney injury occurred significantly less frequently among transcaval patients as compared to alternative access patients (5 vs. 12%, p = 0.05). Hospital stay was shorter for transcaval patients (6.3 days vs. 14.4; p < 0.001). No difference in early or 30-day mortality (10 vs. 7.9%, p = 0.74) was noted between groups. Conclusions: In patients who cannot undergo TAVR via the trans-femoral approach due to peripheral vascular disease, transcaval access is a safe approach as compared to other alternative access techniques, with lower risk of kidney injury and shorter hospital stay.

Barbash|Israel M|IM|
Segev|Amit|A|
Berkovitch|Anat|A|
Fefer|Paul|P|
Maor|Elad|E|
Elian|Dan|D|
Regev|Ehud|E|
Guetta|Victor|V|

transcaval access
transcatheter aortic valve replacement
aortic stenosis
arterial access
transapical access
transaxillary access


Performance and Cost-Effectiveness of Short Pitch-Based Carbon Fiber Reinforced Mortar Composite.

Abstract: This paper discusses the performance of the short pitch-based carbon fiber reinforced mortar (CFRM) composite considering its key properties and cost-effectiveness. Five different types of mortar composite were produced using 0-4% volume contents of short pitch-based carbon fibers. The mortar composites were tested for inverted slump cone flow (flow time and volume flow), unit weight, air content, compressive strength, flexural strength, impact resistance, and water absorption. The cost-effectiveness of CFRM was assessed based on the performance to cost ratio (PCR), which was calculated for each mortar composite, considering its workability, mechanical properties, and durability. The inverted slump cone volume flow was counted as a measure of workability, whereas the compressive strength, flexural strength, and impact resistance were considered as the major attributes of the mechanical behavior. In addition, the water absorption was used as a measure of durability. The test results revealed that the mortar composite made with 3% carbon fibers provided adequate workability, a relatively high unit weight and low air content, the highest compressive strength, excellent flexural strength, good impact resistance, and the lowest water absorption. It was also found that the PCR increased up to 3% carbon fibers. Beyond a 3% fiber content, the PCR significantly decreased. The overall research findings revealed that the mortar with 3% carbon fibers was the optimum and most cost-effective mortar composite.

carbon fibers
mortar
inverted slump cone flow
unit weight
air content
compressive strength
flexural strength
impact resistance
water absorption
performance to cost ratio


Psychosocial impairment in DSM-5 intermittent explosive disorder.

Abstract: The purpose of this study was to document the functional severity of DSM-5 IED in a clinical research sample. IED and control groups were compared on psychosocial functioning, life satisfaction, and on a variety of cognitive and behavioral issues. IED study participants reported significantly worse psychosocial function, quality of life, and higher job dysfunction than both psychiatric and healthy control study participants. The presence of DSM-5 IED is associated with significant psychosocial and functional impairment. Early intervention may aid in minimizing the consequences of impulsive aggressive behavior, and improving psychosocial functioning and quality of life.

D039721:Diagnostic and Statistical Manual of Mental Disorders

D007174:Disruptive, Impulse Control, and Conduct Disorders

IED
Psychosocial function
Life satisfaction


Mechanism underlying anti-hyperalgesic and anti-allodynic properties of anomalin in both acute and chronic inflammatory pain models in mice through inhibition of NF-κB, MAPKs and CREB signaling cascades.

Abstract: The numerous mediators of pain and inflammation are products of injury-induced gene expression that lead to changes in the nervous system and immune responses. These multiple molecules and mechanisms suggest novel strategies that could be used for analgesic drug development. The present study investigated the possible anti-hyperalgesic effects of anomalin in complete Freund's adjuvant (CFA)-induced acute and chronic inflammatory pain models. Acute pretreatment of mice with anomalin (10 and 50mg/kg, i.p.) produced a significant anti-nociceptive effect against CFA- and carrageenan-induced mechanical hyperalgesia and allodynia. In a chronic pain model, administration of anomalin inhibited CFA-induced hyperalgesia, and it did not cause any apparent toxicity. Another set of experiments observed that anomalin inhibited CFA- and carrageenan-induced paw edema in acute and chronic models. To elucidate the molecular mechanism underlying the anti-nociceptive effect of anomalin, the various pain signaling pathways [NF-κB, cAMP response element-binding protein (CREB), and mitogen activated protein kinase (MAPKs)/AP-1] that are involved were examined. Intraperitoneal (i.p.) pretreatment of anomalin exhibited potent inhibitory effects on direct mediators of hyperalgesia (iNOS and COX-2). The release of CFA-induced plasma nitrite and paw tissue hyperalgesic cytokine (TNF-α) was reduced remarkably. In addition, the adenosine 5'-triphosphate (ATP) in plasma and substance P (SP) in paw tissue were markedly suppressed by anomalin. These results demonstrate that anomalin exhibits an analgesic effect in a consistent manner and that its mechanisms involve the inhibition of the NF-κB, CREB, and MAPKs/AP-1 signaling pathways.

Khan|Salman|S|
Shehzad|Omer|O|
Chun|Jaemoo|J|
Kim|Yeong Shik|YS|

D017362:Cyclic AMP Response Element-Binding Protein

D015971:Gene Expression Regulation, Enzymologic

Anomalin NF-κB MAPK CREB Hyperalgesia Allodynia


Self-assessment of postoperative scars in living liver donors.

Abstract:
BACKGROUND
The application of less invasive techniques for liver surgery in patients undergoing living donor hepatectomy (LDH) has been reported. The objective of this study was to evaluate physical status according to type of incision in donors.

METHODS
One hundred and forty-seven living liver donors underwent hepatectomy using three types of incisions: (i) Mercedes-Benz incision (M.B.), (ii) right subcostal incision with midline up to xiphoid incision (S.C.), and (iii) short upper midline incision (U.M.). A total of 100 donors answered the questionnaires, and 87 had sufficient data for the analyses. An original questionnaire designed to evaluate the physical status concerning postoperative scars. The questionnaire consisted of three major categories: appearance, sensation, and daily activities. The univariate analysis was performed using the chi-square test.

RESULTS
Numbness of the abdominal wall was reported more frequently by the donor with M.B.s and right subcostal incisions up to xiphoid incisions. In terms of appearance, sensation, and daily activities, LDH with a U.M. was found to have a good self-assessment compared with that performed using other types of incisions.

CONCLUSIONS
LDH with a U.M. is a preferable procedure in terms of physical status and safety.

Imamura|Hajime|H| Soyama|Akihiko|A| Takatsuki|Mitsuhisa|M| Muraoka|Izumi|I| Hara|Takanobu|T| Yamaguchi|Izumi|I| Tanaka|Takayuki|T| Kinoshita|Ayaka|A| Kuroki|Tamotsu|T| Eguchi|Susumu|S|

self-assessment
upper midline incision
questionnaire
body image
living donor liver transplantation


Primary Giant Hydatid Cyst of Lumbar Paraspinal Muscles.

Abstract:
BACKGROUND
Hydatid cyst disease, commonly caused by Echinococcus granulosus, rarely occurs in paraspinal muscles. Among the few reported cases, the current case is the largest paraspinal hydatid cyst disease ever reported in literature with a review of management of such large lesions.

CASE DESCRIPTION
A 38-year-old male presented with lower back swelling for 1 year. Ultrasonography and magnetic resonance imaging scans suggested hydatidosis, following which the patient was taken up for surgery after preoperative medical therapy. En bloc resection was done, and histopathologic examination of the resected specimen confirmed the diagnosis. Postoperative albendazole was also used, and no recurrence was noted at 24 months post operation.

CONCLUSIONS
Hydatid disease should be kept as one of the differential diagnoses for back swelling, especially in endemic regions. Giant-sized hydatid cysts of paraspinal muscles, though rare, cannot be ruled out on clinical ground alone. Thorough history taking and detailed examination should be aided with radiologic investigations like magnetic resonance imaging for an accurate diagnosis. En bloc excision of the cyst combined with preoperative and postoperative medical therapy is an effective method of treating this condition and significantly reducing complication rates.

Singh|Sudeep|S| Kalra|Gagan|G| Gupta|Vipin|V| Gupta|Soumya|S|

Paraspinal muscles
En bloc resection
Management of muscular hydatidosis
Muscular hydatidosis
Paraspinal mass
Primary hydatid cyst


Differences in the skeletal muscle transcriptome profile associated with extreme values of fatty acids content.

Abstract:
BACKGROUND
Lipids are a class of molecules that play an important role in cellular structure and metabolism in all cell types. In the last few decades, it has been reported that long-chain fatty acids (FAs) are involved in several biological functions from transcriptional regulation to physiological processes. Several fatty acids have been both positively and negatively implicated in different biological processes in skeletal muscle and other tissues. To gain insight into biological processes associated with fatty acid content in skeletal muscle, the aim of the present study was to identify differentially expressed genes (DEGs) and functional pathways related to gene expression regulation associated with FA content in cattle.

RESULTS
Skeletal muscle transcriptome analysis of 164 Nellore steers revealed no differentially expressed genes (DEGs, FDR 10%) for samples with extreme values for linoleic acid (LA) or stearic acid (SA), and only a few DEGs for eicosapentaenoic acid (EPA, 5 DEGs), docosahexaenoic acid (DHA, 4 DEGs) and palmitic acid (PA, 123 DEGs), while large numbers of DEGs were associated with oleic acid (OA, 1134 DEGs) and conjugated linoleic acid cis9 trans11 (CLA-c9t11, 872 DEGs). Functional annotation and functional enrichment from OA DEGs identified important genes, canonical pathways and upstream regulators such as SCD, PLIN5, UCP3, CPT1, CPT1B, oxidative phosphorylation mitochondrial dysfunction, PPARGC1A, and FOXO1. Two important genes associated with lipid metabolism, gene expression and cancer were identified as DEGs between animals with high and low CLA-c9t11, specifically, epidermal growth factor receptor (EGFR) and RNPS.

CONCLUSION
Only two out of seven classes of molecules of FA studied were associated with large changes in the expression profile of skeletal muscle. OA and CLA-c9t11 content had significant effects on the expression level of genes related to important biological processes associated with oxidative phosphorylation, and cell growth, survival, and migration. These results contribute to our understanding of how some FAs modulate metabolism and may have protective health function.

Cesar|Aline S M|AS|
Regitano|Luciana C A|LC|
Poleti|Mirele D|MD|
Andrade|Sónia C S|SC|
Tizioto|Polyana C|PC|
Oliveira|Priscila S N|PS|
Felício|Andrezza M|AM|
do Nascimento|Michele L|ML|
Chaves|Amália S|AS|
Lanna|Dante P D|DP|
Tullio|Rymer R|RR|
Nassu|Renata T|RT|
Koltes|James E|JE|
Fritz-Waters|Eric|E|
Mourão|Gerson B|GB|
Zerlotini-Neto|Adhemar|A|
Reecy|James M|JM|
Coutinho|Luiz L|LL|

Lipids
Bos indicus
Global Oxidative Metabolism
Human Health
RNA-Seq


The adaptation of everyday practices in the adoption of chronic illness.

Abstract: This article uses social practice theory to examine the role of information-seeking in the maintenance of existing lifestyle and illness-related adjustments in the context of chronic illnesses. The research findings are derived from a thematic analysis of 16 semi-structured in-depth interviews with Estonian Parkinson's disease patients. The coding scheme bases on the four practice elements outlined by Schatzki (practical understandings, rules, teleological structures and general understandings) and other categories related to chronic illness self-management skills, bodily movements, daily routines and information-seeking practices. The findings reveal that people with chronic illness value maintaining their existing lifestyles as long as possible and the willingness to seek out illness-related information is related to the severity and duration of the disease. These findings suggest that effective illness-related communication that supports self-management should provide patients with possibilities to adjust and switch between practices in a time and a pace that is natural and acceptable to them.

D000222:Adaptation, Physiological
D000223:Adaptation, Psychological
D000368:Aged
D000369:Aged, 80 and over
D002908:Chronic Disease
D015331:Cohort Studies
D004957:Estonia
D005260:Female
D015577:Geriatric Assessment
D006801:Humans
D007407:Interviews as Topic
D008019:Life Style
D008297:Male
D010300:Parkinson Disease
D011788:Quality of Life
D000073278:Self-Management
D012720:Severity of Illness Index
D066269:Social Theory

chronic illness
social practice theory
existing lifestyle
self-management
Parkinson’s disease


Withdrawal of Temporary Mechanical Circulatory Support in Patients With Capacity.

Abstract:
CONTEXT
Little is known about the real-time decision-making process of patients with capacity to choose withdrawal of temporary mechanical circulatory support (MCS).

OBJECTIVES
To assess how withdrawal of temporary MCS occurs when patients possess the capacity to make this decision themselves.

METHODS
This retrospective case series included adults supported by CentriMag Acute Circulatory Support or Veno-Arterial Extracorporeal Membrane Oxygenation from February 2, 2007 to May 27, 2020 at a tertiary academic medical center who possessed capacity to participate in end-of-life discussions. Authors performed chart review to determine times between "initiation of temporary MCS," "determination of 'bridge to nowhere,'" "patient expressing desire to withdraw," "agreement to withdraw," "withdrawal," and "death," as well as reasons for withdrawal and the role of ethics, psychiatry, and palliative care.

RESULTS
A total of 796 individuals were included. MCS was withdrawn in 178 (22.4%) of cases. Six of these 178 patients (3.4%) possessed the capacity to decide to withdraw MCS. Time between "patient expressing desire to withdraw" and "agreement to withdraw" ranged from 0 to 3 days; time between "agreement to withdraw" and "withdrawal" ranged from 0 to 6 days. Common reasons for withdrawal include perceived decline in quality of life or low probability of recovery. Ethics and psychiatry were consulted in 3 of 6 cases and palliative care in 5 of 6 cases.

CONCLUSION
While it is rare for patients on MCS to request withdrawal, such cases provide insight into reasons for withdrawal and the important roles of multidisciplinary teams in helping patients and families through end-of-life decision-making.

Carey|Matthew R|MR|
Tong|Wendy|W|
Godfrey|Sarah|S|
Takeda|Koji|K|
Nakagawa|Shunichi|S|

mechanical circulatory support
capacity
decision-making
end-of-life
palliative care
Withdrawal of life support


Development and psychometric evaluation of the ICIQ-LTCqol: A self-report quality of life questionnaire for long-term indwelling catheter users.

Abstract:
AIMS
Long-term indwelling catheterisation may affect health related quality of life, but clinical assessment and monitoring of people with indwelling catheters is poorly recorded because there are no validated measures to capture these criteria. In this paper, we describe the development of the ICIQ-Long Term Catheter quality of life (ICIQ-LTCqol), one of the modules of the ICIQ series, an international project to standardise assessment of lower pelvic dysfunction: www.iciq.net.

METHODS
In-depth interviews were conducted with 27 catheter-users and 4 informal carers and cognitive debriefing with a further 31 catheter-users and clinical experts to evaluate clarity and comprehensiveness. The draft 44 item questionnaire was then sent by post to 893 long-term catheter-users; the 370 completed questionnaires were used to test content validity, test re-test reliability and internal consistency (Cronbach α coefficient). Factor analysis alongside expert opinion was used to formulate the final questionnaire of 16 items. This was then sent by post to another 438 long-term catheter-users to evaluate domain scores.

RESULTS
The final questionnaire consists of two scored domains: catheter function and concern (9 items) and lifestyle impact (3 items) and four standalone items, relating to pads, pain, sexual activity and bladder spasm. Levels of missing data are good (mean 3.6%) with moderate to good agreement and acceptable internal consistency (Cronbach's alpha 0.76 and 0.74 for each domain respectively), suggesting acceptability and stability of the questionnaire.

CONCLUSION
The ICIQ-LTCqol is a psychometrically robust self-report questionnaire for the clinical assessment and evaluation of health related quality of life for long-term catheter users.

Cotterill|Nikki|N|
Fowler|Sarah|S|
Avery|Miriam|M|
Cottenden|Alan M|AM|
Wilde|Mary|M|
Long|Adele|A|
Fader|Mandy J|MJ|

D000203:Activities of Daily Living
D000223:Adaptation, Psychological
D000328:Adult
D000368:Aged
D000369:Aged, 80 and over
D002408:Catheters, Indwelling
D004867:Equipment Design
D005163:Factor Analysis, Statistical
D005260:Female
D006801:Humans
D008297:Male
D008875:Middle Aged
D011594:Psychometrics
D011788:Quality of Life
D015203:Reproducibility of Results
D011795:Surveys and Questionnaires
D013997:Time Factors
D014546:Urinary Catheterization
D062885:Urinary Catheters
D014549:Urinary Incontinence

psychometrics
quality of life
questionnaires
catheter
urinary incontinence


Emerging Approaches for Validating and Managing Multiple Sclerosis Relapse.

Abstract: The autoimmune disease multiple sclerosis (MS) is characterized by relapses in the majority of patients. A definitive clinical diagnosis of relapse in MS can be complicated by the presence of an infection or comorbid disorder. In this mini-review, we describe efforts to develop enhanced imaging techniques and biomarker detection as future tools for relapse validation. There is emerging evidence of roles for meningeal inflammation, sex hormones, comorbid metabolic or mood disorders, and a dysregulated immune profile in the manifestation and severity of relapse. Specific subsets of immune cells likely drive the pathophysiology of relapse, and identification of a patient's unique immunological signature of relapse may help guide future diagnosis and treatment. Finally, these studies highlight the diversity in terms of relapse presentation, immunological signature, and response in patients with MS, indicating that going forward the best approach to assessment and treatment of relapse will be multifactorial and highly personalized.

Mills|Elizabeth A|EA|
Mirza|Ali|A|
Mao-Draayer|Yang|Y|

comorbidity
biomarker
cortical lesion
estrogen
pseudo-relapse


In patients with severe uncontrolled asthma, does knowledge of adherence and inhaler technique using electronic monitoring improve clinical decision making? A protocol for a randomised controlled trial.

Abstract:
INTRODUCTION
Many patients with asthma remain poorly controlled despite the use of inhaled corticosteroids and long-acting beta agonists. Poor control may arise from inadequate adherence, incorrect inhaler technique or because the condition is refractory. Without having an objective assessment of adherence, clinicians may inadvertently add extra medication instead of addressing adherence. This study aims to assess if incorporating objectively recorded adherence from the Inhaler Compliance Assessment (INCA) device and lung function into clinical decision making provides more cost-effective prescribing and improves outcomes.

METHODS AND ANALYSIS
This prospective, randomised, multicentre study will compare the impact of using information on adherence to influence asthma treatment. Patients with severe uncontrolled asthma will be included. Data on adherence, inhaler technique and electronically recorded peak expiratory flow rate will be used to promote adherence and guide a clinical decision protocol to guide management in the active group. The control group will receive standard inhaler and adherence education. Medications will be adjusted using a protocol based on Global Initiativefor Asthma (GINA) recommendations. The primary outcome is the between-group difference in the proportion of patients who have refractory disease and are prescribed appropriate medications at the end of 32 weeks. A co-primary outcome is the difference between groups in the rate of adherence to salmeterol/fluticasone inhaler over the last 12 weeks. Secondary outcomes include changes in symptoms, lung function, type-2 cytokine biomarkers and clinical outcomes between both groups. Cost-effectiveness and cost-utility analyses of the INCA device intervention will be performed. The economic impact of a national implementation of the INCA-SUN programme will be evaluated.

ETHICS AND DISSEMINATION
The results of the study will be published as a manuscript in peer-reviewed journals. The study has been approved by the ethics committees in the five participating hospitals.

TRIAL REGISTRATION
NCT02307669; Pre-results.

Mokoka|Matshediso C|MC|
Lombard|Lorna|L|
MacHale|Elaine M|EM|
Walsh|Joanne|J|
Cushen|Breda|B|
Sulaiman|Imran|I|
Carthy|Damien Mc|DM|
Boland|Fiona|F|
Doyle|Frank|F|
Hunt|Eoin|E|
Murphy|Desmond M|DM|
Faul|John|J|
Butler|Marcus|M|
Hetherington|Kathy|K|
Mark FitzGerald|J|J|
Boven|Job Fm van|JFV|
Heaney|Liam G|LG|
Reilly|Richard B|RB|
Costello|Richard W|RW|

D007722:Health Knowledge, Attitudes, Practice

severe uncontrolled asthma
adherence
INCA electronic monitor
inhaler technique.
randomisedcontrolled trial


Annual rhythms in adults' lifestyle and health (ARIA): protocol for a 12-month longitudinal study examining temporal patterns in weight, activity, diet, and wellbeing in Australian adults.

Abstract:
BACKGROUND
Almost one in three Australian adults are now obese, and the rate continues to rise. The causes of obesity are multifaceted and include environmental, cultural and lifestyle factors. Emerging evidence suggests there may be temporal patterns in weight gain related, for example, to season and major festivals such as Christmas, potentially due to changes in diet, daily activity patterns or both. The aim of this study is to track the annual rhythm in body weight, 24 h activity patterns, dietary patterns, and wellbeing in a cohort of Australian adults. In addition, through data linkage with a concurrent children's cohort study, we aim to examine whether changes in children's body mass index, activity and diet are related to those of their parents.

METHODS
A community-based sample of 375 parents aged 18 to 65 years old, residing in or near Adelaide, Australia, and who have access to a Bluetooth-enabled mobile device or a computer and home internet, will be recruited. Across a full year, daily activities (minutes of moderate to vigorous physical activity, light physical activity, sedentary behaviour and sleep) will be measured using wrist-worn accelerometry (Fitbit Charge 3). Body weight will be measured daily using Fitbit wifi scales. Self-reported dietary intake (Dietary Questionnaire for Epidemiological Studies V3.2), and psychological wellbeing (WHOQOL-BREF and DASS-21) will be assessed eight times throughout the 12-month period. Annual patterns in weight will be examined using Lowess curves. Associations between changes in weight and changes in activity and diet compositions will be examined using repeated measures multi-level models. The associations between parent's and children's weight, activity and diet will be investigated using multi-level models.

DISCUSSION
Temporal factors, such as day type (weekday or weekend day), cultural celebrations and season, may play a key role in weight gain. The aim is to identify critical opportunities for intervention to assist the prevention of weight gain. Family-based interventions may be an important intervention strategy.

TRIAL REGISTRATION
Australia New Zealand Clinical Trials Registry, identifier ACTRN12619001430123 . Prospectively registered on 16 October 2019.

Curtis|Rachel G|RG|0000-0002-1341-7804
Olds|Timothy|T|
Fraysse|François|F|
Dumuid|Dorothea|D|
Hendrie|Gilly A|GA|
Esterman|Adrian|A|
Brown|Wendy J|WJ|
Ferguson|Ty|T|
Lagiseti|Rajini|R|
Maher|Carol A|CA|

Weight
Diet
Obesity
Physical activity
Sedentary behaviour
Sleep
Epidemiology
Compositional data
Overweight


Asiatic Callosciurus squirrels as seed dispersers of exotic plants in the Pampas.

Abstract: Seed dispersal by exotic mammals exemplifies mutualistic interactions that can modify the habitat by facilitating the establishment of certain species. We examined the potential for endozoochoric dispersal of exotic plants by Callosciurus erythraeus introduced in the Pampas Region of Argentina. We identified and characterized entire and damaged seeds found in squirrel faeces and evaluated the germination capacity and viability of entire seeds in laboratory assays. We collected 120 samples of squirrel faeces that contained 883 pellets in seasonal surveys conducted between July 2011 and June 2012 at 3 study sites within the main invasion focus of C. erythraeus in Argentina. We found 226 entire seeds in 21% of the samples belonging to 4 species of exotic trees and shrubs. Germination in laboratory assays was recorded for Morus alba and Casuarina sp.; however, germination percentage and rate was higher for seeds obtained from the fruits than for seeds obtained from the faeces. The largest size of entire seeds found in the faeces was 4.2 × 4.0 mm, whereas the damaged seeds had at least 1 dimension ≥ 4.7 mm. Our results indicated that C. erythraeus can disperse viable seeds of at least 2 species of exotic trees. C. erythraeus predated seeds of other naturalized species in the region. The morphometric description suggested a restriction on the maximum size for the passage of entire seeds through the digestive tract of squirrels, which provides useful information to predict its role as a potential disperser or predator of other species in other invaded communities.

Bobadilla|S Yasmin|SY|
Benitez|Verónica V|VV|
Guichón|M Laura|ML|

Callosciurus erythraeus
Argentina
endozoochory
invasive species
mutualism


Principles of Fibrinogen Fiber Assembly In Vitro.

Abstract: Fibrinogen nanofibers hold great potential for applications in wound healing and personalized regenerative medicine due to their ability to mimic the native blood clot architecture. Although versatile strategies exist to induce fibrillogenesis of fibrinogen in vitro, little is known about the underlying mechanisms and the associated length scales. Therefore, in this manuscript the current state of research on fibrinogen fibrillogenesis in vitro is reviewed. For the first time, the manifold factors leading to the assembly of fibrinogen molecules into fibers are categorized considering three main groups: substrate interactions, denaturing and non-denaturing buffer conditions. Based on the meta-analysis in the review it is concluded that the assembly of fibrinogen is driven by several mechanisms across different length scales. In these processes, certain buffer conditions, in particular the presence of salts, play a predominant role during fibrinogen self-assembly compared to the surface chemistry of the substrate material. Yet, to tailor fibrous fibrinogen scaffolds with defined structure-function-relationships for future tissue engineering applications, it still needs to be understood which particular role each of these factors plays during fiber assembly. Therefore, the future combination of experimental and simulation studies is proposed to understand the intermolecular interactions of fibrinogen, which induce the assembly of soluble fibrinogen into solid fibers.

nanofibers
wound healing
self-assembly
blood coagulation
protein aggregation
tissue engineering scaffolds


The challenge of personalized cell biology: The example of microvillus inclusion disease.

Abstract: Whole exome sequencing now provides a tool for rapid analysis of patients manifesting congenital diseases. Congenital diarrheal diseases provide a critical example of the challenges of combining identification of genetic mutations responsible for disease with characterization of the cell biological and cell physiological deficits observed in patients. Recent studies exploring the cellular events associated with loss of functional Myosin 5B (MYO5B) have demonstrated the importance of cell biological and physiological analyses to provide a greater understanding of the implications of pathological mutations. Development of enteroids derived from biopsies of patients with complex congenital diarrheal diseases provides a critical resource for evaluation of the cell biological impact of specific monogenic mutations on enterocyte function. The ability to identify putative causative mutations for congenital disease now provides an opportunity to coordinate the efforts of physicians and cell biologists in an effort to provide patients with personalized cell biology analysis to improve patient diagnosis and treatment.

whole exome sequencing
MYO5B
enterocytes
DGAT1
diarrhea
epithelia
neonates


Investigation of toxic effects of imidazolium ionic liquids, [bmim][BF4] and [omim][BF4], on marine mussel Mytilus galloprovincialis with or without the presence of conventional solvents, such as acetone.

Abstract: This study investigated the cytotoxic, oxidative and genotoxic effects of two commonly used imidazolium ionic liquids (ILs), [bmim][BF4] (1-butyl-3-methylimidazolium) and [omim][BF4] (1-methyl-3-octylimidazolium tetrafluoroborate), on the marine mussel Mytilus galloprovincialis, as well as whether acetone could mediate their toxic profile. In this context, mussels were firstly exposed to different concentrations of [bmim][BF4] or [omim][BF4], with or without the presence of acetone (at a final concentration of 0.06% v/v), for a period of 96h, in order to determine the concentration that causes 50% mussel mortality (LC50 values) in each case. Thereafter, mussels were exposed to sub- and non-lethal concentrations of ILs for investigating their ability to cause lysosomal membrane impairment (with the use of neutral red retention assay/NRRT), superoxide anion and lipid peroxidation byproduct (malondialdehyde/MDA) formation, as well as DNA damage and formation of nuclear abnormalities in hemocytes. The results showed that [omim][BF4] was more toxic than [bmim][BF4] in all cases, while the presence of acetone resulted in a slight attenuation of its toxicity. The different toxic behavior of ILs was further revealed by the significantly lower levels of NRRT values observed in [omim][BF4]-treated mussels, compared to those occurring in [bmim][BF4] in all cases. Similarly, [bmim][BF4]-mediated oxidative and genotoxic effects were observed only in the highest concentration tested (10mgL(-1)), while [omim][BF4]-mediated effects were enhanced at lower concentrations (0.01-0.05mgL(-1)). Overall, the present study showed that [bmim][BF4] and [omim][BF4] could induce not only lethal but also nonlethal effects on mussel M. galloprovincialis. The extent of [bmim][BF4] and/or [omim][BF4]-mediated effects could be ascribed to the length of each IL alkyl chain, as well as to their lipophilicity. Moreover, the role of acetone on the obtained toxic effects of the specific ILs was reported for the first time, giving evidence for its interaction with the ILs and the modulation of their toxicity.

Mussels
Cytotoxicity
Genotoxicity
Oxidative stress
[bmim][BF(4)]
[omim][BF(4)]


Multiplicity of effects and health benefits of resveratrol.

Abstract: Resveratrol is mainly found in grapes and red wine, also in some plants and fruits, such as peanuts, cranberries, pistachios, blueberries and bilberries. Moreover, nowadays this compound is available as purified preparation and dietary supplement. Resveratrol provides a wide range of benefits, including cardiovascular protective, antiplatelet, antioxidant, anti-inflammatory, blood glucose-lowering and anticancer activities, hence it exhibits a complex mode of action. During the recent years, these properties have been widely studied in animal and human models, both in vitro and in vivo. This paper is intended to present information published during the recent years on the biological activities and multiple effects of resveratrol.

Kuršvietienė|Lolita|L| Stanevičienė|Inga|I| Mongirdienė|Aušra|A| Bernatonienė|Jurga|J|

Resveratrol Antioxidant Anticancer Radicals


Analysis of the impact of COVID-19 pandemic on house-staff in the USA: addressing the ripple effects.

Abstract: Background: The novel corona virus has changed the way individuals interact with each other and society. In the medical sector, this has affected the residents and fellows who spend the majority of their time on the front lines. Methods: We conducted a cross-sectional survey to assess the impact of the COVID-19 pandemic on the lives and training of house-staff across the USA. Respondents in our survey reported feeling significantly overwhelmed by the ongoing pandemic. Results: The majority of house-staff were significantly concerned about the lack of protective equipment, inability to safeguard themselves from infection and inability to look after their families. Concerns regarding contracting the infection and transmitting it to their loved ones were reported as a cause of mental distress among resident physicians. Increasing patient load, lack of protective equipment, and disruption of educational and academic activities during the COVID-19 pandemic have all reportedly affected the training and overall well-being of resident physicians. Conslusion: Our study adds further support for measures to safeguard house-staff with proper protective equipment and ensure adequate support for both mental and physical well-being during these challenging times.

COVID-19
pandemic
graduate medical education
physician burnout
resident wellness


Development of curcumin-loaded composite phospholipid ethosomes for enhanced skin permeability and vesicle stability.

Abstract: Ethosomes are widely applied as the carriers for the transdermal delivery of hydrophobic and hydrophilic drugs. Herein, curcumin-loaded ethosomes (CE) with different phospholipid composition were formulated and thoroughly compared. A significant interaction between the unsaturated phosphatidylcholine (PC) and saturated hydrogenated phosphatidylcholine (HPC) was found by molecular simulation and differential scanning calorimetry (DSC), which led to the reduction of PC peroxidation with the presence of HPC. Subsequently, the composite phospholipid ethosomes containing curcumin were prepared for the first time to evaluate their properties in comparison with the conventional ethosomes composed of PC (CE-P) or HPC (CE-H). CE with PC/HPC ratio of 1:1 (CE-P1H1) with the best vesicle stability and flexibility significantly decreased the uptake by HaCaT cells compared to CE-H and free curcumin, indicating reduced skin cell toxicity. Compared with free curcumin, CE-P1H1 had the highest transdermal efficiency (p < 0.001), followed by CE-P (p < 0.05), partly due to the fact that CE-P1H1 could disturb lipid domain of stratum corneum (SC). Moreover, CE-P1H1 was found to promote curcumin for deep penetration of the skin via the hair follicles route. Our study has shown that using composite phospholipid ethosomes as lipid vesicular carriers could enhance transdermal penetration of drugs and increase in the vesicle stability.

Li|Yu|Y| Xu|Fei|F| Li|Xiang|X| Chen|Si-Ying|SY| Huang|Lin-Yu|LY| Bian|Yao-Yao|YY| Wang|Jia|J| Shu|Ye-Ting|YT| Yan|Guo-Jun|GJ| Dong|Jie|J| Yin|Shao-Ping|SP| Gu|Wei|W| Chen|Jun|J|

Ethosomes
Transdermal
Phosphatidylcholine
Hydrogenated phosphatidylcholine
Curcumin


The impact of varying abiotic humification conditions and the resultant structural characteristics on the copper complexation ability of synthetic humic-like acids in aquatic environments.

Abstract: Humic acid (HA) has a high complexation ability with metal ions due to its functional groups. In this study, 11 synthetic humic-like acids (SHLAs) were prepared under varying abiotic humification conditions: precursor species (glycine-catechol and glycine-catechol-glucose), precursor concentrations (from 0.25 M:0.25 M to 1 M:1 M), pH (6-8), temperature (25-45 °C) and mass of MnO2 catalyst (1.3-2.5% w/v). The effect of the varying humification conditions on the complexation ability of the SHLA for Cu2+ were investigated together with the relationships between Cu complexation ability and the structure of the SHLAs (elemental composition, type and content of functional groups, AL/AR, E4/E6). Conditional stability constants (log K) of the SHLAs ranged from 6.00 to 6.42 and complexation capacities ranged from 1.76 mmol/g to 2.61 mmol/g. SHLAs synthesized at lower temperature (25 ℃), pH 8, low precursor concentrations (glycine:catechol= 0.25 M:0.25 M) and a larger proportion of catalyst (2.5% w/v) had a larger copper complexation ability. Log K values of SHLAs had significant positive correlations with carboxylic carbon (r = 0.671, p < 0.05), carboxylic group content (r = 0.890, p < 0.01) and O/C ratio (r = 0.618, p < 0.05), and significant negative correlations with aliphatic carbon (r = -0.616, p < 0.05), total C (r = -0.685, p < 0.05) and total H contents (r = -0.654, p < 0.05). Complexation capacities had a significant positive correlation with total N (r = 0.826, p < 0.01) and a significant negative correlation with C/N ratio (r = -0.823, p < 0.01).

D017550:Spectroscopy, Fourier Transform Infrared

Abiotic humification
Structural characteristics
Copper complexation ability
Synthetic humic-like acids
Metals


Molecular Recognition and Visual Detection of G-Quadruplexes by a Dicarbocyanine Dye.

Abstract: The interactions of a dicarbocyanine dye 3,3'-diethylthiadicarbocyanine, DiSC2(5), with DNA G-quadruplexes were studied by means of a combination of various spectroscopic techniques. Aggregation of excess dye as a result of its positive charge is promoted by the presence of the polyanionic quadruplex structure. Specific high-affinity binding to the parallel quadruplex of the MYC promoter sequence involves stacking of DiSC2(5) on the external G-tetrads; the 5'-terminal tetrad is the favored binding site. Significant energy transfer between DNA and the dye in the UV spectral region is observed upon DiSC2(5) binding. The transfer efficiency strongly depends on the DNA secondary structure as well as on the G-quadruplex topology. These photophysical features enable the selective detection of DNA quadruplexes through sensitized DiSC2(5) fluorescence in the visible region.

Karg|Beatrice|B| Funke|Andrea|A| Ficht|Anna|A| Sievers-Engler|Adrian|A| Lämmerhofer|Michael|M| Weisz|Klaus|K|

molecular recognition
G-quadruplexes
energy transfer
cyanines
dyes/pigments


Phase II study of concomitant radiotherapy with atezolizumab in oligometastatic soft tissue sarcomas: STEREOSARC trial protocol.

Abstract:
INTRODUCTION
Up to 50% of soft tissue sarcoma (STS) patients develop metastases in the course of their disease. Cytotoxic therapy is a standard treatment in this setting but yields average tumour response rates of 25% at first line and ≤10% at later lines. In oligometastatic stage, stereotactic body radiation therapy (SBRT) allows reaching high control rates at treated sites (≥80%) and is potentially equally effective to surgery in term of overall survival. In order to shift the balance towards antitumour immunity by multisite irradiation, radiation could be combined with inhibitors of the immunosuppressive pathways.

METHODS AND ANALYSIS
STEREOSARC is a prospective, multicentric, randomised phase II, designed to evaluate the efficacy of SBRT associated with immunotherapy versus SBRT only. Randomisation is performed with a 2:1 ratio within two arms. The primary objective is to evaluate the efficacy, in term of progression-free survival (PFS) rate at 6 months, of immunomodulated stereotactic multisite irradiation in oligometastatic sarcoma patients. The secondary objectives include PFS by immune response criteria, overall survival, quality-of-life evaluation and developing mathematical models of tumour growth and dissemination predictive of oligometastatic versus polymetastatic evolution. Patients will be randomised in two groups: SBRT with atezolizumab and SBRT alone. The total number of included patients should be 103.

TRIAL REGISTRATION
The trial is registered on ClinicalTrials.gov (ID: NCT03548428).

ETHICS AND DISSEMINATION
This study has been approved by Comité de Protection des Personnes du sud-ouest et outre-mer 4 on 18 October 2019 (Reference CPP2019-09-076-PP) and from National Agency for Medical and Health products Safety (Reference: MEDAECNAT-2019-08-00004_2017-004239-35) on 18 September 2019.The results will be disseminated to patients upon individual request or through media release from scientific meetings. The results will be communicated through scientific meetings and publications.

le Guevelou|Jennifer|J|
Debaigt|Colin|C|
Saada-Bouzid|Esma|E|
Viotti|Julien|J|
Khalladi|Nazim|N|
Thibouw|David|D|
Penel|Nicolas|N|
Sunyach|Marie Pierre|MP|
Moureau-Zabotto|Laurence|L|
Benchalal|Mohamed|M|
Veresezan|Ovidiu|O|
Ducassou|Anne|A|
le Pechoux|Cecile|C|
Jolnerovski|Maria|M|
Bazille|Celine|C|
Vaur|Dominique|D|
Escande|Alexandre|A|
Serre|Raphael|R|
Lovera|Christine|C|
Thariat|Juliette|J|0000-0001-7853-5468

D017322:Clinical Trials, Phase II as Topic

D016032:Randomized Controlled Trials as Topic

sarcomas
SBRT
immunotherapy
abscopal effect
tumor mutational burden


Tannic acid modulates fibroblast proliferation and differentiation in response to pro-fibrotic stimuli.

Abstract: In response to tissue injury, fibroblasts migrate into the wound, where they undergo proliferation and differentiation. The persistence of these differentiated fibroblasts (myofibroblasts) is associated with excessive scarring in various organs. We aimed to investigate the effects of Tannic acid (TA) on fibroblast proliferation and differentiation, and found that TA inhibited fibroblast differentiation as assessed by reduced expression of α-smooth muscle actin, N-cadherin, and type-1-collagen. TA also prevented the TGF-β1-induced alteration in the expression of two classes of genes involved in the remodeling of extracellular matrix (ECM) proteins, namely matrix metalloproteinases (Mmp-2 and -9) and tissue inhibitors of metalloproteinases (Timp-1 and -3). Further, TA suppressed TGF-β1-induced cell proliferation and induced cell cycle arrest at G0/G1 phase via targeting Cyclins expression. Finally, TA exerted its inhibitory effects by decreasing the phosphorylation of Smad and ERK signaling. In sum, our results suggesting that TA may be a potential therapeutic agent for pathological fibrosis.

D053773:Transforming Growth Factor beta1

tannic acid
myofibroblast
cell proliferation
fibrosis
TGF-β signaling
dietary component


Durable lesion formation while avoiding esophageal injury during ablation of atrial fibrillation: Lessons learned from late gadolinium MR imaging.

Abstract:
INTRODUCTION
Adequate catheter/atrial tissue contact is critical for lesion formation during radiofrequency (RF) ablation of atrial fibrillation (AF). Late gadolinium enhancement magnetic resonance imaging (LGE-MRI) is a unique tool for the evaluation of lesion formation and detection of acute esophageal injury.

METHODS
LGE-MRIs were obtained prior, within 24 hours of, and at 115 ± 62 days after first AF ablation in 36 patients. The Visitag module of CARTO3 was used to collect contact force (CF) and duration from a CF sensing ablation catheter for each registered ablation point. The minimum CF resulting in permanent lesions was determined. Esophageal enhancement detected by acute LGE-MRI was classified as mild, moderate, and severe. The CF resulting in esophageal enhancement was determined.

RESULTS
A total of 4,642 registered ablation tags at 50 W power were analyzed. The mean RF duration (5.9 ± 3.7 vs. 5.6 ± 3.2 seconds, P < 0.05), CF (11.5 ± 5.6 vs. 10.9 ± 5.4 g, P < 0.001), and force time integral (FTI) (67.3 ± 54.5 vs. 62.2 ± 52.7 gs, P < 0.01) were significantly higher between ablation tags with and without associated LGE-MRI detected scar. The mean CF (15.7 ± 6.1 vs. 12.6 ± 5.9 g, P < 0.05, n  =  17 patients) in areas of esophageal enhancement was greater than areas without.

CONCLUSION
Left atrial short duration ablation lesions with a CF greater than 12 g are more likely to be associated with permanent lesion formation. Ablating on top of the esophagus, CF less than 15 g would help minimize esophageal wall injury.

ablation
atrial fibrillation
LGE-MRI
atrial fibrosis
force sensing catheter


Breeding With Major and Minor Genes: Genomic Selection for Quantitative Disease Resistance.

Abstract: Disease resistance in plants is mostly quantitative, with both major and minor genes controlling resistance. This research aimed to optimize genomic selection (GS) models for use in breeding programs that are needed to select both major and minor genes for resistance. In this study, stripe rust (Puccinia striiformis Westend. f. sp. tritici Erikss.) of wheat (Triticum aestivum L.) was used as a model for quantitative disease resistance. The quantitative nature of stripe rust is usually phenotyped with two disease traits, infection type (IT) and disease severity (SEV). We compared two types of training populations composed of 2,630 breeding lines (BLs) phenotyped in single-plot trials from 4 years (2016-2020) and 475 diversity panel (DP) lines from 4 years (2013-2016), both across two locations. We also compared the accuracy of models using four different major gene markers and genome-wide association study (GWAS) markers as fixed effects. The prediction models used 31,975 markers that are replicated 50 times using a 5-fold cross-validation. We then compared GS models using a marker-assisted selection (MAS) to compare the prediction accuracy of the markers alone and in combination. GS models had higher accuracies than MAS and reached an accuracy of 0.72 for disease SEV. The major gene and GWAS markers had only a small to nil increase in the prediction accuracy more than the base GS model, with the highest accuracy increase of 0.03 for the major markers and 0.06 for the GWAS markers. There was a statistical increase in the accuracy using the disease SEV trait, BLs, population type, and combining years. There was also a statistical increase in the accuracy using the major markers in the validation sets as the mean accuracy decreased. The inclusion of fixed effects in low prediction scenarios increased the accuracy up to 0.06 for GS models using significant GWAS markers. Our results indicate that GS can accurately predict quantitative disease resistance in the presence of major and minor genes.

Merrick|Lance F|LF|
Burke|Adrienne B|AB|
Chen|Xianming|X|
Carter|Arron H|AH|

genomic selection
disease resistance
stripe rust
genome-wide associate studies
fixed-effect
rrBLUP


An Integrated Analysis of Neural Network Correlates of Categorical and Dimensional Models of Attention-Deficit/Hyperactivity Disorder.

Abstract:
BACKGROUND
Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder, putatively induced by dissociable dysfunctional biobehavioral pathways. Here, we present a proof-of-concept study to parse ADHD-related heterogeneity in its underlying neurobiology by investigating functional connectivity across multiple brain networks to 1) disentangle categorical diagnosis-related effects from dimensional behavior-related effects and 2) functionally map these neural correlates to neurocognitive measures.

METHODS
We identified functional connectivity abnormalities related to ADHD across 14 networks within a large resting-state functional magnetic resonance imaging dataset (n = 409; age = 17.5 ± 3.3 years). We tested these abnormalities for their association with the categorical ADHD diagnosis and with dimensional inattention and hyperactivity/impulsivity scores using a novel modeling framework, creating orthogonalized models. Next, we evaluated the relationship of these findings with neurocognitive measures (working memory, response inhibition, reaction time variability, reward sensitivity).

RESULTS
Within the default mode network, we mainly observed categorical ADHD-related functional connectivity abnormalities, unrelated to neurocognitive measures. Clusters within the visual networks primarily related to dimensional scores of inattention and reaction time variability, while findings within the sensorimotor networks were mainly linked to hyperactivity/impulsivity and both reward sensitivity and working memory. Findings within the cerebellum network and salience network related to both categorical and dimensional ADHD measures and were linked to response inhibition and reaction time variability.

CONCLUSIONS
This proof-of-concept study identified ADHD-related neural correlates across multiple functional networks, showing distinct categorical and dimensional mechanisms and their links to neurocognitive functioning.

Pruim|Raimon H R|RHR|
Beckmann|Christian F|CF|
Oldehinkel|Marianne|M|
Oosterlaan|Jaap|J|
Heslenfeld|Dirk|D|
Hartman|Catharina A|CA|
Hoekstra|Pieter J|PJ|
Faraone|Stephen V|SV|
Franke|Barbara|B|
Buitelaar|Jan K|JK|
Mennes|Maarten|M|

D001289:Attention Deficit Disorder with Hyperactivity

Resting-state functional magnetic resonance imaging


Whisking Kinematics Enables Object Localization in Head-Centered Coordinates Based on Tactile Information from a Single Vibrissa.

Abstract: During active tactile exploration with their whiskers (vibrissae), rodents can rapidly orient to an object even though there are very few proprioceptors in the whisker muscles. Thus a long-standing question in the study of the vibrissal system is how the rat can localize an object in head-centered coordinates without muscle-based proprioception. We used a three-dimensional model of whisker bending to simulate whisking motions against a peg to investigate the possibility that the 3D mechanics of contact from a single whisker are sufficient for localization in head-centered coordinates. Results show that for nearly all whiskers in the array, purely tactile signals at the whisker base - as would be measured by mechanoreceptors, in whisker-centered coordinates - could be used to determine the location of a vertical peg in head-centered coordinates. Both the "roll" and the "elevation" components of whisking kinematics contribute to the uniqueness and resolution of the localization. These results offer an explanation for a behavioral study showing that rats can more accurately determine the horizontal angle of an object if one column, rather than one row, of whiskers is spared.

Yang|Anne E T|AE|
Hartmann|Mitra J Z|MJ|

whisker
orienting
biomechanics
superior colliculus
touch
trigeminal


Identification and characterization of an Egr ortholog as a neural immediate early gene in the European honeybee (Apis mellifera L.).

Abstract: To date, there are only few reports of immediate early genes (IEGs) available in insects. Aiming at identifying a conserved IEG in insects, we characterized an Egr homolog of the honeybee (AmEgr: Apis mellifera Egr). AmEgr was transiently induced in whole worker brains after seizure induction. In situ hybridization for AmEgr indicated that neural activity of a certain mushroom body (a higher brain center) neuron subtype, which is the same as that we previously identified using another non-coding IEG, termed kakusei, is more enhanced in forager brains. These findings suggest that Egr can be utilized as an IEG in insects.

D000818:Animals
D001483:Base Sequence
D001516:Bees
D017931:DNA Primers
D051766:Early Growth Response Protein 1
D005247:Feeding Behavior
D017781:Genes, Immediate-Early
D024521:Mushroom Bodies

Immediate early gene
Honeybee
Egr-family


Anaplastic Features in Advanced Prostate Cancer With and Without DNA Damage Repair Mutations.

Abstract:
BACKGROUND
Anaplastic prostate cancer has a poor prognosis with limited treatment options. Seven clinical features of anaplastic prostate cancer have been prospectively identified. In this phase II clinical trial, we identified mutations, including DNA damage repair (DDR) mutations, in patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated with durvalumab and olaparib and determined how many of them can be described as anaplastic, and we examined the overlap between anaplastic features and DDR mutations.

METHODS
Eligible patients with mCRPC received prior enzalutamide, abiraterone, or both. Patients were treated with durvalumab 1500 mg i.v. every 28 days and olaparib 300 mg p.o. every 12 hours until disease progression or unacceptable toxicity. Patients underwent mandatory baseline biopsies of metastatic lesions.

RESULTS
Baseline characteristics were similar between anaplastic and nonanaplastic patients. Eleven patients (20%) displayed clear anaplastic features, and 43 (78.2%) lacked anaplastic features. In the anaplastic group, 2/11 (18.2%) had germline DRR mutations, and 4/11 (36.3%) had somatic DDR mutations. In the nonanaplastic group, 7/43 (16.3%) had germline mutations, and 13/43 (30.2%) had somatic mutations. Median progression-free survival (PFS) times in patients with anaplastic features (6.5 months) and without anaplastic features (5.1 months) were similar (hazard ratio 0.998, P = .996).

CONCLUSIONS
Patients with and without anaplastic features appear to have similar total rates of DDR mutations and also similar rates of somatic and germline DDR mutations. Patients with anaplastic features have a trend toward improved PFS when treated with olaparib and durvalumab compared with nonanaplastic patients.

Chau|Vincent|V|
Madan|Ravi A|RA|
Bilusic|Marijo|M|
Owens|Helen|H|
Cordes|Lisa M|LM|
Marte|Jennifer L|JL|
Gulley|James L|JL|
Lee|Jung-Min|JM|
Dahut|William L|WL|
Karzai|Fatima|F|

Anaplastic
mCRPC
durvalumab
olaparib
DDR mutations
enzalutamide
abiraterone
immunotherapy


Truly sedentary? The multi-range tactic as a response to resource heterogeneity and unpredictability in a large herbivore.

Abstract: Much research on large herbivore movement has focused on the annual scale to distinguish between resident and migratory tactics, commonly assuming that individuals are sedentary at the within-season scale. However, apparently sedentary animals may occupy a number of sub-seasonal functional home ranges (sfHR), particularly when the environment is spatially heterogeneous and/or temporally unpredictable. The roe deer (Capreolus capreolus) experiences sharply contrasting environmental conditions due to its widespread distribution, but appears markedly sedentary over much of its range. Using GPS monitoring from 15 populations across Europe, we evaluated the propensity of this large herbivore to be truly sedentary at the seasonal scale in relation to variation in environmental conditions. We studied movement using net square displacement to identify the possible use of sfHR. We expected that roe deer should be less sedentary within seasons in heterogeneous and unpredictable environments, while migratory individuals should be seasonally more sedentary than residents. Our analyses revealed that, across the 15 populations, all individuals adopted a multi-range tactic, occupying between two and nine sfHR during a given season. In addition, we showed that (i) the number of sfHR was only marginally influenced by variation in resource distribution, but decreased with increasing sfHR size; and (ii) the distance between sfHR increased with increasing heterogeneity and predictability in resource distribution, as well as with increasing sfHR size. We suggest that the multi-range tactic is likely widespread among large herbivores, allowing animals to track spatio-temporal variation in resource distribution and, thereby, to cope with changes in their local environment.

Couriot|Ophélie|O|0000-0002-4547-0079
Hewison|A J Mark|AJM|
Saïd|Sonia|S|
Cagnacci|Francesca|F|
Chamaillé-Jammes|Simon|S|
Linnell|John D C|JDC|
Mysterud|Atle|A|
Peters|Wibke|W|
Urbano|Ferdinando|F|
Heurich|Marco|M|
Kjellander|Petter|P|
Nicoloso|Sandro|S|
Berger|Anne|A|
Sustr|Pavel|P|
Kroeschel|Max|M|
Soennichsen|Leif|L|
Sandfort|Robin|R|
Gehr|Benedikt|B|
Morellet|Nicolas|N|

Residency
Sub-seasonal functional home range
Roe deer
Migration
Plasticity


Evaluation of radiofrequency safety by high temperature resolution MR thermometry using a paramagnetic lanthanide complex.

Abstract:
PURPOSE
The current practice of calculating the specific absorption rate (SAR) relies on local temperature measurements made using temperature probes. For an accurate SAR measurement, a temperature imaging method that provides high temperature sensitivity is desirable, because acceptable levels of SAR produce small temperature changes. MR thermometry using paramagnetic lanthanide complexes can be used to obtain absolute temperature measurements with sub-degree temperature and sub-millimeter spatial resolution. The aim of this study was to develop and evaluate a high temperature resolution MR technique to determine SAR.

METHODS
MR thermometry using a paramagnetic lanthanide complex thulium 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis (methylene phosphonate) (TmDOTP(5-)), which has an almost 10(2) times stronger chemical shift temperature dependence than water, was used to develop a novel method for SAR measurement. Three-dimensional temperature and SAR images were calculated using MR images acquired with a conventional gradient recalled echo sequence and SAR-intensive T1ρ sequence. Effects of the presence of conducting wire and increasing T1ρ spin-lock pulse duration were also examined.

RESULTS
SAR distribution could be visualized clearly and surges associated with conducting wires and increasing pulse duration were identified clearly in the computed high spatial resolution SAR images.

CONCLUSION
A novel method with high temperature sensitivity is proposed as a tool to evaluate radiofrequency safety in MRI.

MR thermometry
paramagnetic lanthanide complex
specific absorption rate (SAR)
RF heating


Retirement, age, gender and mental health: findings from the 45 and Up Study.

Abstract:
OBJECTIVES
To examine the relationships of retirement and reasons for retirement with psychological distress in men and women at the age of 45-79 years.

METHOD
Data from 202,584 Australians participating in the large-scale 45 and Up Study was used. Psychological distress was measured by the Kessler psychological distress scale. Associations between different work status and reasons for retirement with psychological distress were assessed for men and women at different ages using logistic regression.

RESULTS
Being fully retired or unemployed was associated with the high levels of psychological distress compared to being in paid work for men and women aged 45-64 (p < 0.0001), and for men aged 65-74 years (p ≤ 0.0014). At the age of 75-79 years, there was no difference in psychological distress between different work statuses. Among retirees, retirement due to ill health, being made redundant or caring duty was associated with the high level of psychological distress.

CONCLUSION
The association between work and mental health underscores the importance of policies and strategies to encourage and enable people to continue in the workforce after age 55, particularly for men. Important reasons for retirement with worse mental health outcomes include redundancy, ill health and needing to care for family or a friend. These circumstances will affect whether a person can continue working and their risk of poor mental health, and both considerations should be addressed in developing approaches for maintaining older workers or assisting them with their retirement transition.

Vo|Kha|K|
Forder|Peta M|PM|
Tavener|Meredith|M|
Rodgers|Bryan|B|
Banks|Emily|E|
Bauman|Adrian|A|
Byles|Julie E|JE|

retirement
age
gender
mental health
reasons for retirement


Investigating the association between anxiety symptoms and mood disorder in high-risk offspring of bipolar parents: a comparison of Joint and Cox models.

Abstract:
BACKGROUND
Anxiety is associated with mood disorders including bipolar disorder. Two statistical modelling frameworks were compared to investigate the longitudinal relationship between repeatedly measured anxiety symptoms and the onset of depression and bipolar disorder in youth at confirmed familial risk.

METHODS
Prospectively collected data on 156 offspring of a parent with confirmed bipolar disorder participating in the Canadian Flourish high-risk offspring longitudinal cohort study were used for this analysis. As part of the research protocol at approximately yearly visits, a research psychiatrist completed the HAM-A and a semi-structured diagnostic research interview following KSADS-PL format. Diagnoses using DSM-IV criteria were made on blind consensus review of all available clinical information. We investigated two statistical approaches, Cox model and Joint model, to evaluate the relationship between repeated HAM-A scores and the onset of major depressive or bipolar disorder. The Joint model estimates the trajectory of the longitudinal variable using a longitudinal sub-model and incorporates this estimated trajectory into a Cox sub-model.

RESULTS
There was evidence of an increased hazard of major mood disorder for high-risk individuals with higher HAM-A scores under both modelling frameworks. After adjusting for other covariates, a one-unit increase in log-transformed HAM-A score was associated with a hazard ratio of 1.74 (95% CI (1.12, 2.72)) in the Cox model compared to 2.91(95% CI (1.29, 6.52)) in the Joint model. In an exploratory analysis there was no evidence that family clustering substantially affected the conclusions.

CONCLUSIONS
Estimated effects from the conventional Cox model, which is often the model of choice, were dramatically lower in this dataset, compared to the Joint model. While the Cox model is often considered the approach of choice for analysis, research has shown that the Joint model may be more efficient and less biased. Our analysis based on a Joint model suggests that the magnitude of association between anxiety and mood disorder in individuals at familial risk of developing bipolar disorder may be stronger than previously reported.

Anxiety
High-risk
Offspring
Cox model
Bipolar disorder
Longitudinal
Joint model
Depressive disorder
Measurement error
Survival analysis


A specific and biocompatible fluorescent sensor based on the hybrid of GFP chromophore and peptide for HSA detection.

Abstract: It is still a challenge for clinical diagnostics to design non-toxic and selective sensors for a specific analyte in blood serum, which contains a large number of proteins, small molecules, and ions. Herein, H1, a synthetic hybrid of green fluorescent protein (GFP) chromophore and peptide for human serum albumin (HSA) detection via obvious fluorescence enhancement was reported. The fluorescence response was caused by the non-covalent binding between H1 and the subdomain IIA cavity of HSA, and this specific binding behavior can be confirmed by the decrease of fluorescence intensity of the sole tryptophan residue (Trp-214) located in the same subdomain. H1 showed remarkable sensitivity and selectivity toward HSA without interference from other proteins. A good linear relationship between the fluorescence intensity of H1 and HSA concentration from 0 to 67.0μgmL(-1) was obtained with the detection limit reaching as low as 198.6ngL(-1). Moreover, H1 was successfully utilized to detect trace HSA in healthy human urine (HU) and human blood serum (HBS), respectively. The resulting H1/HSA system also showed a satisfactory sensing ability toward anionic surfactant sodium dodecyl sulfate (SDS) through decreased fluorescence intensity with the detection limit of 3.48ngL(-1).

Liao|Caiyun|C| Li|Fangfang|F| Huang|Shanshan|S| Zheng|Baozhan|B| Du|Juan|J| Xiao|Dan|D|

GFP chromophore
HSA
SDS
BSA
Fluorescence detection


A simulations approach for meta-analysis of genetic association studies based on additive genetic model.

Abstract: Meta-analysis of genetic association studies is being increasingly used to assess phenotypic differences between genotype groups. When the underlying genetic model is assumed to be dominant or recessive, assessing the phenotype differences based on summary statistics, reported for individual studies in a meta-analysis, is a valid strategy. However, when the genetic model is additive, a similar strategy based on summary statistics will lead to biased results. This fact about the additive model is one of the things that we establish in this paper, using simulations. The main goal of this paper is to present an alternate strategy for the additive model based on simulating data for the individual studies. We show that the alternate strategy is far superior to the strategy based on summary statistics.

John|Majnu|M|
Lencz|Todd|T|
Malhotra|Anil K|AK|
Correll|Christoph U|CU|
Zhang|Jian-Ping|JP|

simulations
genetic association studies
summary statistics
additive model
2 × 2 table
GWAS
meta analysis
odds ratio


Sensing Peroxynitrite in Different Organelles of Murine RAW264.7 Macrophages With Coumarin-Based Fluorescent Probes.

Abstract: The elucidation of biological processes involving reactive oxygen species (ROS) facilitates a better understanding of the underlying progression of non-communicable diseases. Fluorescent probes are a powerful tool to study various ROS and have the potential to become essential diagnostic tools. We have developed a series of coumarin fluorescent probes for the selective and sensitive detection of peroxynitrite (ONOO-), a key ROS. Coumarin based probes exhibit good photostability, large Stokes shift and high quantum yields. The three ratiometric probes all contain a boronate ester motif for the detection of ONOO- and a distinctive organelle targeting group. The study of ONOO- generation in a particular organelle will allow more precise disease profiling. Hence, targeting groups for the mitochondria, lysosome and endoplasmic reticulum were introduced into a coumarin scaffold. The three ratiometric probes displayed sensitive and selective detection of ONOO- over other ROS species. All three coumarin probes were evaluated in murine RAW264.7 macrophages for detection of basal and stimulated ONOO- formation.

Weber|Maria|M|
Yamada|Namiko|N|
Tian|Xue|X|
Bull|Steven D|SD|
Minoshima|Masafumi|M|
Kikuchi|Kazuya|K|
Mackenzie|Amanda B|AB|
James|Tony D|TD|

peroxynitrite
fluorescence
reactive oxygen species
inflammation
molecular probe


Bilateral Plexiform Neurofibromas of the Posterior Interosseous Nerve Mimicking Dorsal Wrist Ganglions.

Abstract: A 33-year-old woman presented with bilateral dorsal wrist masses associated with pain and limited range of motion. On initial presentation, the masses were believed to be ganglion cysts and the patient opted for observation. Three years later, she was found to have a chest wall mass diagnosed by biopsy to be a neurofibroma. When she later returned to seek treatment for her wrist masses, magnetic resonance imaging demonstrated posterior interosseous nerve (PIN) neurofibromas. Dorsal wrist masses situated over the scapholunate interval are commonly attributed to ganglion cysts. Neurofibromas of the PIN, although rare, should be considered in the differential diagnosis when a mass elicits pain with percussion, fails to transilluminate, fails aspiration, or if the patient has a history of neurofibromas elsewhere in the body.

Gandhi|Rikesh A|RA|
Bozentka|David J|DJ|

neurofibroma
posterior interosseous nerve
Dorsal wrist mass
intraneural


Carriage of Staphylococcus species in the veterinary visiting dog population in mainland UK: molecular characterisation of resistance and virulence.

Abstract: This study investigated the prevalence of nasal carriage of staphylococci in dogs and determined the characteristics of the isolates. A total of 724 dogs from 87 veterinary practices across the mainland UK were screened for carriage of Staphylococcus spp. All isolates were examined for meticillin resistance (MR) and the presence of the mecA gene investigated in those isolates showing resistance. All coagulase-positive staphylococci and MR coagulase-negative staphylococci (MRCoNS) were subjected to antimicrobial susceptibility testing. Spa typing and DNA microarray analysis of resistance and virulence genes was carried out on all MR S. aureus (MRSA) and a subset of meticillin susceptible S. aureus (MSSA). Staphylococci were isolated from 399 (55.1%) of the dogs; only seven (1%) carried MRSA, all of which were identified as the dominant UK healthcare-associated strain (EMRSA-15, ST22). MSSA was identified in 47 (6.5%) dogs, the sequence types of which have been suggested as precursors to successful MRSA clones. Forty (5.5%) dogs carried MRCoNS, while no dogs carried MR S. pseudintermedius, although this is increasingly reported in mainland Europe. Resistance to antimicrobials among the isolates varied between species, with multidrug resistance (MDR) in 87.5% of MRCoNS and 21.8% of coagulase positive staphylococci. Microarray analysis of MRSA and a subset of MSSA isolates identified numerous virulence genes associated with pathogenesis, which are commonly identified in isolates of human origin. However, no isolates carried Panton-Valentine leukocidin (PVL) genes. This study suggests that MRSA carriage is low in the vet visiting dog population, but there is a diverse range of virulence and resistance determinants in canine S. aureus and MRCoNS isolates.

Wedley|Amy L|AL|
Dawson|Susan|S|
Maddox|Thomas W|TW|
Coyne|Karen P|KP|
Pinchbeck|Gina L|GL|
Clegg|Peter|P|
Jamrozy|Dorota|D|
Fielder|Mark D|MD|
Donovan|David|D|
Nuttall|Tim|T|
Williams|Nicola J|NJ|

D000818:Animals
D000900:Anti-Bacterial Agents
D000942:Antigens, Bacterial
D001426:Bacterial Proteins
D002353:Carrier State
D004283:Dog Diseases
D004285:Dogs
D018432:Drug Resistance, Multiple
D016106:Methicillin Resistance
D008826:Microbial Sensitivity Tests
D009666:Nose
D046915:Penicillin-Binding Proteins
D013203:Staphylococcal Infections
D013210:Staphylococcus
D013211:Staphylococcus aureus
D006113:United Kingdom
D014730:Veterinary Medicine
D037521:Virulence Factors

Staphylococcus
Dog
Prevalence
Microarray
MRSA
Antimicrobial resistance
Companion animals


Tumor-Targeted Delivery of the p53-Activating Peptide VIP116 with PEG-Stabilized Lipodisks.

Abstract: Stapled peptides targeting the interaction between p53 and its negative regulators MDM2 and MDM4 have exhibited great potential as anti-cancer drugs, albeit with room for improvement in formulation and tumor specificity. Lipid bilayer disks (lipodisks) have emerged as promising drug nanocarriers and can by attachment of targeting moieties be directed selectively towards tumor cells. Tumor-targeted delivery of stapled peptides by use of lipodisks may therefore increase the uptake in the tumors and limit toxicity in healthy tissue. Here, we utilized epidermal growth factor receptor (EGFR)-targeted lipodisks to deliver p53-activating stapled peptide VIP116 to EGFR-expressing tumor cells. We demonstrate that VIP116 can be stably formulated in lipodisks (maximum peptide/lipid molar ratio 0.11). In vitro cell studies verify specific binding of EGF-decorated lipodisks to tumor cells and confirm that targeted delivery of VIP116 significantly decreases tumor cell viability.

lipodisks
stapled peptides
p53
Lipid bilayer disks
nanocarriers
targeted drug delivery
targeted tumor therapy


High preoperative serum globulin in rectal cancer treated with neoadjunctive chemoradiation therapy is a risk factor for poor outcome.

Abstract: An elevated serum albumin (ALB) and albumin/globulin ratio (AGR) has been reported to be associated with a favorable prognosis for certain malignancies; however, little is known about the prognostic significance of globulin (GLB) in rectal cancer treated with neoadjuvant chemoradiation therapy (NCRT). The purpose of this study was to evaluate whether GLB analysis could predict the prognosis of patients received NCRT. A retrospective cohort of 293 locally advanced rectal cancer patients receiving NCRT followed by radical surgery was recruited between January 2006 and December 2012 at Fudan University Shanghai Cancer Center. Levels for preoperative GLB and ALB were obtained and used to calculate the AGR. Survival analysis was used to evaluate the predictive value of GLB. X-tile program determined 28.50, 36.20 and 1.20 as optimal cut-off value for GLB, ALB and AGR in terms of survival. Univariate and multivariate analysis revealed that low GLB levels were significantly associated with favorable rectal cancer-specific survival (RCSS) (P < 0.05). Conversely, low ALB levels were associated with a significantly worse RCSS (P = 0.010). Collectively, high preoperative GLB level was a significantly unfavorable factor for rectal cancer patients treated with NCRT. This easily obtained variable may serve as a valuable marker to predict the outcomes of such patient population.

Li|Qingguo|Q| Meng|Xianke|X| Liang|Lei|L| Xu|Ye|Y| Cai|Guoxiang|G| Cai|Sanjun|S|

globulin
Rectal cancer
albumin
survival analysis
neoadjuvant chemoradiotherapy therapy


Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system.

Abstract:
BACKGROUND
The preparation of human neurons derived from human induced pluripotent stem (iPS) cells can serve as a potential tool for evaluating the physiological and pathophysiological properties of human neurons and for drug development.

METHODS
In the present study, the functional activity in neuronal cells differentiated from human iPS cells was observed.

RESULTS
The differentiated cells expressed mRNAs for classical neuronal markers (microtubule-associated protein 2, β-tubulin III, calbindin 1, synaptophysin and postsynaptic density protein 95) and for subunits of various excitatory and inhibitory transmitters (NR1, NR2A, NR2B, GABAA α1). Moreover, the differentiated cells expressed neuropeptides and receptors which are predominantly present in the hypothalamus. The expression of mRNA for preopiomelanocortin, agouti-related protein (AgRP), melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) increased in culture with a peak on Day 30 which subsequently decreased at Day 45. Immunoreactivities for MC3R and MC4R were also observed in cells differentiated from human iPS cells. Application of a potent agonist for MC3R and MC4R, [Nle4, D-Phe7]-α-melanocyte-stimulating hormone, significantly increased intracellular cAMP levels, but this was suppressed by AgRP (83-132) and SHU9119.

CONCLUSIONS
These findings offer the possibility for drug developments using neurons differentiated from normal or disease-associated human iPS cells.

Yamada-Goto|Nobuko|N|
Ochi|Yukari|Y|
Katsuura|Goro|G|
Yamashita|Yui|Y|
Ebihara|Ken|K|
Noguchi|Michio|M|
Fujikura|Junji|J|
Taura|Daisuke|D|
Sone|Masakatsu|M|
Hosoda|Kiminori|K|
Gottschall|Paul E|PE|
Nakao|Kazuwa|K|

Neuronal cells
Melanocortin system
Human iPS cells
Neuropeptides
cAMP
Food intake


Impact of COVID-19 pandemic on rare diseases - A case study on thalassaemia patients in Bangladesh.

Abstract:
Objectives
Thalassaemia is a life-threatening rare disease, which requires regular blood transfusion and medical care. The information on how thalassaemia patients are affected during the unprecedented COVID-19 crisis is scarce. This study aimed to assess the impact of the COVID-19 pandemic on the blood transfusion and healthcare access of thalassaemia patients at the community level in Bangladesh.

Methods
A cross-sectional study was conducted among thalassaemia patients registered in a community-based 'thalassaemia registry' in Jamapur, Bangladesh.

Results
As compared to pre-COVID-19 time, the number of blood transfusions among patients under the thalassaemia registry was significantly reduced during COVID-19 pandemic (190 units versus 81 units). In addition, the median number of red cell transfusions per patient was dropped significantly from 4 units to one unit. Over 80% of patient had no access to healthcare services at all during the early phase of the pandemic.

Conclusions
Emergency response with appropriate mitigative measures must be a priority for addressing an acute shortage of blood supply in situations like COVID-19 pandemic.

Hossain|Mohammad Sorowar|MS|
Runa|Farhana|F|
Al Mosabbir|Abdullah|A|

COVID-19
Pandemic
Bangladesh
Blood transfusion
Beta-thalassemia
Thalassemia


Pharmacokinetics and Biodistribution of Eriocitrin in Rats.

Abstract: Eriocitrin plays a role in the reduction of oxidative stress and inflammation linked to the development of diabetes mellitus and atherosclerosis. We investigated the pharmacokinetics and distribution of eriocitrin metabolites in rats orally administered with eriocitrin. Plasma, urine, and organs were collected at 12 different time points from 0 to 24 h and analyzed by HPLC-PDA-MS. For the first time, the metabolism and distribution of orally administered eriocitrin were shown. Nine metabolites of eriocitrin were identified in rat urine, and seven in various tissues (eriodictyol, homoeriodictyol, hesperetin, and glucuronidated metabolites), and preliminary identifications of these metabolites are suggested. Overall, eriocitrin metabolites were widely distributed in the rat tissues, where homoeriodictyol and homoeriodictyol-7-O-glucuronide were the major metabolites. The half-lives of the metabolites in plasma were between 3 and 3.2 h, and the total bioavailability of eriocitrin was less than 1%.

D002851:Chromatography, High Pressure Liquid

pharmacokinetics biodistribution eriocitrin metabolites identification


Melatonin improves vascular cognitive impairment induced by ischemic stroke by remyelination via activation of ERK1/2 signaling and restoration of glutamatergic synapses in the gerbil hippocampus.

Abstract: Vascular dementia affects cognition by damaging axons and myelin. Melatonin is pharmacologically associated with various neurological disorders. In this study, effects of melatonin on cognitive impairment and related mechanisms were investigated in an animal model of ischemic vascular dementia (IVD). Melatonin was intraperitoneally administered to adult gerbils after transient global cerebral ischemia (tGCI) for 25 days beginning 5 days after tGCI. Cognitive impairment was examined using a passive avoidance test and the Barnes maze test. To investigate mechanisms of restorative effects by melatonin, neuronal damage/death, myelin basic protein (MBP, a marker for myelin), Rip (a marker for oligodendrocyte), extracellular signal-regulated protein kinase1/2 (ERK1/2) and phospho-ERK1/2 (p-ERK1/2), and vesicular glutamate transporter (VGLUT)-1 (a glutamatergic synaptic marker) in the hippocampal Cornu Ammonis 1 area (CA1) were evaluated using immunohistochemistry. Melatonin treatment significantly improved tGCI-induced cognitive impairment. Death of CA1 pyramidal neurons after tGCI was not affected by melatonin treatment. However, melatonin treatment significantly increased MBP immunoreactivity and numbers of Rip-immunoreactive oligodendrocytes in the ischemic CA1. In addition, melatonin treatment significantly increased ERK1/2 and p-ERK1/2 immunoreactivities in oligodendrocytes in the ischemic CA1. Furthermore, melatonin treatment significantly increased VGLUT-1 immunoreactive structures in the ischemic CA1. These results indicate that long-term melatonin treatment after tGCI improves cognitive deficit via restoration of myelin, increase of oligodendrocytes which is closely related to the activation of ERK1/2 signaling, and increase of glutamatergic synapses in the ischemic brain area.

Chen|Bai Hui|BH|
Park|Joon Ha|JH|
Lee|Yun Lyul|YL|
Kang|Il Jun|IJ|
Kim|Dae Won|DW|
Hwang|In Koo|IK|
Lee|Choong-Hyun|CH|
Yan|Bing Chun|BC|
Kim|Young-Myeong|YM|
Lee|Tae-Kyeong|TK|
Lee|Jae Chul|JC|
Won|Moo-Ho|MH|
Ahn|Ji Hyeon|JH|

Melatonin
ERK1/2
Glutamatergic synapse
Vascular dementia
Myelin
Oligodendrocyte


Challenging cases: thoracoscopic lobectomy with chest wall resection and sleeve lobectomy-Duke experience.

Abstract: Video-assisted thoracoscopic surgery (VATS) had recent advances in both equipment and technique so has been applied to more complex conditions in some thoracic surgery centers. We have adopted our VATS lobectomy experience for patients with chest wall invasion and endobronchial localized tumor requiring bronchial sleeve resection. We are describing our decision-making and surgical methods for these patients which we believe will be decreasing the number of contraindications for VATS and offering this surgical method for more patients.

Kara|H Volkan|HV|
Balderson|Stafford S|SS|
D'Amico|Thomas A|TA|

video-assisted thoracoscopic surgery (VATS)


An ortholog of CURLY LEAF/ENHANCER OF ZESTE like-1 is required for proper flowering in Brachypodium distachyon.

Abstract: Many plants require prolonged exposure to cold to acquire the competence to flower. The process by which cold exposure results in competence is known as vernalization. In Arabidopsis thaliana, vernalization leads to the stable repression of the floral repressor FLOWERING LOCUS C via chromatin modification, including an increase of trimethylation on lysine 27 of histone H3 (H3K27me3) by Polycomb Repressive Complex 2 (PRC2). Vernalization in pooids is associated with the stable induction of a floral promoter, VERNALIZATION 1 (VRN1). From a screen for mutants with a reduced vernalization requirement in the model grass Brachypodium distachyon, we identified two recessive alleles of ENHANCER OF ZESTE-LIKE 1 (EZL1). EZL1 is orthologous to A. thaliana CURLY LEAF 1, a gene that encodes the catalytic subunit of PRC2. B. distachyon ezl1 mutants flower rapidly without vernalization in long-day (LD) photoperiods; thus, EZL1 is required for the proper maintenance of the vegetative state prior to vernalization. Transcriptomic studies in ezl1 revealed mis-regulation of thousands of genes, including ectopic expression of several floral homeotic genes in leaves. Loss of EZL1 results in the global reduction of H3K27me3 and H3K27me2, consistent with this gene making a major contribution to PRC2 activity in B. distachyon. Furthermore, in ezl1 mutants, the flowering genes VRN1 and AGAMOUS (AG) are ectopically expressed and have reduced H3K27me3. Artificial microRNA knock-down of either VRN1 or AG in ezl1-1 mutants partially restores wild-type flowering behavior in non-vernalized plants, suggesting that ectopic expression in ezl1 mutants may contribute to the rapid-flowering phenotype.

D018506:Gene Expression Regulation, Plant

flowering
Brachypodium
vernalization
polycomb repressive complex
grasses
histone methlyation


Short-term Follow-up of Antibiotic-loaded Articulating Cement Spacers in Two-stage Revision of Infected Total Knee Arthroplasty: A Case Series.

Abstract:
OBJECTIVE
Infection of total knee arthroplasty (TKA) is a rare but devastating complication. Two-stage revision is an effective treatment for late infected TKA. This study aimed to assess the short-term results of two-stage revision using articulating antibiotic-loaded spacers.

METHODS
Twenty-five patients (10 men and 15 women) were diagnosed with late infections after TKA and treated with two-stage revision from April 2006 to August 2010; 19 of these patients had TKA for osteoarthritis and 6 for rheumatoid arthritis. Median age was 64.9 (range, 56-83) years. In the first-stage surgery, the prosthesis and all bone cement was removed. After thorough debridement, bone cement with vancomycin and tobramycin was put into a die cavity and made into temporary femoral and tibial spacers, respectively. In the cases of good knee range of motion, the temporary spacers were affixed to the bone surface using the same antibiotic bone cement. In the second surgery, gentamycin Refobacin Bone Cement with vancomycin was used to fix the prosthesis. After two-stage revision, patients were followed up clinically and radiologically at 1, 3, and 6 months, and then annually. Knee Society Score (KSS), knee function score, knee pain score, and knee range of motion (ROM) were assessed.

RESULTS
Among the group, all spacers were easily removed, and bone defect degree showed no obvious change compared with pre-implant, 24 (96%) patients had been debrided once, and 1 patient had been debrided twice before reimplant prosthesis. Mean follow-up was 64.2 (range, 52-89) months. There was no infection recurrence at final follow-up. Compared with preoperative data, the KSS (66 [59, 71], 83 [80, 88] vs 46 [43, 57], P < 0.01), knee function score (43 [42, 49], 78 [73, 82] vs 32 [25, 37], P < 0.01), knee pain score (34 [33, 37], 42 [40, 45] vs 18 [16, 23], P < 0.01), and knee ROM (92° [86°, 96°], 94° [90°, 98°] vs 78° [67°, 86°], P < 0.01) were all improved during follow-up and at final visit. Three patients experienced complications in the interval period: one case had knee dislocation, one had knee instability, and one had a chip in the femoral component of the spacer.

CONCLUSION
Using articulating antibiotic-loaded spacers showed benefits for treating infected TKA in selected patients. No infection recurrence was observed during follow-up.

Tian|Meng-Qiang|MQ| Yang|Xian-Teng|XT| Tian|Xiao-Bin|XB| Sun|Yun-Bo|YB| Duan|Yuan-Hui|YH| Sun|Li|L|

D000368:Aged
D000369:Aged, 80 and over
D000900:Anti-Bacterial Agents
D001172:Arthritis, Rheumatoid
D019645:Arthroplasty, Replacement, Knee
D001843:Bone Cements
D003646:Debridement
D005260:Female
D005500:Follow-Up Studies
D006801:Humans
D007719:Knee Joint
D007720:Knee Prosthesis
D008297:Male
D008875:Middle Aged
D020370:Osteoarthritis, Knee
D011474:Prosthesis Design
D016459:Prosthesis-Related Infections
D011859:Radiography
D016059:Range of Motion, Articular
D020127:Recovery of Function
D012086:Reoperation
D012189:Retrospective Studies
D016896:Treatment Outcome

Two-stage revision
Total knee arthroplasty
Bone cement
Articulating spacer
Delayed infection


Hypertension and Its Associated Factors Among Type 2 Diabetes Mellitus Patients at Debre Tabor General Hospital, Northwest Ethiopia.

Abstract:
Background
Type 2 diabetes mellitus (T2DM) is associated with a high risk of early mortality and morbidity from hypertension. Even though Ethiopia is Africa's first country among the top five in the prevalence of DM, there is a paucity of data on hypertension and its associated factors among patients with type 2 diabetes mellitus. Therefore, this study aimed to determine the prevalence and associated factors of hypertension among type 2 diabetes mellitus patients at Debre Tabor General Hospital, 2019.

Methods and Materials
An institution-based cross-sectional study was employed on 378 T2DM patients. Data were collected using an interviewer-administered questionnaire and analyzed by Stata 14. A multivariable logistic regression model was used to identify associated factors of hypertension among T2DM patients. Associated factors were declared at p < 0.05.

Results
The prevalence of hypertension among T2DM patients was 59.5% (95% CI: 54.5-64.5). Stage 1 hypertension was the most common (30.95%). The odds of hypertension was higher among age group of 50-60 years (adjusted odds ratio (AOR)=2.5, 95% confidence interval (CI) (1.27-4.90)), patients from urban area (AOR = 2.8, 95% CI (1.08-7.18)), with longer duration of T2DM (AOR =1.16, 95% CI (1.08-1.25)), with BMI ≥25 kg/m2 (AOR = 3.2, 95% CI (1.71-5.96)), with poor glycemic control (AOR = 3.0, 95% CI (1.75-5.19)), and patients who were current cigarette smokers (AOR = 3.8, 95% CI (1.98-14.96)).

Conclusion
The prevalence of hypertension is high and the majority have poor blood pressure control. Hence, DM care providers and other health sector stakeholders have to work in collaboration to prevent it through designing appropriate strategies especially for those at higher risk of developing hypertension.

hypertension
associated factors
type 2 diabetes mellitus
Ethiopia


A case report of disseminated histoplasmosis and concurrent cryptococcal meningitis in a patient treated with ruxolitinib.

Abstract:
BACKGROUND
Ruxolitinib is a highly potent janus kinase inhibitor that places its users at risk for various bacterial infections and viral reactivation. However new reports are also emerging that suggest greater immunosuppression and risk for fungal disease.

CASE PRESENTATION
We report the case of a 51 year-old veteran from Guam, treated with ruxolitinib for polycythemia vera, who developed disseminated histoplasmosis and concurrent cryptococcal meningitis.

CONCLUSION
This case draws attention to the degree of immunosuppression that may be seen with this drug and the need for heightened vigilance for opportunistic infections in those treated with inhibitors of janus kinase/signal transducers and activators of transcription (JAK/STAT) such as ruxolitinib.

Histoplasmosis Ruxolitinib Immunosuppression Cryptococcus JAKinhibitor


Interactions between hypertension and inflammatory tone and the effect on blood pressure and outcomes in patients with COVID-19.

Abstract: Arterial hypertension represented one of the most common comorbidities in patients with COVID-19. However, the impact of hypertension on outcome in COVID-19 patients is not clear. Close connections between inflammation and blood pressure (BP) have been described, and inflammation plays a key role in the outcome for patients with COVID-19. Whether hypertension impairs the relationship between inflammation, BP, and outcomes in this context is not known. The aim of this study was to examine the effects of the interactions between inflammation and hypertension status on BP and clinical outcome in patients hospitalized with COVID-19. We designed a retrospective study in 129 patients hospitalized with COVID-19 at Toulouse University Hospital. The hospital outcome was admission to the intensive care unit or death. The inflammatory markers were blood C-reactive protein level (CRP), neutrophil to lymphocyte, and platelet to lymphocyte ratios. We identified strong correlations between CRP (P < .01) and the other inflammatory markers recorded on admission (P < .001) with mean BP within 3 days after admission in normotensive patients, whereas these correlations were absent in patients with hypertension. Also, we observed after multivariate adjustment (P < .05) that CRP level predicted a worse prognosis in hypertensive patients (relative risk 2.52; 95% confidence intervals [1.03- 6.17]; P = .04), whereas CRP was not predictive of outcome in patients without hypertension. In conclusion, the study revealed that in COVID-19 patients, hypertension impairs the relationship between inflammation and BP and interacts with inflammation to affect prognosis. These findings provide insights that could explain the relationship between hypertension and outcomes in COVID-19 patients.

Amar|Jacques|J|0000-0001-9629-9446
Touront|Nicolas|N|
Ciron|Antoine M|AM|
Pendaries|Caroline|C|

hypertension
COVID-19
inflammation
C-reactive protein


Poseidonibacter parvus sp. nov., isolated from a squid.

Abstract: A Gram-stain-negative, aerobic, short rod-shaped, motile, brownish-coloured bacterium, termed strain LPB0137T, was isolated from a squid. Its cells could grow weakly on marine agar 2216 with 0.04 % 2,3,5-triphenyl tetrazolium chloride (TTC). Each cell of strain LPB0137T has a circular chromosome with a length of 2.87 Mb and 27.7 mol% DNA G+C content. The genome includes 2698 protein-coding genes and six rRNA operons. In 16S rRNA gene sequence trees, strain LPB0137T formed a robust monophyletic clade with Poseidonibacter antarcticus SM1702T with a sequence similarity of 98.3 %. However, the average nucleotide identity and in silico DNA-DNA hybridization values between the two type strains were low (83.9 and 28.1 %, respectively). The overall phenotypic and genomic features of strain LPB0137T supported its assignment to the genus Poseidonibacter. However, the relatively low gene and genome sequence similarity between this strain and other type strains of the genus Poseidonibacter and several enzymatic characteristics indicated the taxonomic novelty of the isolated strain as a new member of the genus Poseidonibacter. Therefore, based on the phylogenetic and phenotypic characteristics of LPB0137T, we proposed a novel species of the genus Poseidonibacter for it, with the name Poseidonibacter parvus sp. nov. The type strain of this new species is thus LPB0137T (=KACC 18888T=JCM 31548T).

Kim|Min Ji|MJ|
Baek|Min-Gyung|MG|
Shin|Su-Kyoung|SK|
Yi|Hana|H|

Poseidonibacter parvus
squid
Arcobacter
Arcobacter peruensis


"Motivate to Lactate": Utilizing Motivational Interviewing to Improve Breastfeeding Rates.

Abstract: Promotion of exclusive breastfeeding is a nationwide initiative that has been incorporated into health-care facilities. Staff educators for women's and children's services should consider using motivational interviewing techniques to engage patients in a conversation about breastfeeding. Motivational interviewing has been linked with many positive outcomes in patient-centered care. This research article reveals the staffs' positive perception of adopting these techniques into daily practice and their thoughts on the potential patient outcomes.

lactation
motivational interviewing
breastfeeding
staff education
nurse perception
patient interaction