Impact of an Online Training Program in Smoking Cessation Interventions in Hospitals.

Abstract:
PURPOSE
To assess changes in the self-reported performance of smoking cessation interventions according to the 5A's model (Ask; Advise; Assess; Assist; and Arrange follow-up) among clinicians; and to identify the main barriers and facilitators in smoking cessation implementation before and after an online smoking cessation training program.

DESIGN
Pre-post evaluation.

METHODS
We assessed self-reported smoking cessation interventions in the implementation of the 5A's model among clinicians working in Catalan hospitals (Spain). In addition, we assessed individual-, behavioral-, and organizational-level factors that act as barriers and facilitators in the implementation of the 5A's model. We used a questionnaire of 63 items reflecting each of the 5A's performance (scored from 0 = none to 10 = most possible). The questionnaire was completed both immediately before and 6 months after the training. We analyzed the data of those participants who had a clinical role and answered pre- and post-questionnaires. We used the nonparametric test for paired data (Wilcoxon) to examine changes in scores.

FINDINGS
A total of 127 clinicians completed the pre-post questionnaire; 63.0% were registered nurses, 17.3% were nursing assistants, 7.9% were physicians, and 11.8% were other professionals (p < .001). Overall, there were significant increases in the implementation of the assist component (from a score of 4.5 to 5.2; p < .003) and arrange a follow-up component (from 3.6 to 4.5; p < .001) of the intervention. Scores in the perception of the level of overall preparation, preparedness in using smoking cessation drugs, level of competence, and organizational recognition improved (p < .001) at the follow-up; however, the score in the perception that implementing smoking cessation is part of their job decreased (from 6.3 to 4.4; p < .001).

CONCLUSIONS
The online training had a positive impact on the implementation of assist and arrange follow-up components. Although self-preparedness in the management of smokers increased, the motivation and involvement of key professionals decreased. Organizational factors related to the incorporation of resources (such as protocols, records, etc.) should be improved for the correct progression of smoking cessation interventions within the institutions.

CLINICAL RELEVANCE
Smoking cessation training programs should incorporate some motivational content to increase the engagement of health professionals in smoking cessation interventions in their clinical practice.

Martínez|Cristina|C|0000-0002-0108-3288 Castellano|Yolanda|Y| Andrés|Ana|A| Fu|Marcela|M| Feliu|Ariadna|A| Antón|Laura|L| Ballbè|Montse|M| Fernández|Paz|P| Cabrera|Sandra|S| Riccobene|Ana|A| Gavilan|Eva|E| Baena|Antoni|A| Margalef|Mercè|M| Tigova|Olena|O| Quirós|Núria|N| Guillen|Olga|O| Company|Assumpta|A| Fernández|Esteve|E|

online training
smoking cessation
Barriers
nurses
brief intervention
health organizations
healthcare workers
tobacco cessation


Pharmacokinetic Modeling of Ceftiofur Sodium Using Non-linear Mixed-Effects in Healthy Beagle Dogs.

Abstract: Ceftiofur (CEF) sodium is a third-generation broad-spectrum cephalosporin commonly used in an extra-label manner in dogs for the treatment of respiratory and urinary system infections. To contribute to the literature supporting CEF use in companion animals, we have developed a compartmental, non-linear mixed-effects (NLME) model of CEF pharmacokinetics in dogs (PK). We then used the mathematical model to predict (via Monte Carlo simulation) the duration of time for which plasma concentrations of CEF and its pharmacologically active metabolites remained above minimum inhibitory concentrations (respiratory tract Escherichia coli spp.). Twelve healthy beagle dogs were administered either 2.2 mg/kg ceftiofur-sodium (CEF-Na) intravenously (I.V) or 2.2 mg/kg CEF-Na subcutaneously (S.C). Plasma samples were collected over a period of 72 h post-administration. To produce a measurement of total CEF, both CEF and CEF metabolites were derivatized into desfuroylceftiofur acetamide (DCA) before analysis by UPLC-MS/MS. No adverse effects were reported after I.V or S.C dosing. The NLME PK models were parameterized using the stochastic approximation expectation maximization algorithm as implemented in Monolix 2018R2. A two-compartment mamillary model with first-order elimination and first-order S.C absorption best described the available kinetic data. Final parameter estimates indicate that CEF has a low systemic clearance (0.25 L/h/kg) associated with a low global extraction ratio E = 0.02) and a moderate volume of distribution (2.97 L/kg) in dogs. The absolute bioavailability after S.C administration was high (93.7%). Gender was determined to be a significant covariate in explaining the variability of S.C absorption. Our simulations predicted that a dose of 2.2 mg/kg CEF-Na S.C would produce median plasma concentrations of CEF of at least 0.5 μg/mL (MIC50) for ~30 h.

Wang|Jianzhong|J|
Schneider|Benjamin K|BK|
Xue|Jiao|J|
Sun|Pan|P|
Qiu|Jicheng|J|
Mochel|Jonathan P|JP|
Cao|Xingyuan|X|

pharmacokinetics
ceftiofur sodium
dogs
NLME
monte carlo simulations


Energy drink consumption is associated with reduced sleep quality among college students: a cross-sectional study.

Abstract:
AIM
Intake of caffeinated energy drinks has significantly increased, specifically among young adults and adolescents. College students are prone to developing unhealthy eating habits and dependence on stimulants, which puts them at a greater risk of sleep problems. This study aims to investigate the prevalence of caffeinated energy drink consumption and its association with sleep quality in college students.

METHODS
A sample of 919 randomly selected adults (237 males and 682 females) from various colleges at the University of Sharjah/United Arab Emirates participated in this cross-sectional study. Data were collected using an online validated questionnaire.

RESULTS
The current study revealed that 376 students (41%) were consuming energy drinks on a regular basis. Approximately half of the students had normal sleep patterns; the other half had sleep problems (anxiety and intermittent sleep). Results of the present study revealed a significant (r = -0.10, P < 0.05) relationship between the consumption of energy drinks and sleep quality and patterns.

CONCLUSIONS
Moderate consumption of energy drinks was reported among college students. Consumption of energy drinks was significantly associated with changes in sleep quality and patterns of students.


Order of Activity of Nitrogen, Iron Oxide, and FeNx Complexes towards Oxygen Reduction in Alkaline Medium.

Abstract: In alkaline medium, it seems that both metal-free and iron-containing carbon-based catalysts, such as nitrogen-doped nanocarbon materials, FeOx -doped carbon, and Fe/N/C catalysts, are active for the oxygen reduction reaction (ORR). However, the order of activity of these different active compositions has not been clearly determined. Herein, we synthesized nitrogen-doped carbon black (NCB), Fe3 O4 /CB, Fe3 O4 /NCB, and FeN4 /CB. Through the systematic study of the ORR catalytic activity of these four catalysts in alkaline solution, we confirmed the difference in the catalytic activity and catalytic mechanism for nitrogen, iron oxides, and Fe-N complexes, respectively. In metal-free NCB, nitrogen can improve the ORR catalytic activity with a four-electron pathway. Fe3 O4 /CB catalyst did not exhibit improved activity over that of NCB owing to the poor conductivity and spinel structure of Fe3 O4 . However, FeN4 coordination compounds as the active sites showed excellent ORR catalytic activity.

Zhu|Yansong|Y|
Zhang|Bingsen|B|
Wang|Da-Wei|DW|
Su|Dang Sheng|DS|

nitrogen
iron
carbon
oxygen reduction reaction
electrocatalyst


Effects of serum on cytotoxicity of nano- and micro-sized ZnO particles.

Abstract: Although an increasing number of in vitro studies are being published regarding the cytotoxicity of nanomaterials, the components of the media for toxicity assays have often varied according to the needs of the scientists. Our aim for this study was to evaluate the influence of serum-in this case, fetal bovine serum-in a cell culture medium on the toxicity of nano-sized (50-70 nm) and micro-sized (<1 μm) ZnO on human lung epithelial cells (A549). The nano- and micro-sized ZnO both exhibited their highest toxicity when exposed to serum-free media, in contrast to exposure in media containing 5 or 10 % serum. This mainly comes not only from the fact that ZnO particles in the serum-free media have a higher dosage-per-cell ratio, which results from large aggregates of particles, rapid sedimentation, absence of protein protection, and lower cell growth rate, but also that extracellular Zn2+ release contributes to cytotoxicity. Although more extracellular Zn2+ release was observed in serum-containing media, it did not contribute to nano-ZnO cytotoxicity. Furthermore, non-dissolved particles underwent size-dependent particle agglomeration, resulting in size-dependent toxicity in both serum-containing and serum-free media. A low correlation between cytotoxicity and inflammation endpoints in the serum-free medium suggested that some signaling pathways were changed or induced. Since cell growth, transcription behavior for protein production, and physicochemical properties of ZnO particles all were altered in serum-free media, we recommend the use of a serum-containing medium when evaluating the cytotoxicity of NPs.

Serum
Cytotoxicity
A549
Nanoparticles
Zinc oxide


Elemental distribution in the edible leaves of Celosia trigyna from the western and northern regions of Nigeria.

Abstract: Celosia trigyna, which belongs to the plant family Amaranthaceae, is a plant used in traditional medicine to treat several conditions such as sores, chest pains, diarrhoea and menstrual cramps in many countries in Africa. It is also consumed by the local people in Nigeria as soups, sauces and stews. In this study, the distribution and bioaccumulation of the elements in C. trigyna species and growth soil from the western and northern regions of Nigeria was investigated to determine the effects of geographical location on the uptake of elements by the plant. Elemental concentrations in the leaves from the western region were found to be in decreasing order of Ca > Mg > Fe > Mn > Zn > Cu > Pb > As > Ni. Concentrations of elements in the leaves from the northern region were found to be in decreasing order of Ca > Mg > Fe > Mn > Zn >  Cu > As > Pb > Ni > Co > Cd. Proximate analysis of leaves from both regions compared well with the recommended dietary allowance making the leaves safe for human consumption. Principal component analysis was used to group elements having the same sources irrespective of their geographical locations. Cd, Co and Cr were not detected in the leaves from the western region. Concentrations of As and Pb were above maximum permissible limits in both regions, while Ayegunle and Bida (in the northern region) had the highest concentrations of Cd. The high level of these toxic metals may be attributed to anthropogenic activities. It is therefore important that the Nigerian agricultural extension system emphasizes the dangers of heavy metal contamination in leafy vegetables to farmers. Activities of the manufacturing industries in the study area should be adequately monitored under standard environmental protection laws.

synergistic and antagonistic relationship


Redox-modulated colorimetric detection of ascorbic acid and alkaline phosphatase activity with gold nanoparticles.

Abstract: Gold nanoparticles (AuNPs) exhibit characteristic absorption peaks in the ultraviolet visible region due to their special surface plasmon resonance effect. This characteristic absorption peak would change with the relative colour varying from wine red to orange-yellow upon sequential addition of ascorbic acid (AA) into the mixture of AuNPs and Ag(I). Similar observations also could be found when the hydrolysis product of sodium l-ascorbyl-2-phosphate with alkaline phosphatase (ALP) was used as an alternative to AA. Results of structure characterization confirmed that the phenomena were due to the reduction of Ag(I) to Ag(0) on the surface of AuNPs and the formation of core-shell AuNPs@Ag. Therefore, a colorimetric assay for rapid visual detection of AA and ALP based on redox-modulated silver deposition on AuNPs has been proposed. Under the optimal experimental conditions, the absorbance variation ΔA522 nm /A370 nm of AuNPs was proportional to the concentration of AA (5-60 μmol/L) and ALP (3-18 U/L) with the corresponding detection limit of 2.44 μmol/L for AA and 0.52 U/L for ALP. The assay showed excellent selectivity towards AA and ALP. Moreover, the assay has been applied to detect AA and ALP activity in real samples with satisfying results.

ascorbic acid
alkaline phosphatase
sodium l-ascorbyl-2-phosphate
core-shell AuNPs@Ag
redox-modulated silver deposition


Fostering Educational Research among Medical Teachers: Evaluation of a Faculty Development Program in India.

Abstract:
INTRODUCTION
Medical education can be enormously benefitted from research. Since clinicians/medical teachers are directly involved in teaching learning processes, they should participate in Educational Research (ER) practices to generate evidence and insights about teaching learning. Faculty Development Program (FDP) has a positive influence amongst health professionals and therefore can prove to be of consequence in instilling a strong educational research culture.

AIM
Present study was undertaken to evaluate the efficacy of a Faculty Development Fellowship Program in Medical Education to foster educational research culture amongst medical teachers.

MATERIALS AND METHODS
Study utilized the Kirkpatrick model of program evaluation for evaluating the fellowship program. It aimed to evaluate the third level of the model i.e., "Change in Behaviour" of participants (n=40) after completion of the course. The tool used was a pre-validated survey questionnaire consisting of five items.

RESULTS
Study population was sparsely aware about educational research and had never attempted the same (100%) before joining the fellowship program. A 32.5% faculty with average professional experience of seven years undertook new educational projects after the fellowship and knowledge gained during fellowship program helped them in guiding educational research (coded into four categories) at their workplaces.

CONCLUSION
There is a need, to direct effort towards focused training for educational research through FDPs for medical teachers. This will encourage academicians and clinicians to become active in ER and guide policies in Teaching Learning Practices in Medical Education.

Srivastava|Tripti K|TK|
Waghmare|Lalitbhushan S|LS|
Rawekar|Alka|A|
Mishra|Ved Prakash|VP|

Medical education
Fellowship
Program evaluation


The contradictory inefficacy of methotrexate in hidradenitis suppurativa: a need to revise pathogenesis or acknowledge disease heterogeneity?

Abstract: The pathogenesis of hidradenitis suppurativa (HS) centers around Th17/Treg dysfunction illustrated by lesional elevation of IL-17A, IL-6, and other inflammatory mediators resulting in a chronic feed-forward inflammatory cascade. Similar inflammatory mechanisms have been identified in psoriasis and rheumatoid arthritis (RA) in which traditional immunosuppressants (including methotrexate) are routinely used with reasonable levels of disease control. Methotrexate's mechanism of action in these instances includes downregulation of the Th17 axis via alterations in dendritic cell and T-cell activity and maturation. Published data suggest methotrexate in an ineffective therapy in HS, which does not pair with our current understanding of the mechanisms of disease. The reasons behind this, including are discussed. Some HS patients may benefit from drugs such as methotrexate, and acknowledgment of the potential of disease heterogeneity will allow exploration of which factors may enable identification of such individuals.

methotrexate
Hidradenitis suppurativa
pathogenesis
Th17
acne inversa
efficacy


Using video feedback as a tool in training parent coaches: promising results from a single-subject design.

Abstract: The Attachment and Biobehavioral Catch-up (ABC) parenting program focuses on three intervention targets: increasing parental nurturance, increasing parental synchrony, and decreasing parental frightening behavior. Parent coaches are expected to comment "in the moment" when behaviors relevant to these three targets are observed in sessions. Making in the moment comments is a challenging aspect of intervention, and parent coaches have struggled with their fidelity to this critical intervention component. Thus, we developed a system for coding the frequency and quality of comments from video-recorded session clips on a statement-by-statement level. To help parent coaches refine and maintain their skills in making such comments, they are taught to code segments of their own video-recorded sessions, with the expectation that gains would be seen in comments after learning to code. In this paper, we describe the fidelity coding system and present initial results from a year-long, single-subject design examining the effects of video feedback coding for a parent coach who was learning the intervention. We observed an increase in frequency of in the moment comments during the period of video feedback coding, consistent with a training effect.

Meade|E B|EB|
Dozier|Mary|M|
Bernard|Kristin|K|

video feedback
intervention
fidelity
implementation
in vivo coaching
parent training
supervision


Improving visual communication of discriminative accuracy for predictive models: the probability threshold plot.

Abstract:
Objectives
To propose a visual display-the probability threshold plot (PTP)-that transparently communicates a predictive models' measures of discriminative accuracy along the range of model-based predicted probabilities (Pt).

Materials and Methods
We illustrate the PTP by replicating a previously-published and validated machine learning-based model to predict antihyperglycemic medication cessation within 1-2 years following metabolic surgery. The visual characteristics of the PTPs for each model were compared to receiver operating characteristic (ROC) curves.

Results
A total of 18 887 patients were included for analysis. Whereas during testing each predictive model had nearly identical ROC curves and corresponding area under the curve values (0.672 and 0.673), the visual characteristics of the PTPs revealed substantive between-model differences in sensitivity, specificity, PPV, and NPV across the range of Pt.

Discussion and Conclusions
The PTP provides improved visual display of a predictive model's discriminative accuracy, which can enhance the practical application of predictive models for medical decision making.

Johnston|Stephen S|SS|
Fortin|Stephen|S|
Kalsekar|Iftekhar|I|
Reps|Jenna|J|
Coplan|Paul|P|

discriminative accuracy
predictive analytics
receiver operating characteristic curve


Molecular insights into psychedelic drug action.

Abstract: A confluence of factors has renewed interest in the scientific understanding and translational potential of psychedelic drugs such as lysergic acid diethylamide (LSD), mescaline, and psilocybin: the desire for additional approaches to mental health care, incremental progress in basic and clinical research, and the reconsideration and relaxation of existing drug policies. With the United States Food and Drug Administration's designation of psilocybin as a "Breakthrough Therapy" for treatment-resistant depression, a new path has been forged for the conveyance of psychedelics to the clinic. Essential to the further development of such applications, however, is a clearer understanding of how these drugs exert their effects at the molecular level. Here we review the current knowledge regarding the molecular details of psychedelic drug actions and suggest that these discoveries can facilitate new insights into their hallucinogenic and therapeutic mechanisms.

psychedelics
G protein-coupled receptors (GPCR)
neurons
serotonin
special issue


Toward mHealth Brief Contact Interventions in Suicide Prevention: Case Series From the Suicide Intervention Assisted by Messages (SIAM) Randomized Controlled Trial.

Abstract:
BACKGROUND
Research indicates that maintaining contact either via letter or postcard with at-risk adults following discharge from care services after a suicide attempt (SA) can reduce reattempt risk. Pilot studies have demonstrated that interventions using mobile health (mHealth) technologies are feasible in a suicide prevention setting.

OBJECTIVE
The aim of this study was to report three cases of patients recruited in the Suicide Intervention Assisted by Messages (SIAM) study to describe how a mobile intervention may influence follow-up.

METHODS
SIAM is a 2-year, multicenter randomized controlled trial conducted by the Brest University Hospital, France. Participants in the intervention group receive SIAM text messages 48 hours after discharge, then at day 8 and day 15, and months 1, 2, 3, 4, 5, and 6. The study includes participants aged 18 years or older, who have attended a participating hospital for an SA, and have been discharged from the emergency department (ED) or a psychiatric unit (PU) for a stay of less than 7 days. Eligible participants are randomized between the SIAM intervention messages and a control group. In this study, we present three cases from the ongoing SIAM study that demonstrate the capability of a mobile-based brief contact intervention for triggering patient-initiated contact with a crisis support team at various time points throughout the mobile-based follow-up period.

RESULTS
Out of the 244 patients recruited in the SIAM randomized controlled trial, three cases were selected to illustrate the impact of mHealth on suicide risk management. Participants initiated contact with the emergency crisis support service after receiving text messages up to 6 months following discharge from the hospital. Contact was initiated immediately following receipt of a text message or up to 6 days following a message.

CONCLUSIONS
This text message-based brief contact intervention has demonstrated the potential to reconnect suicidal individuals with crisis support services while they are experiencing suicidal ideation as well as in a period after receiving messages. As follow-up phone calls over an extended period of time may not be feasible, this intervention has the potential to offer simple technological support for individuals following discharge from the ED.

TRIAL REGISTRATION
ClinicalTrials.gov NCT02106949; https://clinicaltrials.gov/ct2/show/NCT02106949 (Archived by WebCite at http://www.webcitation.org/6wMtAFL49).

Suicide
Text Messaging
Cell Phone
Electronic Health Records
Secondary Prevention
Tertiary Prevention


Adjusted Particle Size Eliminates the Need of Linkage of Antigen and Adjuvants for Appropriated T Cell Responses in Virus-Like Particle-Based Vaccines.

Abstract: Since the discovery of the first virus-like particle (VLP) derived from hepatitis B virus in 1980 (1), the field has expanded substantially. Besides successful use of VLPs as safe autologous virus-targeting vaccines, the powerful immunogenicity of VLPs has been also harnessed to generate immune response against heterologous and even self-antigens (2-4). Linking adjuvants to VLPs displaying heterologous antigen ensures simultaneous delivery of all vaccine components to the same antigen-presenting cells. As a consequence, antigen-presenting cells, such as dendritic cells, will process and present the antigen displayed on VLPs while receiving costimulatory signals by the VLP-incorporated adjuvant. Similarly, antigen-specific B cells recognizing the antigen linked to the VLP are simultaneously exposed to the adjuvant. Here, we demonstrate in mice that physical association of antigen, carrier (VLPs), and adjuvant is more critical for B than T cell responses. As a model system, we used the E7 protein from human papilloma virus, which spontaneously forms oligomers with molecular weight ranging from 158 kDa to 10 MDa at an average size of 50 nm. E7 oligomers were either chemically linked or simply mixed with VLPs loaded with DNA rich in non-methylated CG motifs (CpGs), a ligand for toll-like receptor 9. E7-specific IgG responses were strongly enhanced if the antigen was linked to the VLPs. In contrast, both CD4+ and CD8+ T cell responses as well as T cell-mediated protection against tumor growth were comparable for linked and mixed antigen formulations. Therefore, our data show that B cell but not T cell responses require antigen-linkage to the carrier and adjuvant for optimal vaccination outcome.

Gomes|Ariane C|AC|
Flace|Anna|A|
Saudan|Philippe|P|
Zabel|Franziska|F|
Cabral-Miranda|Gustavo|G|
Turabi|Aadil El|AE|
Manolova|Vania|V|
Bachmann|Martin F|MF|


Preservation of the lung after 4-year compression by fibrous tumors of pleura.

Abstract: Solitary fibrous tumor of the pleura is a neoplasm arising from mesenchymal tissue, which may cause dyspnea and cough. Computed tomography in a 72-year-old woman, who had been diagnosed with a 3-cm mass in the left upper lung 24 years previously, identified 15- and 10-cm tumors, with complete collapse of the lingula and lower lobe. The tumors were successfully excised with partial lung resection, and the collapsed lung was preserved. There was no recurrence or atelectasis at 4 years postoperatively.

Ishibashi|Hironori|H| Takahashi|Ken|K| Kumazawa|Sachiko|S| Okubo|Kenichi|K|

Pleura
Solitary fibrous tumor
Fibroma
Pleural neoplasms
Pulmonary atelectasis
pleural


Tear film inflammatory cytokine upregulation in contact lens discomfort.

Abstract:
PURPOSE
To investigate the ocular inflammatory response, using clinical and immunological techniques, in people experiencing contact lens (CL) discomfort.

METHODS
This study involved 38 adults who were full-time, silicone-hydrogel CL wearers. Participants were categorized into groups based upon a validated CL dry-eye questionnaire (CLDEQ-8) (n = 17 'asymptomatic', CLDEQ-8 score <9; n = 21 'symptomatic', CLDEQ-8 score ≥13). Examinations were performed at two visits (one with, and one without, CL wear), separated by one-week. Testing included: tear osmolarity, ocular redness, tear stability, ocular surface staining, meibography, tear production and tear collection. Tear osmolarity was taken from the inferior-lateral and superior-lateral menisci. The 'Inferior-Superior Osmotic Difference', I-SOD, was the absolute osmolarity difference between these menisci. Concentrations of seven cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-gamma, TNF-alpha) were assayed from basal tears using multiplex cytometric bead array.

RESULTS
At baseline, there was no significant difference in key clinical signs between asymptomatic and symptomatic CL wearers (p > 0.05). The I-SOD was greater in symptomatic than asymptomatic CL wearers (23.1 ± 2.6 versus 11.3 ± 1.4 mOsmol/L, p = 0.001). People experiencing CL discomfort had higher tear IL-17A (122.6 ± 23.7 versus 44.0 ± 10.0 pg/mL, p = 0.02) and reduced tear stability (6.3 ± 1.1 versus 10.4 ± 1.6 s, p = 0.03) after several hours of CL wear. Tear IL-17A levels correlated with both the I-SOD (r = 0.43, p = 0.01) and CLDEQ-8 score (r = 0.40, p = 0.01).

CONCLUSIONS
CL discomfort occurs in individuals having no clinical dry eye signs, and is associated with higher tear levels of the pro-inflammatory cytokine IL-17A. These findings support an association between the discomfort response and low-grade, ocular surface inflammation.

Gad|Anne|A|
Vingrys|Algis Jonas|AJ|
Wong|Chinn Yi|CY|
Jackson|David Charles|DC|
Downie|Laura Elizabeth|LE|

Tear film
Cytokine
Contact lens
Contact lens discomfort
Ocular surface
IL-17A
Inflammation
Interleukin


MLF1IP is correlated with progression and prognosis in luminal breast cancer.

Abstract: Myeloid leukemia factor 1-interacting protein (MLF1IP) has been found to be involved in the progression of several malignancies. The potential correlation between MLF1IP and clinical outcome in patients with luminal breast cancer, however, remains unknown. In the present study, we demonstrated that MLF1IP was significantly upregulated in luminal breast cancer tissue compared with adjacent normal tissue both in validated cohort and TCGA cohort. Upregulated expression of MLF1IP was correlated with more often lymph node metastasis and negative progesterone receptor expression in TCGA cohorts. Kaplan-Meier analysis indicated that patients with high MLF1IP expression had significantly lower overall survival. Moreover, multivariate analysis revealed that high MLF1IP expression was independent high risk factor as well as old age (>60) and distant metastasis. This study provides new insights and evidences that MLF1IP over-expression plays important roles in progression of luminal breast cancer. However, the precise cellular mechanisms for MLF1IP in luminal breast cancer need to be further explored.


Potential applications of keratinocytes derived from human embryonic stem cells.

Abstract: Although skin grafting is one of the most advanced cell therapy technique, wide application of skin substitutes is hampered by the difficulty in securing sufficient amount of epidermal substitute. Additionally, in understanding the progression of skin aging and disease, and in screening the cosmetic and pharmaceutical products, there is lack of a satisfactory human skin-specific in vitro model. Recently, human embryonic stem cells (hESCs) have been proposed as an unlimited and reliable cell source to obtain almost all cell types present in the human body. This review focuses on the potential off-the-shelf use of hESC-derived keratinocytes for future clinical applications as well as a powerful in vitro skin model to study skin function and integrity, host-pathogen interactions and disease pathogenesis. Furthermore, we discuss the industrial applications of hESC-derived keratinized multi-layer epithelium which provides a human-like test platform for understanding disease pathogenesis, evaluation of new therapeutic modalities and assessment of the safety and efficacy of skin cosmetics and therapeutics. Overall, we conclude that the hESC-derived keratinocytes have great potential for clinical, research and industrial applications.

Movahednia|Mohammad M|MM|
Kidwai|Fahad K|FK|
Jokhun|Doorgesh S|DS|
Squier|Christopher A|CA|
Toh|Wei Seong|WS|
Cao|Tong|T|

Human embryonic stem cell
In vitro skin platform
Keratinocyte differentiation
Multi-lineage hESCepithelium


The Role of Blinks, Microsaccades and their Retinal Consequences in Bistable Motion Perception.

Abstract: Eye-related movements such as blinks and microsaccades are modulated during bistable perceptual tasks. However, if they play an active role during internal perceptual switches is not known. We conducted two experiments involving an ambiguous plaid stimulus, wherein participants were asked to continuously report their percept, which could consist of either unidirectional coherent or bidirectional component movement. Our main results show that blinks and microsaccades did not facilitate perceptual switches. On the contrary, a reduction in eye movements preceded the perceptual switch. Blanks, on the other hand, thought to mimic the retinal consequences of a blink, consistently led to a switch. Through the timing of the blank-introduced perceptual change, we were able to estimate the delay between the internal switch and the response. This delay further allowed us to evaluate that the reduction in blink probability co-occurred with the internal perceptual switch. Additionally, our results indicate that distinct internal processes underlie the switch to coherent vs. component percept. Blanks exclusively facilitated a switch to the coherent percept, and only the switch to coherent percept was followed by an increase in blink rate. In a second study, we largely replicated the findings and included a microsaccade analysis. Microsaccades only showed a weak relation with perceptual switches, but their direction was correlated with the perceived motion direction. Nevertheless, our data suggests an interaction between microsaccades and blinks by showing that microsaccades were differently modulated around blinks compared with blanks. This study shows that a reduction in eye movements precedes internal perceptual switches indicating that the rate of blinks can set the stage for a reinterpretation of sensory input. While a perceptual switch based on changed sensory input usually leads to an increase in blink rate, such an increase was only present after the perceptual switch to coherent motion but absent after the switch to component percept. This provides evidence of different underlying mechanism or internal consequence of the two perceptual switches and suggests that blinks can uncover differences in internal percept-related processes that are not evident from the percept itself.

eye movements
ambiguous plaid 4
bistable perception
microsaccade direction
microsaccade rate
spontaneous eye blink


A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers.

Abstract: Single nucleotide polymorphisms (SNPs) in DNA glycosylase genes involved in the base excision repair (BER) pathway can modify breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We previously found that SNP rs34259 in the uracil-DNA glycosylase gene (UNG) might decrease ovarian cancer risk in BRCA2 mutation carriers. In the present study, we validated this finding in a larger series of familial breast and ovarian cancer patients to gain insights into how this UNG variant exerts its protective effect. We found that rs34259 is associated with significant UNG downregulation and with lower levels of DNA damage at telomeres. In addition, we found that this SNP is associated with significantly lower oxidative stress susceptibility and lower uracil accumulation at telomeres in BRCA2 mutation carriers. Our findings help to explain the association of this variant with a lower cancer risk in BRCA2 mutation carriers and highlight the importance of genetic changes in BER pathway genes as modifiers of cancer susceptibility for BRCA1 and BRCA2 mutation carriers.

D020022:Genetic Predisposition to Disease

BRCA2
uracil-DNA glycosylase
DNA damage
oxidative stress susceptibility
cancer risk modifier
telomere damage


Three-dimensional visualization as a tool for interpreting locomotion strategies in ophiuroids from the Devonian Hunsrück Slate.

Abstract: Living brittle stars (Echinodermata: Ophiuroidea) employ a very different locomotion strategy to that of any other metazoan: five or more arms coordinate powerful strides for rapid movement across the ocean floor. This mode of locomotion is reliant on the unique morphology and arrangement of multifaceted skeletal elements and associated muscles and other soft tissues. The skeleton of many Palaeozoic ophiuroids differs markedly from that in living forms, making it difficult to infer their mode of locomotion and, therefore, to resolve the evolutionary history of locomotion in the group. Here, we present three-dimensional digital renderings of specimens of six ophiuroid taxa from the Lower Devonian Hunsrück Slate: four displaying the arm structure typical of Palaeozoic taxa (Encrinaster roemeri, Euzonosoma tischbeinianum, Loriolaster mirabilis, Cheiropteraster giganteus) and two (Furcaster palaeozoicus, Ophiurina lymani) with morphologies more similar to those in living forms. The use of three-dimensional digital visualization allows the structure of the arms of specimens of these taxa to be visualized in situ in the round, to our knowledge for the first time. The lack of joint interfaces necessary for musculoskeletally-driven locomotion supports the interpretation that taxa with offset ambulacrals would not be able to conduct this form of locomotion, and probably used podial walking. This approach promises new insights into the phylogeny, functional morphology and ecological role of Palaeozoic brittle stars.

locomotion
ophiuroid
three-dimensional imaging


Fluorescence live cell imaging.

Abstract: Fluorescence microscopy of live cells has become an integral part of modern cell biology. Fluorescent protein (FP) tags, live cell dyes, and other methods to fluorescently label proteins of interest provide a range of tools to investigate virtually any cellular process under the microscope. The two main experimental challenges in collecting meaningful live cell microscopy data are to minimize photodamage while retaining a useful signal-to-noise ratio and to provide a suitable environment for cells or tissues to replicate physiological cell dynamics. This chapter aims to give a general overview on microscope design choices critical for fluorescence live cell imaging that apply to most fluorescence microscopy modalities and on environmental control with a focus on mammalian tissue culture cells. In addition, we provide guidance on how to design and evaluate FP constructs by spinning disk confocal microscopy.

D000818:Animals
D002478:Cells, Cultured
D049452:Green Fluorescent Proteins
D006801:Humans
D018613:Microscopy, Confocal
D008856:Microscopy, Fluorescence
D038761:Photobleaching
D059629:Signal-To-Noise Ratio
D059010:Single-Cell Analysis

Fluorescence microscopy
Fluorescent proteins
Live cell microscopy
Environmental control
Spinning disk confocal microscopy
Photobleaching


Association Analysis of NLRP3 Inflammation-Related Gene Promotor Methylation as Well as Mediating Effects on T2DM and Vascular Complications in a Southern Han Chinese Population.

Abstract: Objective: To explore the association between the methylation levels in the promoter regions of the NLRP3, AIM2, and ASC genes and T2DM and its vascular complications in a Southern Han Chinese population and further analyze their interaction and mediating effects with environmental factors in T2DM. Methods: A case-control study was used to determine the association between population characteristics, the methylation level in the promoter region of the NLRP3, AIM2, and ASC genes and T2DM and vascular complications. A mediating effect among genes-environment-T2DM and the interaction of gene-gene or gene-environment factors was explored. Results: In the logistic regression model with adjusted covariants, healthy people with lower total methylation levels in the AIM2 promoter region exhibited a 2.29-fold [OR: 2.29 (1.28~6.66), P = 0.011] increased risk of developing T2DM compared with higher-methylation individuals. T2DM patients without any vascular complications who had lower methylation levels (<methylation median) in NLRP3 CpG2 and AIM2 total methylation had 6.45 (OR: 6.45, 95% CI: 1.05~39.78, P = 0.011) and 9.48 (OR: 9.48, 95% CI: 1.14~79.00, P = 0.038) times higher risks, respectively, of developing diabetic microvascular complications than T2DM patients with higher methylation. Similar associations were also found between the lower total methylation of the NLRP3 and AIM2 promoter regions and macrovascular complication risk (NLRP3 OR: 36.03, 95% CI: 3.11~417.06, P = 0.004; AIM2 OR: 30.90, 95% CI: 2.59~368.49, P = 0.007). Lower NLRP3 promoter total methylation was related to a 17.78-fold increased risk of micro-macrovascular complications (OR: 17.78, 95% CI: 2.04~155.28, P = 0.009). Lower ASC CpG1 or CpG3 methylation levels had significant partial mediating effects on T2DM vascular complications caused by higher age (ASC CpG1 explained approximately 52.8% or 32.9% of the mediating effect of age on macrovascular or macro-microvascular complications; ASC CpG3 explained approximately 38.9% of the mediating effect of age on macrovascular complications). No gene-gene or gene-environment interaction was identified in T2DM. Conclusion: Lower levels of AIM2 promoter total methylation might increase the risk of T2DM. NLRP3, AIM2, and ASC promoter total methylation or some CpG methylation loss might increase the risk of T2DM vascular complications, which merits further study to support the robustness of these findings.

Zhou|Zixing|Z| Wang|Lijun|L| Wen|Zihao|Z| Zheng|Shaoling|S| Ye|Xiaohong|X| Liu|Dandan|D| Wu|Jing|J| Zou|Xiaoqian|X| Liu|Yumei|Y| Wang|Yao|Y| Dong|Shirui|S| Huang|Xiuxia|X| Du|Xiuben|X| Zhu|Kehui|K| Chen|Xiaojing|X| Huang|Shiqi|S| Zeng|Chengli|C| Han|Yajing|Y| Zhang|Baohuan|B| Nie|Lihong|L| Yang|Guang|G| Jing|Chunxia|C|


Effects of performing dual tasks on postural sway and postural control complexity in people with haemophilic arthropathy.

Abstract:
INTRODUCTION
People with haemophilic arthropathy (PWHA) have impairments in postural control. However, little is known about the effects of demanding conditions, including the unipedal stance and dual tasks, on postural control in PWHA.

AIM
Determine the effects of performing dual tasks while in the one-leg stance on postural sway and postural control complexity in PWHA vs. healthy active (HAG) and non-active (HNAG) groups of individuals.

METHODS
Fifteen PWHA and 34 healthy subjects (18 active and 16 non-active) were recruited. Vertical (V), mediolateral (ML) and anteroposterior (AP) centre of mass signals were acquired using a 3-axis accelerometer placed at the L3/L4 vertebrae of subjects as they performed the one-leg stance under single and dual-task conditions. Sway balance and the complexity of postural control were studied via root mean square (RMS) acceleration and sample entropy, respectively. Increased complexity of postural sway was attributed to increased automatism of postural control.

RESULTS
RMS values for PWHA were higher than HAG under both conditions for the V and ML axes, and higher than HNAG under the dual-task condition for the ML axis. Sample entropy was lower in PWHA than healthy individuals under the dual-task condition for V and ML axes, and the single-task condition for the ML axis (P < .05).

CONCLUSION
PWHA had poorer postural sway and decreased postural control complexity when performing a one-leg stance than healthy people, especially when the dual-task condition was applied. These results may help to design new approaches to assess and improve postural control in PWHA.

postural control
centre of mass
sample entropy
accelerometry
haemophilia
motor control


Adaptation of the Cutaneous Microcirculation in Preterm Neonates.

Abstract:
OBJECTIVE
Transition from fetal to neonatal circulation is characterized by multiple hemodynamic changes. The role of the microcirculation in this process is underexposed. Visualizing the cutaneous microcirculation can help us understand peripheral perfusion in a noninvasive manner.

METHODS
Cutaneous microcirculation of term and preterm infants born below 32 weeks of GA was measured in the first month of life using IDF imaging. Linear mixed modeling was used to identify clinical variables which influence the cutaneous microcirculation.

RESULTS
Sixty preterm and 33 term infants were included. TVD of preterm infants significantly decreased in the first month of life (31.7 mm/mm(2)  day 1 vs 27.9 mm/mm(2)  day 28), but remained significantly higher compared to TVD of term infants on day 1 (25.8 mm/mm(2) ). Besides postnatal age, no clinical variables were associated with TVD. Infants born SGA had significantly higher TVD values directly after birth than those born appropriate for GA (35.4 mm/mm(2) vs 31.6 mm/mm(2) ; p = 0.015).

CONCLUSIONS
TVD decreases in the first month after birth and is higher in preterm infants compared to those born term. Differences in antenatal oxygen exposure might explain the adaptation of the microcirculation.

van Elteren|Hugo A|HA|
de Jonge|Rogier C J|RC|
van Rosmalen|Joost|J|
Ince|Can|C|
Reiss|Irwin K M|IK|

adaptation
cutaneous
preterm
neonates
incident dark field


Hydrogen Generation from Additive-Free Formic Acid Decomposition Under Mild Conditions by Pd/C: Experimental and DFT Studies.

Abstract: Safe and efficient hydrogen generation and storage has received much attention in recent years. Herein, a commercial 5 wt% Pd/C catalyst has been investigated for the catalytic, additive-free decomposition of formic acid at mild conditions, and the experimental parameters affecting the process systematically have been investigated and optimised. The 5 wt% Pd/C catalyst exhibited a remarkable 99.9% H2 selectivity and a high catalytic activity (TOF = 1136 h-1) at 30 °C toward the selective dehydrogenation of formic acid to H2 and CO2. The present commercial catalyst demonstrates to be a promising candidate for the efficient in-situ hydrogen generation at mild conditions possibiliting practical applications of formic acid systems on fuel cells. Finally DFT studies have been carried out to provide insights into the reactivity and decomposition of formic acid along with the two-reaction pathways on the Pd (111) surface.

Sanchez|Felipe|F| Motta|Davide|D| Roldan|Alberto|A| Hammond|Ceri|C| Villa|Alberto|A| Dimitratos|Nikolaos|N|

Formic acid decomposition
DFT calculations
Green chemistry
H2 production
Pd nanoparticles
Renewable feedstock


Postrelease mortality among persons hospitalized during their incarceration.

Abstract:
PURPOSE
Health and mortality of people released from incarceration have received increased attention, and yet little is known about the postrelease experiences of those hospitalized during incarceration.

METHODS
For persons incarcerated and released from the North Carolina (NC) state prison system between January 1, 2008, and June 30, 2015, we examined postrelease mortality from 2008 to 2016 by history of prison hospitalization.

RESULTS
Among 111,479 released persons, 0.9% (n = 1010) were hospitalized during their incarceration, and of those, 10.5% (n = 106) died during follow-up compared with 3.2% (3511/110,469) of other released persons. Those hospitalized in prison had a higher postrelease death rate (adjusted hazard ratio: 2.44), a lower 8-year conditional probability of survival (0.80 vs. 0.94), and were more likely to die from chronic causes (79.2% vs. 51.0%) than other released persons. The postrelease standardized mortality rate among men hospitalized in prison was 3.1 times higher than that of those not hospitalized and 7.1 times the rate of all NC men.

CONCLUSIONS
People hospitalized during incarceration constitute a particularly vulnerable, yet relatively easily identifiable priority population to focus health interventions supporting continuity of care after prison release. Yet such efforts may be particularly challenging in NC and other Medicaid non-expansion states.

Rosen|David L|DL|
Kavee|Andrew L|AL|
Brinkley-Rubinstein|Lauren|L|

Mortality
Medicaid
Incarceration release


Effectiveness of Facebook Groups to Boost Participation in a Parenting Intervention.

Abstract: Although family-based prevention programs have been shown to be effective at reducing adolescent substance use, it is often difficult and costly to recruit and retain parents in programs administered in person. The current study tested whether program engagement and parenting practices could be improved by offering parents in a self-directed family program access to a private Facebook group. Parents of middle school children (N = 103) were recruited through paid Facebook ads to a 5-week self-directed teen substance use prevention program to be completed at home together by parents and their children. Two thirds of parents (N = 72) were randomly assigned to a moderated private Facebook group that provided a forum for parents in the study to interact with each other, and one third (N = 31) were randomized to use the intervention materials without additional support. Relatively few parents participated in the Facebook group and most did not find the experience useful. However, satisfaction with the program assessed 3 months after program completion was high among all parents and most parents engaged with the materials, irrespective of Facebook group assignment. Overall, parents reported significantly lower conflict and more household rules 6 months post-intervention compared to baseline. Parenting practices did not change more among those assigned to the Facebook group than among parents who used the materials on their own. The current findings suggest that providing opportunities for parents to interact online while participating in a self-directed family intervention may not help to increase engagement or improvements in parenting practices, particularly when few parents engage with each other.

Epstein|Marina|M|
Oesterle|Sabrina|S|
Haggerty|Kevin P|KP|

Facebook groups
Parenting intervention
Parenting practices
Facebook recruiting


International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE): Contributions to Understanding the Global Obesity Epidemic.

Abstract: The purpose of this review is to summarize the scientific contributions of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) in extending our understanding about obesity in children from around the world. ISCOLE was a multi-national study of 9 to 11 year-old children from sites in 12 countries from all inhabited continents. The primary purpose was to investigate relationships between lifestyle behaviors and obesity, and the influence of higher-order characteristics such as behavioral settings, and physical, social and policy environments. ISCOLE has made several advances in scientific methodology related to the assessment of physical activity, dietary behavior, sleep and the neighborhood and school environments. Furthermore, ISCOLE has provided important evidence on (1) epidemiological transitions in obesity and related behaviors, (2) correlates of obesity and lifestyle behaviors at the individual, neighborhood and school levels, and (3) 24-h movement behaviors in relation to novel analytical techniques. A key feature of ISCOLE was the development of a platform for international training, data entry, and data quality for multi-country studies. Finally, ISCOLE represents a transparent model for future public-private research partnerships across low, middle and high-income countries.

epidemiological transition
collaboration
overweight
pediatric


A bispecific antibody against two different epitopes on hepatitis B surface antigen has potent hepatitis B virus neutralizing activity.

Abstract: Treatment of chronic hepatitis B virus (HBV) infection with interferon and viral reverse transcriptase inhibitor regimens results in poor viral clearance, loss of response, and emergence of drug-resistant mutant virus strains. These problems continue to drive the development of new therapeutic approaches to combat HBV. Here, we engineered a bispecific antibody using two monoclonal antibodies cloned from hepatitis B surface antigen (HBsAg)-specific memory B cells from recombinant HBsAg-vaccinated healthy volunteers. Next, we evaluated its efficacy in neutralizing HBV in HepaRG cells. This bispecific antibody, denoted as C4D2-BsAb, had superior HBV-neutralizing activity compared with the combination of both parental monoclonal antibodies, possibly through steric hindrance or induction of HBsAg conformational changes. Moreover, C4D2-BsAb has superior endocytotic characteristics into hepatocytes, which inhibits the secretion of HBsAg. These results suggest that the anti-HBsAg bispecific antibody may be an effective treatment method against HBV infection.

Tan|Wenlong|W| Meng|Yanchun|Y| Li|Hui|H| Chen|Yang|Y| Han|Siqi|S| Zeng|Jing|J| Huang|Ang|A| Li|Bohua|B| Zhang|Yanyun|Y| Guo|Yajun|Y|

D000595:Amino Acid Sequence
D018033:Antibodies, Bispecific
D015153:Blotting, Western
D045744:Cell Line, Tumor
D000939:Epitopes
D006514:Hepatitis B Surface Antigens
D006515:Hepatitis B virus
D006801:Humans
D010455:Peptides

bispecific antibody
hepatitis B virus
neutralizing activity
steric hindrance
conformational change
endocytosis


An Efficient Transient Expression System for Enhancing the Generation of Monoclonal Antibodies in 293 Suspension Cells.

Abstract:
BACKGROUND
Recombinant monoclonal antibodies (mAbs) are useful in research, diagnosis, and therapy. The increased demands of recombinant mAbs require efficient production systems. A variety of expression vectors have been developed for stable or transient production of mAbs in mammalian cells. Although a few commercial expression systems of mAbs can be listed, the high expense often impedes academic research.

METHODS
In this study, we described the development of a transient mammalian system based on a bicistronic vector, which contained an internal ribosome entry site (IRES) and enhancer elements to express the IgG1 light chain (LC) and heavy chain (HC) in one transcript. Optimization of all components of the expression system, including gene transfer methods and regulatory elements, yielded maximal expression levels in serum-free 293 suspension cells (Freestyle 293-F).

RESULTS
This method enabled consistent production of the anti-programmed cell death protein 1 (PD-1) mAb up to 300 mg/L in less than one week under transiently transfected conditions. Furthermore, purified anti-PD-1 IgGs showed specific affinity to the target antigen human PD-1 and PHA-stimulated human T cells.

CONCLUSION
The simplicity of the procedure made it suitable for the fast and high-yield production of IgG antibodies in small scales, which expedited the screening of a large number of recombinant candidates.

Zhang|Guoquan|G| Liu|Jie|J| Fan|Wanting|W| Chen|Qianyi|Q| Shi|Bin|B|

D061026:Programmed Cell Death 1 Receptor

transient expression
Antibody
293 suspension cell
PD-1
human β-globin intron
mammalian expression


One-stage Operation with Ipsilateral Two-Piece Craniotomies for a Case of Subarachnoid Hemorrhage with Multiple Intracranial Aneurysms.

Abstract: Subarachnoid hemorrhage (SAH) with multiple intracranial aneurysms is common, but the difficulties often arise in determining treatment strategy in the acute phase. We experienced a case of SAH with distal anterior cerebral artery aneurysm coexisting with middle cerebral artery and anterior communicating artery aneurysms, in which it was difficult to identify the precise rupture site preoperatively, and both pterional approach and interhemispheric approach were required in the acute phase of SAH. However, we could treat whole aneurysms in one stage and obtained an excellent outcome using our surgical procedure with ipsilateral frontotemporal and frontal parasagittal craniotomies through a single skin incision.

subarachnoid hemorrhage
multiple
intracranial
Aneurysm
clipping


Improving the Primary Care Consultation for Diabetes and Depression Through Digital Medical Interview Assistant Systems: Narrative Review.

Abstract:
BACKGROUND
Digital medical interview assistant (DMIA) systems, also known as computer-assisted history taking (CAHT) systems, have the potential to improve the quality of care and the medical consultation by exploring more patient-related aspects without time constraints and, therefore, acquiring more and better-quality information prior to the face-to-face consultation. The consultation in primary care is the broadest in terms of the amount of topics to be covered and, at the same time, the shortest in terms of time spent with the patient.

OBJECTIVE
Our aim is to explore how DMIA systems may be used specifically in the context of primary care, to improve the consultations for diabetes and depression, as exemplars of chronic conditions.

METHODS
A narrative review was conducted focusing on (1) the characteristics of the primary care consultation in general, and for diabetes and depression specifically, and (2) the impact of DMIA and CAHT systems on the medical consultation. Through thematic analysis, we identified the characteristics of the primary care consultation that a DMIA system would be able to improve. Based on the identified primary care consultation tasks and the potential benefits of DMIA systems, we developed a sample questionnaire for diabetes and depression to illustrate how such a system may work.

RESULTS
A DMIA system, prior to the first consultation, could aid in the essential primary care tasks of case finding and screening, diagnosing, and, if needed, timely referral to specialists or urgent care. Similarly, for follow-up consultations, this system could aid with the control and monitoring of these conditions, help check for additional health issues, and update the primary care provider about visits to other providers or further testing. Successfully implementing a DMIA system for these tasks would improve the quality of the data obtained, which means earlier diagnosis and treatment. Such a system would improve the use of face-to-face consultation time, thereby streamlining the interaction and allowing the focus to be the patient's needs, which ultimately would lead to better health outcomes and patient satisfaction. However, for such a system to be successfully incorporated, there are important considerations to be taken into account, such as the language to be used and the challenges for implementing eHealth innovations in primary care and health care in general.

CONCLUSIONS
Given the benefits explored here, we foresee that DMIA systems could have an important impact in the primary care consultation for diabetes and depression and, potentially, for other chronic conditions. Earlier case finding and a more accurate diagnosis, due to more and better-quality data, paired with improved monitoring of disease progress should improve the quality of care and keep the management of chronic conditions at the primary care level. A somewhat simple, easily scalable technology could go a long way to improve the health of the millions of people affected with chronic conditions, especially if working in conjunction with already-established health technologies such as electronic medical records and clinical decision support systems.

D020000:Decision Support Systems, Clinical

digital medical interview assistant, computer-assisted history taking


Cervical spinal glioblastoma multiforme in the elderly.

Abstract: Spinal glioblastoma multiforme (GBM) is uncommon, and its diagnosis may be challenging. This is especially true in the elderly population. Best management strategy remains to be defined. The purpose of this report is to document this rare condition, increase awareness (as a potential differential diagnosis) and propose treatment options in the elderly; a review of the relevant literature is included. A biopsy may be beneficial in given circumstances as cervical spinal GBM carries a better prognosis compared with intramedullary metastasis.

CNS cancer
cancer intervention
neurooncology
neurosurgery
spinal cord


Investigating the relationship between social care supply and healthcare utilization by older people in England.

Abstract: Since 2010, adult social care spending in England has fallen significantly in real terms whilst demand has risen. Reductions in social care supply may also have impacted demand for NHS services, particularly for those whose care is provided at the interface of the health and care systems. We analyzed a panel dataset of 150 local authorities (councils) to test potential impacts on hospital utilization by people aged 65 and over: emergency admission rates for falls and hip fractures ("front-door" measures); and extended stays of 7 days or longer; and 21 days or longer ("back-door" measures). Changes in social care supply were assessed in two ways: gross current expenditure (per capita 65 and over) adjusted by local labor costs and social care workforce (per capita 18 and over). We ran negative binomial models, controlling for deprivation, ethnicity, age, unpaid care, council class, and year effects. To account for potential endogeneity, we ran instrumental variable regressions and dynamic panel models. Sensitivity analysis explored potential effects of funding for integrated care (the Better Care Fund). There was no consistent evidence that councils with higher per capita spend or higher social care staffing rates had lower hospital admission rates or shorter hospital stays.

D010342:Patient Acceptance of Health Care

social care
healthcare
dementia
local government expenditures


Considerations for Epidural Blood Patch and Other Postdural Puncture Headache Treatments in Patients with COVID-19.

Abstract:
BACKGROUND
A primary concern in the use of EBP in these patients is the possibility of seeding the virus in the CNS. Another important concern is related to the known hypercoagulable state in COVID-19 positive patients and associated organ dysfunction that may alter the metabolism of anticoagulants. The safety of the providers performing the EBP, the position of the patient and choices for image guidance (blind, fluoroscopic) are also key considerations to review. It is also important to explore the current state of knowledge about using allogenic instead of autologous blood as well as emerging techniques to eliminate the coronavirus from the blood.

OBJECTIVES
In this article we pose the questions of how to manage PDPH in the COVID-19 positive patient and more specifically, the use of epidural blood patch (EBP).

METHODS
Literature review.

RESULTS
EBP is usually considered after the failure of conservative and pharmacological treatments. Because of the additional risks of EBP in COVID-19 patients it is important to also consider less traditional pharmacological treatments such as theophylinnes and cosyntropin that may offer some additional benefit for COVID-19 patient. Finally, other interventions other than EBP should also be considered including occipital nerve blocks, sphenopalatine ganglion blocks (infratemporal or transnasal).

LIMITATIONS
A narrative review with paucity of literature.

CONCLUSION
Going forward, an effective treatment for COVID-19 or a safe vaccine and a deeper understanding of the pathophysiology of the virus will certainly change the risk calculus involved in performing an EBP in a COVID-19 patient.

Scemama|Pascal|P| Farah|Fadi|F| Mann|Glen|G| Margulis|Roman|R| Gritsenko|Karina|K| Shaparin|Naum|N|

epidural blood patch
PDPH
COVID 19
post dural puncture headache


Comparison of the Effectiveness of Onion Extract, Topical Steroid, and Petrolatum Emollient in Cosmetic Appearance of Upper Blepharoplasty Scar.

Abstract:
Purpose
To compare the effectiveness of onion extract, topical steroid, and petrolatum emollient in the prevention of scars in cases who underwent bilateral upper eyelid blepharoplasty.

Methods
A prospective, interventional, comparative, double-blinded case series was designed on cases who underwent upper lid blepharoplasty. After suture removal (1 week following the surgery), the eyelids of participants were randomly allocated into the three groups: The first group used onion extract on the right eyelids (n = 18), and the second group used topical steroid on the right eyelids (n = 19). In the third group, the control group, petrolatum emollient was used on the left eyelids (n = 37) of the first and second group's cases. They used drugs for 2 months and were evaluated by the Manchester Scar Scale (MSS) objectively by two graders who were blinded to the type of medication. MSS evaluates five different characteristics of the scar in addition to the Visual Analog Scale (VAS). These characteristics include color, distortion, contour, texture, and transparency. VAS scores the overall scar appearance which ranged among 0-10. The sum of the scores for the five different parameters, and VAS was calculated, analyzed, and compared among the groups.

Results
A total of 37 cases (74 eyelids) who underwent bilateral upper blepharoplasty were included. The mean ± standard deviation (SD) of age was 51.94 ± 9.26 years, 49.40 ± 9.37 years, and 47.00 ± 9.06 years in the onion extract, topical steroid, and petrolatum emollient groups, respectively (P = 0.275). There were no statistically significant differences in the mean ± SD of the sum of the MSS scores among the three groups (P = 0.924) or between the onion extract and topical steroid groups (P = 0.951). Furthermore, the color, distortion, contour, texture, transparency, and VAS scores were not statistically significantly different among the three groups or between the onion extract and topical steroid groups (P > 0.05).

Conclusion
There were no significant differences among these three groups of drugs regarding the appearance of the upper blepharoplasty scar.

Owji|Naser|N|
Khalili|Mohammad Reza|MR|
Khademi|Behzad|B|
Shirvani|Mohammad|M|
Sadati|Maryam Sadat|MS|

Onion extract
Topical steroid
Petrolatum emollient
Blepharoplasty scar


Characterization and application of poly-ferric-titanium-silicate-sulfate in disperse and reactive dye wastewaters treatment.

Abstract: A novel coagulant poly-ferric-titanium-silicate-sulfate (PFTS) was synthesized and employed to treat two typical kinds of dye wastewaters-disperse blue and reactive yellow. The results indicated that PFTS with a Si/Fe molar ratio of 0.02 exhibited superior coagulation performance, especially under alkaline condition. The residual turbidity after coagulation by PFTS was only half of that after coagulation by poly-ferric-titanium sulfate (T-PSF). The sludge volume index was also reduced by PFTS compared to T-PSF in reactive dye treatment. Through the structure and morphology investigation of PFTS, it was found that new bonds of Si-O-Fe, Si-O-Ti and Fe-OH (Si-OH) were formed, and multi-branched structures and expanded surface area were generated. Additionally, compared with T-PSF, the floc strength and the floc size were also enhanced by PFTS, which was attributed to the polymerization between polysilicic acid and Fe/Ti which formed multi-branched structures, and finally adsorption and bridging ability of the coagulant was improved. Furthermore, the floc formed in reactive yellow wastewater treatment was larger and looser than that formed in disperse blue wastewater, with poorer strength and recovery ability, which can also interpret the better coagulation efficiency in disperse dye water treatment. From the results of coagulant characterization, zeta potential and flocs properties, it can be inferred that charge neutralization by the positive charged hydrolysate of coagulant was identified as the critical effect in disperse dyes removal, while the sweep and adsorption of metal hydroxyl compound formed during the hydrolysis of coagulants were considered to play a key role in reactive dye removal.

Huang|Xin|X| Wan|Yang|Y| Shi|Baoyou|B| Shi|Jian|J| Chen|Huan|H| Liang|Huikai|H|

Dye wastewater
Coagulation
Floc properties
Hybrid coagulant


The Educational and Career Adjustment of Mexican-Origin Youth in the Context of the 2007/2008 Economic Recession.

Abstract: Youth's transition out of high school is a complex process that is informed by youth's awareness of available opportunities and resources, social norms, and social belonging and responsibility. Using a quasi-experimental design, this study examined the educational and career adjustment (i.e., college attendance status, post-secondary education type, work status, and work quality) of Mexican-origin siblings who made the transition out of high school before (i.e., 2005 or earlier) or during the economic recession (i.e., 2007 or after). Participants were 246 Mexican-origin mothers, fathers, older siblings (50% female; 38% U.S. born), and younger siblings (51% female; 47% U.S. born). Our results showed that, even though siblings grew up in similar family environments, 2007 graduates (younger siblings) were less likely to attend college, be enrolled in a university compared to a community college, and reported working in lower quality jobs as compared to 2005 graduates (older siblings). Results also showed that high economic hardship reduced the adverse association between perceived discrimination and youth educational and career adjustment, and reduced the protective effect of family obligation values on youth adjustment.

Perez-Brena|Norma J|NJ|
Wheeler|Lorey A|LA|
Rodríguez De Jesús|Sue A|SA|
Updegraff|Kimberly A|KA|
Umaña-Taylor|Adriana Y|AY|

Career
Mexican-origin
College
Family
Economic Downturn
Life Course Perspective


Multi-modal Single-Cell Analysis Reveals Brain Immune Landscape Plasticity during Aging and Gut Microbiota Dysbiosis.

Abstract: Phenotypic and functional plasticity of brain immune cells contribute to brain tissue homeostasis and disease. Immune cell plasticity is profoundly influenced by tissue microenvironment cues and systemic factors. Aging and gut microbiota dysbiosis that reshape brain immune cell plasticity and homeostasis has not been fully delineated. Using Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq), we analyze compositional and transcriptional changes of the brain immune landscape in response to aging and gut dysbiosis. Discordance between canonical surface-marker-defined immune cell types and their transcriptomes suggest transcriptional plasticity among immune cells. Ly6C+ monocytes predominate a pro-inflammatory signature in the aged brain, while innate lymphoid cells (ILCs) shift toward an ILC2-like profile. Aging increases ILC-like cells expressing a T memory stemness (Tscm) signature, which is reduced through antibiotics-induced gut dysbiosis. Systemic changes due to aging and gut dysbiosis increase propensity for neuroinflammation, providing insights into gut dysbiosis in age-related neurological diseases.

Golomb|Samantha M|SM|
Guldner|Ian H|IH|
Zhao|Anqi|A|
Wang|Qingfei|Q|
Palakurthi|Bhavana|B|
Aleksandrovic|Emilija A|EA|
Lopez|Jacqueline A|JA|
Lee|Shaun W|SW|
Yang|Kai|K|
Zhang|Siyuan|S|

brain
brain immunity
aging
gut microbiota
dysbiosis
CITE-seq
CNS
single-cell sequencing


Comparative evaluation of the extraction and analysis of urinary phospholipids and lysophospholipids using MALDI-TOF/MS.

Abstract: Lipids, particularly phospholipids (PLs) and lysophospholipids (LPLs), are attracting increasing scientific interest for their biological functions in cells and their potential as disease biomarkers for Alzheimer's disease and several types of cancer. Urinary PLs and LPLs could be ideal clinical biomarkers, because urine can be collected easily and noninvasively. However, due to their very low concentrations in urine compared with the relatively large quantity of contaminants in this matrix, efficient extraction and sensitive detection are required for analyzing urinary PLs and LPLs. In this study, various methods for analyzing PLs and LPLs in urine were compared and optimized from a clinical perspective. An optimized lipid extraction method and a matrix for matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) were established using two external ionization standards and an internal standard mix containing 13 human urinary lipids. 9-Aminoacridine (9-AA) was a useful and effective matrix for the MALDI-TOF/MS analysis of all the internal standard lipids in both positive and negative ion modes. However, it was necessary to determine the proportional lipid concentrations from the balance between the extracted lipid and the matrix. The extraction efficiency and reproducibility of the acidified Bligh and Dyer method were excellent for both positively and negatively charged lipids. Analysis of small volumes of urine was the most efficient with the 9-AA MALDI matrix at concentrations of or below 5 mM. The combined analytical procedures allowed rapid and comprehensive screening of low concentrations of PLs and LPLs in clinical samples.

Li|Xin|X| Nakayama|Kenji|K| Goto|Takayuki|T| Akamatsu|Shusuke|S| Shimizu|Koji|K| Ogawa|Osamu|O| Inoue|Takahiro|T|

D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

MALDI-TOF/MS
Lipid
Urine
Comprehensive screening
Diagnosis
Quantitative analysis


Bioconjugation of proteins with a paramagnetic NMR and fluorescent tag.

Abstract: Site-specific labeling of proteins with lanthanide ions offers great opportunities for investigating the structure, function, and dynamics of proteins by virtue of the unique properties of lanthanides. Lanthanide-tagged proteins can be studied by NMR, X-ray, fluorescence, and EPR spectroscopy. However, the rigidity of a lanthanide tag in labeling of proteins plays a key role in the determination of protein structures and interactions. Pseudocontact shift (PCS) and paramagnetic relaxation enhancement (PRE) are valuable long-range structure restraints in structural-biology NMR spectroscopy. Generation of these paramagnetic restraints generally relies on site-specific tagging of the target proteins with paramagnetic species. To avoid nonspecific interaction between the target protein and paramagnetic tag and achieve reliable paramagnetic effects, the rigidity, stability, and size of lanthanide tag is highly important in paramagnetic labeling of proteins. Here 4'-mercapto-2,2':6',2''-terpyridine-6,6''-dicarboxylic acid (4MTDA) is introduced as a a rigid paramagnetic and fluorescent tag which can be site-specifically attached to a protein by formation of a disulfide bond. 4MTDA can be readily immobilized by coordination of the protein side chain to the lanthanide ion. Large PCSs and RDCs were observed for 4MTDA-tagged proteins in complexes with paramagnetic lanthanide ions. At an excitation wavelength of 340 nm, the complex formed by protein-4MTDA and Tb(3+) produces high fluorescence with the main emission at 545 nm. These interesting features of 4MTDA make it a very promising tag that can be exploited in NMR, fluorescence, and EPR spectroscopic studies on protein structure, interaction, and dynamics.

Huang|Feng|F| Pei|Ying-Ying|YY| Zuo|Hui-Hui|HH| Chen|Jia-Liang|JL| Yang|Yin|Y| Su|Xun-Cheng|XC|

D019906:Nuclear Magnetic Resonance, Biomolecular

proteins
fluorescence
lanthanides
NMR spectroscopy
N,O ligands


Challenges in Wireless System Integration as Enablers for Indoor Context Aware Environments.

Abstract: The advent of fully interactive environments within Smart Cities and Smart Regions requires the use of multiple wireless systems. In the case of user-device interaction, which finds multiple applications such as Ambient Assisted Living, Intelligent Transportation Systems or Smart Grids, among others, large amount of transceivers are employed in order to achieve anytime, anyplace and any device connectivity. The resulting combination of heterogeneous wireless network exhibits fundamental limitations derived from Coverage/Capacity relations, as a function of required Quality of Service parameters, required bit rate, energy restrictions and adaptive modulation and coding schemes. In this context, inherent transceiver density poses challenges in overall system operation, given by multiple node operation which increases overall interference levels. In this work, a deterministic based analysis applied to variable density wireless sensor network operation within complex indoor scenarios is presented, as a function of topological node distribution. The extensive analysis derives interference characterizations, both for conventional transceivers as well as wearables, which provide relevant information in terms of individual node configuration as well as complete network layout.

López-Iturri|Peio|P|
Aguirre|Erik|E|
Azpilicueta|Leyre|L|
Astrain|José Javier|JJ|
Villandangos|Jesús|J|
Falcone|Francisco|F|

context aware environments
smart cities
smart regions
interference management
wireless sensor networks (WSN)


Method to classify elderly subjects as fallers and non-fallers based on gait energy image.

Abstract: Falls are one of the leading causes of injuries among the elderly. Therefore, distinguishing fallers and performing preventive actions is vitally important. A new variation of the gait energy image (GEI) called coloured gait energy image (CGEI) is proposed for classifying subjects as fallers and non-fallers and for visualising their gait patterns. Eight elderly fallers, eight elderly non-fallers and eight young subjects performed timed up and go (TUG) test, which is one of the well-known clinical tools for fall risk assessment and contains two gait sequences. Subjects were also asked to perform two other variations of the TUG test, namely TUG with manual load and TUG with cognitive load. Gait sequences were extracted from the TUG test based on the opinion of three human observers. Then the gait cycles were automatically extracted from the walking sequence and divided into three phases, corresponding to double support and first and second half of single support. Next, the GEI of each phase was generated and formed one of the colour components of CGEI. Histogram-based features obtained from CGEI were then used to classify the video collected from walking sequences of elderly fallers and non-fallers. Correct classification rate was improved by approximately 27% compared with the standard TUG test.

gait energy image
GEI
coloured gait energy image
CGEI
clinical tools
fall risk assessment
gait sequences
TUG test
cognitive load
gait cycles
walking sequence
colour components
histogram-based features
correct classification rate
data visualisation
elderly subject classification
gait analysis
gait pattern visualization
geriatrics
image classification
image colour analysis
image sequences
medical image processing
nonfallers
timed up and go test

P P P P P P P P P P P P P P M R M M U R M R M U R


Secreted Frizzled-Related Protein 5 Ameliorates Vascular Calcification in a Rat Model of Chronic Kidney Disease through the Wnt/β-Catenin Pathway.

Abstract:
INTRODUCTION
Vascular calcification (VC) is highly prevalent and a major cardiovascular risk factor in chronic kidney disease (CKD) patients. Secreted frizzled-related protein 5 (SFRP5), an inhibitor of the Wnt pathway, is an adipokine with a positive effect on metabolic and cardiovascular diseases. Our previous in vitro study showed that SFRP5 attenuates high phosphate-induced calcification in vascular smooth muscle cells by inhibiting the Wnt/β-catenin pathway. Therefore, we hypothesized that SFRP5 may protect against CKD-associated VC (CKD-VC) through the same signalling.

METHODS
The rat model of CKD with VC was induced by 0.75% adenine combined with 1.8% high phosphate diet, which were administered with adenovirus vectors of SFRP5. We evaluated the SFRP5 effect on VC by von Kossa staining and calcium content analysis and osteogenic markers by immunohistochemistry and Western blot. The components of Wnt/ß-catenin signalling were also evaluated.

RESULTS
SFRP5 local and serum levels were significantly decreased in the CKD-VC rat model compared with the control group. Adenovirus-mediated overexpression of SFRP5 significantly inhibited VC, which was due to suppression of CKD-induced expression of calcification and osteoblastic markers. Additionally, SFRP5 abrogated activation of the Wnt/β-catenin pathway that plays a major role in the pathogenesis of VC. The specificity of SFRP5 for inhibition of VC was confirmed using an empty adenovirus as a control.

CONCLUSION
Our results suggest that SFRP5 ameliorates VC of CKD rats by inhibiting the expression of calcification and osteoblastic markers as well as the Wnt/β-catenin pathway. Collectively, this study suggests that SFRP5 is a potential therapeutic target in CKD-VC.

Deng|Dai|D| Han|Xue|X| Diao|Zongli|Z| Liu|Wenhu|W|

Secreted frizzled-related protein 5
Vascular calcification
Chronic kidney disease
Wnt/β-catenin pathway


Self-Assembling Peptide Dendron Nanoparticles with High Stability and a Multimodal Antimicrobial Mechanism of Action.

Abstract: Self-assembling nanometer-scale structured peptide polymers and peptide dendrimers have shown promise in biomedical applications due to their versatile properties and easy availability. Herein, self-assembling peptide dendron nanoparticles (SPDNs) with potent antimicrobial activity against a range of bacteria were developed based on the nanoscale self-assembly of an arginine-proline repeat branched peptide dendron bearing a hexadecanoic acid chain. The SPDNs are biocompatible, and our most active peptide dendron nanoparticle, C16-3RP, was found to have negligible toxicity after both in vitro and in vivo studies. Furthermore, the C16-3RP nanoparticles showed excellent stability under physiological concentrations of salt ions and against serum and protease degradation, resulting in highly effective treatment in a mouse acute peritonitis model. Comprehensive analyses using a series of biofluorescence, microscopy, and transcriptome sequencing techniques revealed that C16-3RP nanoparticles kill Gram-negative bacteria by increasing bacterial membrane permeability, inducing cytoplasmic membrane depolarization and drastic membrane disruption, inhibiting ribosome biogenesis, and influencing energy generation and other processes. Collectively, C16-3RP nanoparticles show promising biocompatibility and in vivo therapeutic efficacy without apparent resistance development. These advancements may facilitate the development of peptide-based antibiotics in clinical settings.

Lai|Zhenheng|Z|0000-0002-6450-4051 Jian|Qiao|Q| Li|Guoyu|G| Shao|Changxuan|C| Zhu|Yongjie|Y| Yuan|Xiaojie|X| Chen|Hongyu|H| Shan|Anshan|A|0000-0003-2830-7509

peptide dendron
stability
mechanism of action
in vivo efficacy
self-assembling nanoparticles


Nap1l1 Controls Embryonic Neural Progenitor Cell Proliferation and Differentiation in the Developing Brain.

Abstract: The precise function and role of nucleosome assembly protein 1-like 1 (Nap1l1) in brain development are unclear. Here, we find that Nap1l1 knockdown decreases neural progenitor cell (NPC) proliferation and induces premature neuronal differentiation during cortical development. A similar deficiency in embryonic neurogenesis was observed in Nap1l1 knockout (KO) mice, which were generated using the CRISPR-Cas9 system. RNA sequencing (RNA-seq) analysis indicates that Ras-associated domain family member 10 (RassF10) may be the downstream target of Nap1l1. Furthermore, we found that Nap1l1 regulates RassF10 expression by promoting SETD1A-mediated H3K4 trimethylation at the RassF10 promoter. Nap1l1 KO defects may be rescued by RassF10 overexpression, suggesting that Nap1l1 controls NPC differentiation through RassF10. Our findings reveal an essential role for the Nap1l1 histone chaperone in cortical neurogenesis during early embryonic brain development.

Qiao|Huimin|H| Li|Yanxin|Y| Feng|Chao|C| Duo|Shuguang|S| Ji|Fen|F| Jiao|Jianwei|J|

D018507:Gene Expression Regulation, Developmental

neural differentiation and proliferation


Climate signals in tree-ring δ18 O and δ13 C from southeastern Tibet: insights from observations and forward modelling of intra- to interdecadal variability.

Abstract: Stable isotopes in tree rings are increasingly used as proxies for climatic and ecophysiological changes. However, uncertainties remain about the strength and consistency of their response to environmental variation at different temporal (i.e. seasonal to inter-decadal) scales. We developed 5 yr of intra-seasonal and 62 yr of early- and late-wood δ13 C and δ18 O series of Smith fir (Abies georgei var. smithii) on the southeastern Tibetan Plateau, and used a process-based forward model to examine the relative importance of environmental and physiological controls on the isotopic data. In this temperate high-altitude region, the response, both δ18 O and δ13 C, is primarily to variations in relative humidity, but by different processes. In δ18 O, the response is via source water δ18 O but also arises from leaf water 18 O enrichment. In δ13 C, the response is via changes in stomatal conductance but is modified by carry-over effects from prior periods. We conclude that tree-ring δ18 O may be a more robust climate proxy than δ13 C, and δ13 C may be more suited to studies of site-related physiological responses to the local environment.

Zeng|Xiaomin|X|
Liu|Xiaohong|X|
Treydte|Kerstin|K|
Evans|Michael N|MN|
Wang|Wenzhi|W|
An|Wenling|W|
Sun|Weizhen|W|
Xu|Guobao|G|
Wu|Guoju|G|
Zhang|Xuanwen|X|

tree rings
carry-over effects
earlywood
intra-seasonal patterns
latewood
southern Tibet Plateau
δ13C
δ18O


Development of Self-Healable Organic/Inorganic Hybrid Materials Containing a Biobased Copolymer via Diels-Alder Chemistry and Their Application in Electromagnetic Interference Shielding.

Abstract: In this study, a novel biobased poly(ethylene brassylate)-poly(furfuryl glycidyl ether) copolymer (PEBF) copolymer was synthesized and applied as a structure-directing template to incorporate graphene and 1,1'-(methylenedi-4,1-phenylene)bismaleimide (BMI) to fabricate a series of self-healing organic/inorganic hybrid materials. This ternary material system provided different types of diene/dienophile pairs from the furan/maleimide, graphene/furan, and graphene/maleimide combinations to build a crosslinked network via multiple Diels-Alder (DA) reactions and synergistically co-assembled graphene sheets into the polymeric matrix with a uniform dispersibility. The PEBF/graphene/BMI hybrid system possessed an efficient self-repairability for healing structural defects and an electromagnetic interference shielding ability in the Ku-band frequency range. We believe that the development of the biobased self-healing hybrid system provides a promising direction for the creation of a new class of materials with the advantages of environmental friendliness as well as durability, and shows potential for use in advanced electromagnetic applications.

Lee|Yi-Huan|YH| Ko|Wen-Chi|WC| Zhuang|Yan-Nian|YN| Wang|Lu-Ying|LY| Yu|Tao-Wei|TW| Lee|Shaio-Yen|SY| Way|Tun-Fun|TF| Rwei|Syang-Peng|SP|0000-0001-6169-5852

self-healing
organic/inorganic hybrid materials
biobased copolymer
electromagnetic interference shielding
Diels–Alder chemistry


Examining the high rate of cigarette smoking among adults with a GED.

Abstract:
OBJECTIVES
We seek to identify characteristics of GED holders that explain their very high smoking rates compared with high school (HS) graduates.

METHODS
We pooled data from the 2006-2014 National Health Interview Surveys (NHIS) for adults aged 25 and older (n=235,031) to describe cigarette smoking behaviors and smoking history for adults in six education categories, with a focus on comparing GED holders to HS graduates. Logistic regression was used to predict the odds of current cigarette smoking and successful quitting, accounting for demographic, employment, family/sociocultural, mental health, and other potential confounders.

RESULTS
The smoking rate among adults with a GED (44.1%) was more than five times the rate for those with a college degree (8.3%) and almost twice the rate of adults whose highest level of education was a high school diploma (23.6%). GED holders were also more likely to have started smoking before the age of 15 (32.2%) compared with HS graduates (12.2%) (p<0.001). Even after controlling for 23 socio-demographic and health characteristics, GED holders retained significantly higher odds of current smoking compared to HS graduates (OR=1.73; 95% CI: 1.56, 1.93) and significantly lower odds of successful quitting (OR=0.83, 95% CI: 0.73, 0.94).

CONCLUSIONS
GED holders had greater odds of being a current cigarette smoker, regardless of other characteristics that usually explain smoking. Earlier smoking initiation among GED holders, in combination with lower odds of quitting, contributed to their higher current smoking rate.

Schoenborn|Charlotte A|CA|
Stommel|Manfred|M|
Lucas|Jacqueline W|JW|


Validation of the Korean version of the Boston Autonomic Symptom Questionnaire.

Abstract:
BACKGROUND AND PURPOSE
The Boston Autonomic Symptom Questionnaire (BASQ) is a quantitative tool using a numeric rating scale to assess the symptoms of systemic dysautonomia, including cardiovascular, gastrointestinal, urinary, sudomotor, vasomotor, and sexual functions. The aim of this study was to validate the Korean version of the BASQ (KBASQ).

METHODS
Prospectively enrolled subjects who submitted to autonomic function tests, including tests for cardiovagal, adrenergic, and sudomotor functions, also completed the KBASQ and the Korean version of the Orthostatic Grading Scale (KOGS), a validated questionnaire or assessing orthostatic symptoms.Twenty-eight subjects completed the KBASQ twice to assess test-retest reliability. We classified the subjects to dysautonomia or normal control group according to dysautonomic symptoms and the results of autonomic function tests.

RESULTS
This study enrolled 225 subjects aged 54.0±18.1 years (mean±standard deviation), with a male/female ratio of 1/1.03. The internal validity of the KBASQ was excellent (Cronbach's α=0.922), and that of each of its subscales ranged from excellent to acceptable (Cronbach's α=0.709-0.952). The test-retest reliability was good, with correlation coefficients ranging from 0.354 to 0.917. The subcategory scores for the KBASQ were significantly higher in the dysautonomia group than in the normal control group. There were significant correlations among the items in the KBASQ and KOGS. There was also a significant correlation between KBASQ scores and the results of the autonomic function tests.

CONCLUSIONS
The internal validity and reliability of the KBASQ were good, indicating that it may be a useful screening tool for the systematic evaluation of autonomic symptoms in patients with dysautonomia.

symptoms
questionnaire
autonomic nervous system
reliability and validity
validation study


Sensory neuronopathies.

Abstract: The sensory neuronopathies (or ganglionopathies) are a small subcategory of neuropathies characterized by primary degeneration of the dorsal root ganglia and trigeminal ganglion sensory neurons, resulting in a distinctive clinical presentation. Patients typically have subacute onset of asymmetric, non-length-dependent sensory impairment and early ataxia. The etiologies of acquired sensory neuronopathies are rather limited. Early identification is imperative, as they may herald an underlying malignancy or an autoimmune condition such as Sjögren syndrome. This review addresses the various causes of acquired sensory neuronopathies, the recommended diagnostic approach, and treatment options. Finally, I will briefly discuss a select few hereditary and degenerative sensory neuronopathies, which, in contrast to the acquired disorders, are slowly progressive and are usually associated with additional neurological symptoms.

D010523:Peripheral Nervous System Diseases

sensory neuronopathy
Sjögren syndrome
dorsal root ganglion
paraneoplastic neuropathy
sensory ganglionopathy


Self-compassion: a resource for positive aging.

Abstract:
OBJECTIVES
Self-compassion has been associated with psychological health in young and multigenerational samples. This study investigated whether self-compassion may be associated with subjective well-being (positive affect [PA] and negative affect [NA]) and psychological well-being (ego integrity and meaning in life) in older adults. It also assessed the structure of the Self-Compassion Scale (SCS; Neff, 2003a) in older adults.

METHOD
A total of 185 adults aged 65 and older (M age = 73.42) completed several self-report measures, including the SCS.

RESULTS
Path analysis revealed that self-compassion was significantly positively associated with PA, ego integrity, and meaning in life, and negatively associated with NA. Factor analyses indicated that the SCS structure identified among undergraduates was not observed in our older sample. Instead, two factors emerged which provided predictive utility.

DISCUSSION
These results extend research knowledge, inform strategies to enhance well-being in older adults, and indicate that self-compassion may represent a valuable psychological resource for positive aging.

Phillips|Wendy J|WJ|
Ferguson|Susan J|SJ|

Self-Compassion
Aging
Psychological well-being
Subjective well-being.


Snai1 represses Nanog to promote embryonic stem cell differentiation.

Abstract: Embryonic stem cell (ESC) self-renewal and pluripotency is maintained by an external signaling pathways and intrinsic regulatory networks involving ESC-specific transcriptional complexes (mainly formed by OCT3/4, Sox2 and Nanog proteins), the Polycomb repressive complex 2 (PRC2) and DNA methylation [1-8]. Among these, Nanog represents the more ESC specific factor and its repression correlates with the loss of pluripotency and ESC differentiation [9-11]. During ESC early differentiation, many development-associated genes become upregulated and although, in general, much is known about the pluripotency self-renewal circuitry, the molecular events that lead ESCs to exit from pluripotency and begin differentiation are largely unknown. Snai1 is one the most early induced genes during ESC differentiation in vitro and in vivo [12,13]. Here we show that Snai1 is able to directly repress several stemness-associated genes including Nanog. We use a ESC stable-line expressing a inducible Snai1 protein. We here show microarray analysis of embryonic stem cells (ESC) expressing Snail-ER at various time points of induction with 4-OH. Data were deposited in Gene Expression Omnibus (GEO) datasets under reference GSE57854 and here: http://epigenetics.hugef-research.org/data.php.

Snai1
Nanog
Embryonic stem cells
Microarray
Pluripotency exit


The relationship between preoperative T helper cytokines in the ileal mucosa and the pathogenesis of pouchitis.

Abstract:
BACKGROUND
Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed.

AIM
To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction.

METHODS
This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined.

RESULTS
Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03).

CONCLUSION
IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Cytokine
Pouchitis
IBD
Ulcerative colitis
IFN-γ


Aberrant accrual of BIN1 near Alzheimer's disease amyloid deposits in transgenic models.

Abstract: Bridging integrator 1 (BIN1) is the most significant late-onset Alzheimer's disease (AD) susceptibility locus identified via genome-wide association studies. BIN1 is an adaptor protein that regulates membrane dynamics in the context of endocytosis and membrane remodeling. An increase in BIN1 expression and changes in the relative levels of alternatively spliced BIN1 isoforms have been reported in the brains of patients with AD. BIN1 can bind to Tau, and an increase in BIN1 expression correlates with Tau pathology. In contrast, the loss of BIN1 expression in cultured cells elevates Aβ production and Tau propagation by insfluencing endocytosis and recycling. Here, we show that BIN1 accumulates adjacent to amyloid deposits in vivo. We found an increase in insoluble BIN1 and a striking accrual of BIN1 within and near amyloid deposits in the brains of multiple transgenic models of AD. The peri-deposit aberrant BIN1 localization was conspicuously different from the accumulation of APP and BACE1 within dystrophic neurites. Although BIN1 is highly expressed in mature oligodendrocytes, BIN1 association with amyloid deposits occurred in the absence of the accretion of other oligodendrocyte or myelin proteins. Finally, super-resolution microscopy and immunogold electron microscopy analyses highlight the presence of BIN1 in proximity to amyloid fibrils at the edges of amyloid deposits. These results reveal the aberrant accumulation of BIN1 is a feature associated with AD amyloid pathology. Our findings suggest a potential role for BIN1 in extracellular Aβ deposition in vivo that is distinct from its well-characterized function as an adaptor protein in endocytosis and membrane remodeling.

De Rossi|Pierre|P|0000-0002-2356-4269
Andrew|Robert J|RJ|0000-0001-5773-6404
Musial|Timothy F|TF|0000-0003-0533-7967
Buggia-Prevot|Virginie|V|
Xu|Guilian|G|
Ponnusamy|Moorthi|M|
Ly|Han|H|
Krause|Sofia V|SV|
Rice|Richard C|RC|
de l'Estoile|Valentine|V|
Valin|Tess|T|
Salem|Someya|S|
Despa|Florin|F|
Borchelt|David R|DR|
Bindokas|Vytas P|VP|
Nicholson|Daniel A|DA|
Thinakaran|Gopal|G|0000-0001-5523-6780

D048868:Adaptor Proteins, Signal Transducing

BIN1
Alzheimer's disease
amyloid
GWAS
LOAD
senile plaque


Advanced Matrixes for Binder-Free Nanostructured Electrodes in Lithium-Ion Batteries.

Abstract: Commercial lithium-ion batteries (LIBs), limited by their insufficient reversible capacity, short cyclability, and high cost, are facing ever-growing requirements for further increases in power capability, energy density, lifespan, and flexibility. The presence of insulating and electrochemically inactive binders in commercial LIB electrodes causes uneven active material distribution and poor contact of these materials with substrates, reducing battery performance. Thus, nanostructured electrodes with binder-free designs are developed and have numerous advantages including large surface area, robust adhesion to substrates, high areal/specific capacity, fast electron/ion transfer, and free space for alleviating volume expansion, leading to superior battery performance. Herein, recent progress on different kinds of supporting matrixes including metals, carbonaceous materials, and polymers as well as other substrates for binder-free nanostructured electrodes in LIBs are summarized systematically. Furthermore, the potential applications of these binder-free nanostructured electrodes in practical full-cell-configuration LIBs, in particular fully flexible/stretchable LIBs, are outlined in detail. Finally, the future opportunities and challenges for such full-cell LIBs based on binder-free nanostructured electrodes are discussed.

matrixes
nanostructures
electrodes
lithium-ion batteries