Microwave-assisted recovery of monomeric sugars from an acidic steam treated wood hydrolysate.

Abstract: Fractionation of components from bio-refinery wastes streams is complicated by the presence of both oligomer and lignin fractions. Microwave-assisted acid hydrolysis was used in this study to convert oligomer sugars in an industrial prehydrolysis liquor (PHL) to monomeric sugars. A total of 19.6 g/L monomeric sugars was obtained at a combined severity factor (CSF) of 3.2. Furthermore, it was found that xylan linked to lignin in a lignin-carbohydrate complex (LCC) could be liberated, resulting in lignin with a relatively low dispersity (3.12) and average molecular weight (1718 g/mol) that has high commercial value in the phenol-formaldehyde resin industry. This study presents for the first time a relatively inexpensive method for recovery of 100% of available sugars in the PHL without apparent loss in monomeric sugar as well as 50% removal of lignin as a valuable by-product. Application of this method can significantly improve the economic sustainability of forest-based biorefineries.


Heparin-induced thrombocytopenia in a non-heparin-naive patient: a case report.

Abstract:
INTRODUCTION
Administration of low molecular weight heparin (LMWH) is recommended for prophylaxis of venous thromboembolism in patients undergoing hip surgery. In this context, heparin-induced thrombocytopenia (HIT) type II is a complication of rare incidence but sometimes fatal outcome.

CASE DESCRIPTION
A 52-year old obese patient undergoing antithrombotic therapy with Enoxaparin after hip surgery presented with a painful, swollen leg and thrombocytopenia on day eight after surgery. Medical history showed previous administration of Enoxaparin without complications 2 years ago. Further diagnostic investigation supplied evidence of multiple thromboembolic events and concomitant compartment syndrome. Administration of Enoxaparin was stopped immediately and treatment with Argatroban was initiated. Diagnosis of HIT was confirmed according to current guidelines. Despite interventional thrombectomy and fasciotomy, amputation of both lower limbs had to be performed due to ongoing necroses. After a 30-days-stay at the intensive care unit because of sepsis, respiratory and renal failure, clinical condition improved and the patient could be transferred for rehabilitation.

DISCUSSION AND EVALUATION
HIT II is known as complication of administration of LMWH in the perioperative setting. Diagnosis results from clinical findings and platelet count. Argatroban is recommended as an alternative therapeutic anticoagulant in HIT II. Inflammation and surgical trauma are discussed as priming factors to increase risk of HIT II.

CONCLUSIONS
Administration of LMWH may result in HIT II despite prior uneventful drug exposure. Except for immediate diagnosis, only consequent anticoagulation can stop the course of disease. Hence, interdisciplinary awareness is inevitable for early diagnosis and accurate therapy to prevent from a catastrophic clinical course.

Wiegele|Marion|M| Adelmann|Dieter|D| Gratz|Johannes|J| Schaden|Eva|E|

LMWH
Argatroban
HIT II
Heparin induced thrombocytopenia
Low molecular heparin


Stegomyia Indices and Risk of Dengue Transmission: A Lack of Correlation.

Abstract: Dengue is present in 128 countries worldwide and is still expanding. There is currently no treatment or universally approved vaccine available. Therefore, prevention and control of mosquito vectors remain the most efficient ways of managing the risk of dengue outbreaks. The Stegomyia indices have been developed as quantitative indicators of the risk of dengue outbreaks. However, conflictual data are circulating about their reliability. We report in this article the first extensive study on Stegomyia indices, covering 78 locations of differing environmental and socio-economic conditions, climate, and population density across Indonesia, from West Sumatra to Papua. A total of 65,876 mosquito larvae and pupae were collected for the study. A correlation was found between incidence and human population density. No correlation was found between the incidence of dengue and the Stegomyia indices.

Garjito|Triwibowo Ambar|TA|
Hidajat|Muhammad Choirul|MC|
Kinansi|Revi Rosavika|RR|
Setyaningsih|Riyani|R|
Anggraeni|Yusnita Mirna|YM|
Mujiyanto|||
Trapsilowati|Wiwik|W|
Jastal|||
Ristiyanto|||
Satoto|Tri Baskoro Tunggul|TBT|
Gavotte|Laurent|L|
Manguin|Sylvie|S|
Frutos|Roger|R|

Stegomyia indices
dengue
incidence
Aedes aegypti
Aedes albopictus
mosquito-borne disease


Rcn3 Suppression Was Responsible for Partial Relief of Emphysema as Shown by Specific Type II Alveolar Epithelial Cell Rcn3 CKO Mouse Model.

Abstract:
Background
Chronic obstructive pulmonary disease (COPD), characterized by irreversible airflow limitation, is a highly prevalent lung disease worldwide and imposes increasing disease burdens globally. Emphysema is one of the primary pathological features contributing to the irreversible decline of pulmonary function in COPD patients, but the pathogenetic mechanisms remain unclear. Reticulocalbin 3 (Rcn3) is an endoplasmic reticulum (ER) lumen protein localized in the secretory pathway of living cells. Rcn3 in type II alveolar epithelial cell (AECIIs) has been reported to play a critical role in regulating perinatal lung development and bleomycin-induced lung injury-repair processes. We hypothesized that Rcn3 deficiency is associated with the development of emphysema during COPD, which is associated with the dysfunction of injury-repair modulated by alveolar epithelial cells.

Materials and Methods
We examined Rcn3 expression in lung specimens from COPD patients and non-COPD control patients undergoing lung lobectomy or pneumonectomy. Two mouse models of emphysema were established by cigarette smoke (CS) exposure and intratracheal instillation of porcine pancreatic elastase (PPE). Rcn3 expression was detected in the lung tissues from these mice. Furthermore, conditional knockout (CKO) mice with Rcn3 deletion specific to AECIIs were used to explore the role of Rcn3 in PPE-induced emphysema progression. Rcn3 protein expression in lung tissues was evaluated by Western blot and immunohistochemistry. Rcn3 mRNA expression in lung tissues was detected by qPCR.

Results
Rcn3 expression was significantly increased in the lung specimens from COPD patients versus non-COPD patients and the level of Rcn3 increase was associated with the degree of emphysema. Rcn3 expression were also significantly up-regulated in both CS-induced and PPE-induced emphysematous mouse lungs. Moreover, the selective ablation of Rcn3 in AECIIs significantly alleviated severity of the mouse emphysema in response to intratracheal installation of PPE.

Conclusion
Our data, for the first time, indicated that suppression of Rcn3 expression in AECIIs has a beneficial effect on PPE-induced emphysema.

Zhang|Qianyu|Q|
Wang|Tong|T|
Jin|Jiawei|J|
Shi|Xiaoqian|X|
Huang|Aiben|A|
Ma|Zhenru|Z|
Li|Jiujie|J|
Wang|Shiyu|S|
Z Ma|Runlin|R|0000-0003-4422-6039
Fang|Qiuhong|Q|

D029424:Pulmonary Disease, Chronic Obstructive

Rcn3
emphysema
type II alveolar epithelial cell
COPD


Epigallocatechin gallate from green tea effectively blocks infection of SARS-CoV-2 and new variants by inhibiting spike binding to ACE2 receptor.

Abstract:
BACKGROUND
As the COVID-19 pandemic rages on, the new SARS-CoV-2 variants have emerged in the different regions of the world. These newly emerged variants have mutations in their spike (S) protein that may confer resistance to vaccine-elicited immunity and existing neutralizing antibody therapeutics. Therefore, there is still an urgent need of safe, effective, and affordable agents for prevention/treatment of SARS-CoV-2 and its variant infection.

RESULTS
We demonstrated that green tea beverage (GTB) or its major ingredient, epigallocatechin gallate (EGCG), were highly effective in inhibiting infection of live SARS-CoV-2 and human coronavirus (HCoV OC43). In addition, infection of the pseudoviruses with spikes of the new variants (UK-B.1.1.7, SA-B.1.351, and CA-B.1.429) was efficiently blocked by GTB or EGCG. Among the 4 active green tea catechins at noncytotoxic doses, EGCG was the most potent in the action against the viruses. The highest inhibitory activity was observed when the viruses or the cells were pre-incubated with EGCG prior to the infection. Mechanistic studies revealed that EGCG blocked infection at the entry step through interfering with the engagement of the receptor binding domain (RBD) of the viral spikes to angiotensin-converting enzyme 2 (ACE2) receptor of the host cells.

CONCLUSIONS
These data support further clinical evaluation and development of EGCG as a novel, safe, and cost-effective natural product for prevention/treatment of SARS-CoV-2 transmission and infection.

Epigallocatechin gallate
Green tea
Variants
Receptor binding domain
SASR-CoV-2


How Health Care Professionals Evaluate a Digital Intervention to Improve Medication Adherence: Qualitative Exploratory Study.

Abstract:
BACKGROUND
Medication nonadherence poses a serious and a hard-to-tackle problem for many chronic diseases. Electronic health (eHealth) apps that foster patient engagement and shared decision making (SDM) may be a novel approach to improve medication adherence.

OBJECTIVE
The aim of this study was to investigate the perspective of health care professionals regarding a newly developed digital app aimed to improve medication adherence. Familial hypercholesterolemia (FH) was chosen as a case example.

METHODS
A Web-based prototype of the eHealth app-MIK-was codesigned with patients and health care professionals. After user tests with patients, we performed semistructured interviews and user tests with 12 physicians from 6 different hospitals to examine how the functionalities offered by MIK could assist physicians in their consultation and how they could be integrated into daily clinical practice. Qualitative thematic analysis was used to identify themes that covered the physicians' evaluations.

RESULTS
On the basis of the interview data, 3 themes were identified, which were (1) perceived impact on patient-physician collaboration; (2) perceived impact on the patient's understanding and self-management regarding medication adherence; and (3) perceived impact on clinical decisions and workflow.

CONCLUSIONS
The eHealth app MIK seems to have the potential to improve the consultation between the patient and the physician in terms of collaboration and patient engagement. The impact of eHealth apps based on the concept of SDM for improving medication-taking behavior and clinical outcomes is yet to be evaluated. Insights will be useful for further development of eHealth apps aimed at improving self-management by means of patient engagement and SDM.

medication adherence
eHealth
patient engagement
shared decision making
self-management


The Evolution of Antimicrobial Resistance in Mexico During the Last Decade: Results from the INVIFAR Group.

Abstract: Surveillance of antimicrobial resistance (AMR) requires an international approach with national and local strategies. Our aim was to summarize a retrospective 10-year report of antibiotic resistance of gram-positive and gram-negative bacteria in Mexico.  A total of 46 centers from 22 states of Mexico participated. Databases of AMR from January 2009 to December 2018 were included for most species. The 10-year period was divided into five 2-year periods.  For Staphylococcus aureus, a decrease in resistance in all specimens was observed for erythromycin and oxacillin (p < 0.0001 for each). For Enterobacter spp., resistance to meropenem increased for urine specimens (p = 0.0042). For Klebsiella spp., increased drug resistance in specimens collected from blood was observed for trimethoprim/sulfamethoxazole, gentamicin, tobramycin (p < 0.0001 for each), meropenem (p = 0.0014), and aztreonam (p = 0.0030). For Acinetobacter baumannii complex, high drug resistance was detected for almost all antibiotics, including carbapenems, except for tobramycin, which showed decreased resistance for urine, respiratory, and blood isolates (p < 0.0001 for each), and for amikacin, which showed a decrease in resistance in urine specimens (p = 0.0002). An increase in resistance to cefepime was found for urine, respiratory, and blood specimens (p < 0.0001 for each). For Pseudomonas aeruginosa, aztreonam resistance increased for isolates recovered from blood (p = 0.0001).  This laboratory-based surveillance of antibiotic resistance shows that resistance is increasing for some antibiotics in different bacterial species in Mexico and highlights the need for continuous monitoring of antibiotic resistance.

antimicrobial resistance
resistance
Mexico
INVIFAR
Enterobacteriaceae
epidemiology data


Effect of Flavonoid-Rich Extract of Glycyrrhiza glabra on Gut-Friendly Microorganisms, Commercial Probiotic Preparations, and Digestive Enzymes.

Abstract: Flavonoid-rich extract prepared from Glycyrrhiza glabra has been found to be beneficial in patients with functional dyspepsia and was reported to possess some gut health-promoting properties such as antioxidant, anti-inflammatory and anti-Helicobacter pylori activities. In the present study, the flavonoid-rich extract of Glycyrrhiza glabra was evaluated for its compatibility with probiotic strains (Lactobacillus casei, Lactobacillus fermentum, Lactobacillus plantarum, and Streptococcus thermophilus), commercial probiotic drinks, and digestive enzymes (pancreatic α-amylase, α-glucosidase, phytase, xylanase, and pancreatic lipase). Results of this study indicated that the flavonoid-rich extract of Glycyrrhiza glabra is compatible with the tested probiotic strains, probiotic drinks and digestive enzymes.

Asha|Mannanthendil Kumaran|MK|
Debraj|Debnath|D|
Dethe|Shekhar|S|
Bhaskar|Anirban|A|
Muruganantham|Nithyanantham|N|
Deepak|Mundkinajeddu|M|

Glycyrrhiza glabra
probiotics
digestive enzymes
gut health


Filling the gaps between theory and daily clinical procedural skills training in family medicine.

Abstract: Performance of procedures is an integral part of any family physician/general practitioner's practice. Unfortunately, discrepancy occurs between the existing theoretical methods of procedural teaching and the training imparted during real daily practice, which creates gaps that need to be overcome. This article identifies and reviews teaching gaps in family medicine training and presents suggestions to overcome them with a view to forming holistic psychomotor skills based on the learner's characteristics within the patient-centred philosophy of family medicine.

D002983:Clinical Competence
D003479:Curriculum
D005194:Family Practice
D006801:Humans
D007396:Internship and Residency
D011597:Psychomotor Performance
D013514:Surgical Procedures, Operative

Procedural skills
procedures
family medicine
teaching
psychomotor skills
general practice
minor surgery


Depsidone Derivatives and a Cyclopeptide Produced by Marine Fungus Aspergillus unguis under Chemical Induction and by Its Plasma Induced Mutant.

Abstract: A new depsidone derivative (1), aspergillusidone G, was isolated from a marine fungus Aspergillus unguis, together with eight known depsidones (2‒9) and a cyclic peptide (10): agonodepside A (2), nornidulin (3), nidulin (4), aspergillusidone F (5), unguinol (6), aspergillusidone C (7), 2-chlorounguinol (8), aspergillusidone A (9), and unguisin A (10). Compounds 1‒4 and 7‒9 were obtained from the plasma induced mutant of this fungus, while 5, 6, and 10 were isolated from the original strain under chemical induction. Their structures were identified using spectroscopic analysis, as well as by comparison with literature data. The HPLC fingerprint analysis indicates that chemical induction and plasma mutagenesis effectively influenced the secondary metabolism, which may be due to their regulation in the key steps in depsidone biosynthesis. In bioassays, compound 9 inhibited acetylcholinesterase (AChE) with IC50 in 56.75 μM. Compounds 1, 5, 7, 8, and 9 showed moderate to strong activity towards different microbes. Compounds 3, 4, and 5 exhibited potent larvicidality against brine shrimp. In docking studies, higher negative CDOCKER interaction energy and richer strong interactions between AChE and 9 explained the greater activity of 9 compared to 1. Chemical induction and plasma mutagenesis can be used as tools to expand the chemodiversity of fungi and obtain useful natural products.

Yang|Wen-Cong|WC|0000-0001-5127-0332 Bao|Hai-Yan|HY| Liu|Ya-Yue|YY| Nie|Ying-Ying|YY| Yang|Jing-Ming|JM| Hong|Peng-Zhi|PZ| Zhang|Yi|Y|0000-0002-1600-7456

D000110:Acetylcholinesterase
D000890:Anti-Infective Agents
D001230:Aspergillus
D002176:Candida albicans
D002800:Cholinesterase Inhibitors
D053630:Depsides
D008826:Microbial Sensitivity Tests
D008958:Models, Molecular
D062105:Molecular Docking Simulation
D015394:Molecular Structure
D009154:Mutation
D010456:Peptides, Cyclic
D058626:Plasma Gases
D064210:Secondary Metabolism
D013211:Staphylococcus aureus
D014736:Vibrio parahaemolyticus

depsidones
Aspergillus unguis
chemical induction
docking
plasma-induced mutant


Putting underspecification in context: ERP evidence for sparse representations in morphophonological alternations.

Abstract: Numerous studies have shown evidence for a sparse lexicon in speech perception, often in the guise of underspecification, where certain information is omitted in the specification of phonological forms. While previous work has made a good case for underspecifying certain features of single speech sounds, the role of phonological context in underspecification has been overlooked. Contextually-mediated underspecification is particularly relevant to conceptualizations of the lexicon, as it is couched in item-specific (as opposed to phoneme-specific) patterning. In this study, we present behavioral and ERP evidence that surrounding phonological context may trigger underspecified lexical forms, using regular morphophonological alternations in English.

Underspecification
phonological context
LAN
phonological alternation
prefix processing


Loving myself through thick and thin: Appearance contingent self-worth, gendered racial microaggressions and African American women's body appreciation.

Abstract: Contrary to previous literature, recent studies have indicated that African American women are reporting similar rates of body dissatisfaction as their European American counterparts. Yet, little is known about contextual factors, such as gendered racial microaggressions and their association with body appreciation, and whether appearance contingent self-worth accounts for this relationship. Consistent with intersectionality theory, this study examined appearance-contingent self-worth as a mediator between stress related to experiencing sexually objectifying gendered racial microaggressions and body appreciation. African American emerging adult women (N = 143), predominately from the Southern United States, completed a self-report measure of gendered racial microaggressions, appearance contingent self-worth, and body appreciation. Results demonstrated that appearance contingent self-worth, at least in part, mediated the relationship between stress related to gendered racial microaggressions and African American women's appreciation for their bodies. It is imperative future body image interventions aimed at African American emerging adult women address factors, such as appearance contingent self-worth and gendered racial microaggressions, in their efforts improve body appreciation.

Dunn|Chelsie E|CE|
Hood|Kristina B|KB|
Owens|Bianca D|BD|

Appearance contingent self-worth
Gendered racial microaggression
African American women
Body appreciation
Intersectionality theory
Sexual objectification


Radiogenomics in brain, breast, and lung cancer: opportunities and challenges.

Abstract: The field of radiogenomics largely focuses on developing imaging surrogates for genomic signatures and integrating imaging, genomic, and molecular data to develop combined personalized biomarkers for characterizing various diseases. Our study aims to highlight the current state-of-the-art and the role of radiogenomics in cancer research, focusing mainly on solid tumors, and is broadly divided into four sections. The first section reviews representative studies that establish the biologic basis of radiomic signatures using gene expression and molecular profiling information. The second section includes studies that aim to non-invasively predict molecular subtypes of tumors using radiomic signatures. The third section reviews studies that evaluate the potential to augment the performance of established prognostic signatures by combining complementary information encoded by radiomic and genomic signatures derived from cancer tumors. The fourth section includes studies that focus on ascertaining the biological significance of radiomic phenotypes. We conclude by discussing current challenges and opportunities in the field, such as the importance of coordination between imaging device manufacturers, regulatory organizations, health care providers, pharmaceutical companies, academic institutions, and physicians for the effective standardization of the results from radiogenomic signatures and for the potential use of these findings to improve precision care for cancer patients.

radiogenomics
cancer research
prognostic signatures
precision medicine


A Newly Discovered Phenylethanoid Glycoside from Stevia rebaudiana Bertoni Affects Insulin Secretion in Rat INS-1 Islet β Cells.

Abstract: The tea-like beverage Stevia rebaudiana Bertoni (Stevia) is popular in China because it reduces blood glucose and has a sweet taste. In this work, a comprehensive quality assessment of Stevia led to the discovery of five phenylethanoid glycosides, namely steviophethanoside (1), cuchiloside (2), salidroside (3), icariside D (4), and tyrosol (5). Of them, compound 1 is a novel compound. Mass spectrometry and NMR spectroscopy were employed to confirm the absolute configuration. A hydrolytic step with 4 N TFA at 95 °C for 4 h was used to confirm the monosaccharides. In addition, Discovery Studio 4.0 was used to predict the ADME and toxicity activity of compound 1. The results suggested that compound 1 was biocompatible and had poor toxicity, which was verified by rat INS-1 islet β cells through an MTT assay. Meanwhile, a significant stimulatory effect on INS-1 cells was observed, which indicated a hypoglycemic effect of compound 1. This is the first report that describes a natural, novel, and hypoglycemic phenylethanoid glycoside in Stevia.

He|Jing|J| Zhu|Nai-Liang|NL|0000-0001-7488-1291 Kong|Jing|J| Peng|Ping|P| Li|Lin-Fu|LF| Wei|Xiao-Lu|XL| Jiang|Yan-Yan|YY| Zhang|Yan-Ling|YL| Bian|Bao-Lin|BL| She|Gai-Mei|GM|0000-0003-1754-2140 Shi|Ren-Bing|RB|

phenylethanoid glycoside
Stevia rebaudiana Bertoni
insulin secretion
DS
structure


Influence of the Coach's Method and Leadership Profile on the Positive Development of Young Players in Team Sports.

Abstract: In a time of instability caused by adolescence, sport may represent a resource to prevent future individual and social problems. Within the complex relationships developed in social sports contexts, the figure of the coach can be fundamental for the development of a beneficial environment. The objective of the research was to investigate the relationship between the teaching methods and leadership profile of the coach and outcomes on the perception of positive development of young people participating in an after school sports program. In total participated, 910 adolescents (14.0 ± 1.8 years) and 57 coaches (45.57 ± 7.25 years) in 37 public schools in the city of Curitiba, in the state of Paraná-Brazil. Ordinal logistic regression was used to verify the independent associations between the variables sex, category, sport, trainer methodology, perception of the coaches, and perception of the athletes with the tertiles of the scores of each developmental characteristic of the young athletes (personal and social skills, cognitive skills, goal setting, and initiative). Odds ratios (OR) were obtained with a 95% confidence interval (95%CI), adopting p < 0.05. The small sized games method were positively associated with cognitive skills and goal setting. Positive associations were also found between athletes' perceptions of the leadership profile of coaches with: personal and social skills (instructor, democratic behaviour, social support, and positive feedback), cognitive skills (instructor, democratic behaviour, and social support), goal setting (instructor, social support, and positive feedback), and initiative (instructor and positive feedback). In addition, the athletes' perception of the coaches' autocratic behaviour was inversely associated with personal and social skills and goal setting. For the evaluated program, the results suggest the choice, on the part of the coaches, of small sized games, combined with a democratic, affective, motivating leadership profile that provides instructions on technical skills and game strategies. The combination of the designated psych-pedagogical aspects is correlated to the positive development of young people through team sports.

de Albuquerque|Luis Rogério|LR|
Scheeren|Eduardo Mendonça|EM|
Vagetti|Gislaine Cristina|GC|
de Oliveira|Valdomiro|V|

leadership
team sports
Teaching methods
positive youth development


Exchange of organohalogen compounds between air and tree bark in the Yellow River region.

Abstract: Organohalogen compound concentrations in paired air and bark samples from the Yellow River region were determined. Overall, the organohalogen compound concentrations were higher in the samples from the lower than from the upper Yellow River region. The polybrominated diphenyl ether, polychlorinated biphenyl, and organochlorine pesticide concentrations were 310-5200, 0.92-3.8, and 120-6700 pg m(-3), respectively, in the air samples and 29,000-190,0000, 220-1400, and 49,000-220,0000 pg g(-1) lipid weight, respectively, in the bark samples. The concentrations in the air samples were significantly positively correlated with the concentrations in the bark samples. Constant B, related to the partitioning of a contaminant between the gas and particle phases in the air, was calculated for each compound. This was the first time constant B was simultaneously been determined for a range of different organohalogen compounds. An air-tree bark exchange model was calibrated and verified. The exchange coefficients (K(BA)) that were determined were compared with the model results, and the optimum K(OA) values for use in the model were found to be 10(9)-10(16). The compound of interest needed to be detected in more than 50% of the samples for the model results to be valid.

He|Chang|C| Jin|Jun|J| Li|Guangyao|G| Wang|Ying|Y|

D000393:Air Pollutants
D002681:China
D004784:Environmental Monitoring
D055768:Halogenated Diphenyl Ethers
D006843:Hydrocarbons, Chlorinated
D008962:Models, Theoretical
D010575:Pesticides
D024301:Plant Bark
D011078:Polychlorinated Biphenyls
D045483:Rivers

Tree bark
Brominated flame retardants (BFRs)
Passive air sampler (PAS)
Persistent organic pollutants (POPs)


Evaluation of soluble concentration Fas and Fas ligand in maternal and cord blood 3rd trimester of pregnancy.

Abstract:
OBJECTIVES
The the study was to estimate the concentrations of antiapoptotic sFas and pro-apoptotic FasL in the serum of pregnant women in the third trimester of pregnancy and in the cord blood serum of neonates from vein and arteries separately. The correlation could be crucial for evaluation of apoptosis process intensity in placenta and the role of fetal blood circulation system on distribution of sFas and FasL.

MATERIAL AND METHODS
The study group consisted of 28 pregnant women in physiological pregnancy, between 38- 41 weeks. Vein blood was taken from maternal elbow vein and umbilical cord, separately from vein and arteries. The research was done by sets for sFas and FasL from R&D Systems Elisa kit.

RESULTS
In arterial and vein cord blood there were much more lower concentrations of sFas than in maternal blood-arterial cord blood 3351.78 pg/mL, vein cord blood 3351.78 pg/mL versus maternal blood 5769.62 pg/mL (p < 0.001). No differ-ence was found in sFas concentrations between cord arterial and vein blood sera. Statistical difference was found between mean concentration of Fas ligand in maternal blood serum (71.36 pg/mL) and arterial cord blood serum (164.57 pg/mL) p < 0.05 (p = 0.001). Cord arterial blood serum showed much higher concentrations of FasL than maternal blood serum. No difference was found between cord arterial and vein blood sera concentrations of FasL: 164.57 pg/mL vs. 170.00 pg/mL (p = 0.701).

CONCLUSIONS
Obtained results suggest no influence of sFas and FasL production on fetal organism apoptosis. Lowering of sFas concentration in fetal blood could mean the increase of apoptosis in fetal organism compared to maternal. Higher concentration of FasL in cord blood than in mothers suggests higher apoptosis intensification in fetal circulation and no influence of blood flow across placenta on its concentration.

Karowicz-Bilińska|Agata|A| Kowalska-Koprek|Urszula|U| Estemberg|Dorota|D| Sikora-Szubert|Anita|A|


Prevalence of insomnia disorder and sleep apnea in a sample of veterans at risk for cardiovascular disease.

Abstract:
STUDY OBJECTIVES
The objectives of this study were to examine the proportion of study participants screening positive for insomnia disorder and/or sleep apnea in veterans engaged in routine health care and known to be at risk for cardiovascular disease and to compare these proportions with those previously documented in medical records.

METHODS
This was a cross-sectional analysis of baseline data from a randomized clinical intervention trial for patients at risk of cardiovascular disease and a review of study participants' medical records. Participants were veterans ≥ 40 years of age, enrolled in Veterans Affairs primary care, and diagnosed with hypertension and/or hypercholesterolemia. Self-report outcomes were the proportion of patients screening positive for an insomnia disorder and sleep apnea, self-reporting a sleep apnea diagnosis, and endorsing undertreated sleep apnea. Medical record outcomes were the proportion of patients diagnosed with insomnia and sleep apnea.

RESULTS
Participants (n = 420) were veterans (84.8% male) with a mean age of 61.1 years. More than half of the sample (52.1%) screened positive for sleep apnea without prior self-reported diagnosis. More than one-third of the sample (39%) screened positive for an insomnia disorder. Medical records revealed considerably lower rates, with 3.8% diagnosed with insomnia, 20.5% diagnosed with sleep apnea, and about 1% diagnosed with both conditions.

CONCLUSIONS
Undiagnosed and undertreated sleep disorders are common among veterans at risk for cardiovascular disease. Most of the sample (82%) screened positive for, or met, study criteria for sleep apnea or an insomnia disorder. Limitations include the use of self-reported sleep apnea treatment adherence, an insomnia disorder diagnosis based on questionnaire score, and a sample comprised primarily of male veterans. Routine sleep disorders screening in veterans at risk for cardiovascular disease could help to identify those at even greater risk because of the adverse effects of undiagnosed or undertreated sleep disorders.

CLINICAL TRIAL REGISTRATION
Registry; ClinicalTrials.gov; Name: Cardiovascular Intervention Improvement Telemedicine Study; URL: https://clinicaltrials.gov/ct2/show/NCT01142908; Identifier: NCT01142908.

Ulmer|Christi S|CS|
McCant|Felicia|F|
Stechuchak|Karen M|KM|
Olsen|Maren|M|
Bosworth|Hayden B|HB|

D016032:Randomized Controlled Trials as Topic

D007319:Sleep Initiation and Maintenance Disorders

insomnia
sleep apnea
veterans
cardiovascular disease


Incidences of serious infections and tuberculosis among patients receiving anti-tumor necrosis factor-α therapy.

Abstract:
PURPOSE
Anti-tumor necrosis factor-alpha (TNF-α) medications represent a major advancement in the management of chronic inflammatory diseases. However, these agents are associated with increased risks of tuberculosis (TB) and other serious infections. The aim of this study was to evaluate the incidences of such disease among tertiary hospitals in Korea.

MATERIALS AND METHODS
We retrospectively studied patients who received anti-TNF-α therapy; we reviewed serious infections including TB that developed within 6 months after initiation of anti-TNF-α therapy. Data concerning patient demographics, types of anti-TNF-α agents, concomitant immunosuppressive drugs use, and infection details were collected.

RESULTS
A total 175 patients treated with infliximab (n=72) or adalimumab (n=103) with the following conditions were enrolled: Crohn's disease, 34 (19.4%); ulcerative colitis, 20 (11.4%); ankylosing spondylitis, 82 (46.9%); and rheumatoid arthritis, 39 (22.2%). There were 18 cases (6.0%) of serious infections. The most common site of serious infection was the intra-abdomen (n=6), followed by TB (n=3), skin and soft tissue (n=3), bone and joints (n=2), ocular neurons (n=2), lower respiratory tract (n=1), and urinary tract (n=1). Of the 175 patients, only 3 cases showed development of TB. Furthermore, of all those who developed TB, none had taken anti-TB chemoprophylaxis prior to treatment with an anti-TNF agent due to negative screening results.

CONCLUSION
Serious infections with anti-TNF-α therapy were uncommon among tertiary hospitals in Korea; TB was the second most frequent infection. Nevertheless, there were no TB reactivations after anti-TB chemoprophylaxis. Accordingly, physicians should be aware of TB in subjects undergoing anti-TNF-α therapy, especially in countries with a high prevalence of TB.

Yoo|In Kyung|IK|
Choung|Rok Seon|RS|
Hyun|Jong Jin|JJ|
Kim|Seung Young|SY|
Jung|Sung Woo|SW|
Koo|Ja Seol|JS|
Lee|Sang Woo|SW|
Choi|Jai Hyun|JH|
Kim|Ho|H|
Lee|Hong Sik|HS|
Keum|Bora|B|
Kim|Eun Sun|ES|
Jeen|Yoon Tae|YT|

infection
tuberculosis
Tumor necrosis factor-alpha


Successful pregnancy and delivery in a woman with a single ventricle and Eisenmenger syndrome.

Abstract:
BACKGROUND
Patients with a single ventricle represent a rare abnormality found in 1% of patients with congenital heart disease, often discovered during childhood. Without pulmonary stenosis, the disease can progress to fixed pulmonary hypertension. Both pregnancy and delivery are risky events capable of increasing the right-to-left shunt. Pregnancy is contraindicated.

CASE
We report the case of a 27-year-old woman with a single ventricle without pulmonary protection and fixed pulmonary hypertension at 60 mmHg, discovered during a pregnancy. The delivery was obtained by cesarean section with epidural anesthesia and the patient was perioperatively treated with nitric oxide. Though contraindicated, pregnancy and delivery were successfully achieved in this patient.

COMMENT
Patients with single ventricle and Eisenmenger syndrome rarely reach adult life. Pregnancy with this condition is exceptional and fundamentally perturbs hemodynamic stability. In spite of the development of anesthesia and resuscitation and the description of some cases in literature, pregnancy with Eisenmenger syndrome is contraindicated.

Boukhris|M|M| Hakim|K|K| M'saad|H|H| Ouarda|F|F| Boussaada|R|R|

Pregnancy
Single ventricle
Eisenmenger syndrome


Management of nail psoriasis with a single injection of abobotulinum toxin.

Abstract: Nail psoriasis is challenging; as topical agents generally fail and systemic therapies are doubted especially when the involvement of the skin is rather localized. The response of chronic plaque-type psoriasis to botulinum toxin injections is reported in case series that is essentially explained through the modulation of neurogenic inflammation. Herein, we report the successful treatment results of two cases demonstrating different features of nail psoriasis treated by abobotulinum toxin.

psoriasis
abobotulinum toxin
botulinum toxin
dermoscopy
onycholysis
onychoscopy
pitting
psoriatic nail


HPV status in women with high-grade dysplasia on cervical biopsy and preceding negative HPV tests.

Abstract:
INTRODUCTION
A considerable number of patients with high-grade cervical lesions have undergone preceding human papillomavirus (HPV) tests with negative results. In the present study, we attempted to elucidate the factors potentially contributing to the findings by testing biopsied samples from these patients.

MATERIALS AND METHODS
Of the 1654 women with HPV testing and follow-up cervicovaginal biopsies from March 1, 2013 to June 30, 2014, 21 of 252 women (8.3%) with biopsy-confirmed high-grade squamous intraepithelial lesion (HSIL) or worse had had negative results from preceding high-risk (hr)HPV tests. The corresponding paraffin blocks were tested for HPV using the Cobas 4800 system, a DNA microarray against 40 HPV genotypes, and DNA sequencing.

RESULTS
HPV was detected in 20 (95%) of the 21 biopsies with HSIL or worse, including HPV16/18 in 4, non-16/18 hrHPV in 10, and non-hrHPV in 6. HPV59 and HPV45 were 2.2 times more frequently detected than HPV16/18 in these samples. One sample was negative for all 3 tests (5%).

CONCLUSIONS
Our study has demonstrated that 8.3% of women with biopsy-confirmed HSIL or worse had preceding test results that were negative for hrHPV. The vast majority of the biopsied samples had detectable HPV, primarily hrHPV genotypes (67%) with HPV59 and HPV45 predominance. This genotypic prevalence pattern was markedly different from those reported in the general population. Non-hrHPV genotypes contributed to 29% of the cases, and HPV-negative cases were rare. In addition to the limited Cobas testing panel and rare possible HPV-negative HSIL or worse, other possible contributing factors to the discrepancy include cytologic sampling, interference material, technical errors, and reduced L1 gene expression in high-grade lesions.

Ge|Yimin|Y|
Mody|Roxanne R|RR|
Olsen|Randall J|RJ|
Zhou|Haijun|H|
Luna|Eric|E|
Armylagos|Donna|D|
Puntachart|Natu|N|
Hendrickson|Heather|H|
Schwartz|Mary R|MR|
Mody|Dina R|DR|

HPV test
High-grade cervical lesion
Human papillomavirus
Cervical cancer
HPV-cytology co-testing
Papanicolaou test


Plasminogen Activator Inhibitor-1 is Regulated Through Dietary Fat Intake and Heritability: Studies in Twins.

Abstract: In different pathophysiological conditions plasminogen activator inhibitor-1 (PAI-1) plasma concentrations are elevated. As dietary patterns are considered to influence PAI-1 concentration, we aimed to determine active PAI-1 plasma concentrations and mRNA expression in adipose tissue before and after consumption of a high-fat diet (HFD) and the impact of additive genetic effects herein in humans. For 6 weeks, 46 healthy, non-obese pairs of twins (aged 18-70) received a normal nutritionally balanced diet (ND) followed by an isocaloric HFD for 6 weeks. Active PAI-1 plasma levels and PAI-1 mRNA expression in subcutaneous adipose tissue were assessed after the ND and after 1 and 6 weeks of HFD. Active PAI-1 plasma concentrations and PAI-1 mRNA expression in adipose tissue were significantly increased after both 1 and 6 weeks of HFD when compared to concentrations determined after ND (p < .05), with increases of active PAI-1 being independent of gender, age, or changes of BMI and intrahepatic fat content, respectively. However, analysis of covariance suggests that serum insulin concentration significantly affected the increase of active PAI-1 plasma concentrations. Furthermore, the increase of active PAI-1 plasma concentrations after 6 weeks of HFD was highly heritable (47%). In contrast, changes in PAI-1 mRNA expression in fatty tissue in response to HFD showed no heritability and were independent of all tested covariates. In summary, our data suggest that even an isocaloric exchange of macronutrients - for example, a switch to a fat-rich diet - affects PAI-1 concentrations in humans and that this is highly heritable.

Engstler|Anna Janina|AJ|
Frahnow|Turid|T|
Kruse|Michael|M|
Pfeiffer|Andreas Friedrich Hermann|AFH|
Bergheim|Ina|I|

D017395:Plasminogen Activator Inhibitor 1

heritability
twins
PAI-1
adipose tissue
nutrition
insulin resistance


Cost-effectiveness of first-trimester screening with early preventative use of aspirin in women at high risk of early-onset pre-eclampsia.

Abstract:
OBJECTIVE
Pre-eclampsia (PE) remains a leading cause of maternal and fetal morbidity and mortality. A first-trimester screening algorithm predicting the risk of early-onset PE has been developed and validated. Early prediction coupled with initiation of aspirin at 11-13 weeks in women identified as high risk is effective at reducing the prevalence of early-onset PE. The aim of this study was to evaluate the cost-effectiveness of this first-trimester screening program coupled with early use of low-dose aspirin in women at high risk of developing early-onset PE, in comparison to current practice in Canada.

METHODS
A decision analysis was performed based on a theoretical population of 387 516 live births in Canada in 1 year. The clinical and financial impact of early preventative screening using the Fetal Medicine Foundation algorithm for prediction of early-onset PE coupled with early (< 16 weeks) use of low-dose aspirin in those at high risk was simulated and compared with current practice using decision-tree analysis. The probabilities at each decision point and associated costs of utilized resources were calculated based on published literature and public databases.

RESULTS
Of the theoretical 387 516 births per year, the estimated prevalence of early PE based on first-trimester screening and aspirin use was 705 vs 1801 cases based on the current practice. This was associated with an estimated total cost of C$9.52 million with the first-trimester screening program compared with C$23.91 million with current practice for the diagnosis and management of women with early-onset PE. This equals an annual cost saving to the Canadian healthcare system of approximately C$14.39 million.

CONCLUSIONS
The implementation of a first-trimester screening program for PE and early intervention with aspirin in women identified as high risk for early PE has the potential to prevent a significant number of early-onset PE cases with a substantial associated cost saving to the healthcare system in Canada. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

cost-effectiveness
first-trimester screening
aspirin
early-onset pre-eclampsia


Modelling impacts of climate change and socio-economic change on the Ganga, Brahmaputra, Meghna, Hooghly and Mahanadi river systems in India and Bangladesh.

Abstract: The Ganga-Brahmaputra-Meghna (GBM) River System, the associated Hooghly River and the Mahanadi River System represent the largest river basins in the world serving a population of over 780 million. The rivers are of vital concern to India and Bangladesh as they provide fresh water for people, agriculture, industry, conservation and support the Delta System in the Bay of Bengal. Future changes in both climate and socio-economics have been investigated to assess whether these will alter river flows and water quality. Climate datasets downscaled from three different Global Climate Models have been used to drive a daily process based flow and water quality model. The results suggest that due to climate change the flows will increase in the monsoon period and also be enhanced in the dry season. However, once socio-economic changes are also considered, increased population, irrigation, water use and industrial development reduce water availability in drought conditions, threatening water supplies and posing a threat to river and coastal ecosystems. This study, as part of the DECCMA (Deltas, vulnerability and Climate Change: Migration and Adaptation) project, also addresses water quality issues, particularly nutrients (N and P) and their transport along the rivers and discharge into the Delta System. Climate will alter flows, increasing flood flows and changing pollution dilution factors in the rivers, as well as other key processes controlling water quality. Socio-economic change will affect water quality, as water diversion strategies, increased population and industrial development alter the water balance and enhance fluxes of nutrients from agriculture, urban centers and atmospheric deposition.

Whitehead|Paul G|PG|
Jin|Li|L|
Macadam|Ian|I|
Janes|Tamara|T|
Sarkar|Sananda|S|
Rodda|Harvey J E|HJE|
Sinha|Rajiv|R|
Nicholls|Robert J|RJ|

Climate change
Socio-economics
Ganga
Mahanadi
Water quality modelling
RCP 8.5


Clinical Study of Intravenous, Low-Dose Recombinant Tissue Plasminogen Activator for Acute Cerebral Infarction: Comparison of Treatment within 3 Hours versus 3-4.5 Hours.

Abstract:
BACKGROUND
An intravenous recombinant tissue plasminogen activator (rt-PA, alteplase .6 mg/kg) for acute cerebral infarction within 3 hours of onset was approved in Japan in 2005. The treatment window was subsequently extended to within 4.5 hours of onset. However, few Japanese studies have compared the efficacy and safety of rt-PA therapy between patients treated within 3 hours and patients treated within 3-4.5 hours.

METHODS
This study included 323 patients who received rt-PA for acute cerebral infarction within 3 hours or 3-4.5 hours between April 2007 and March 2017. Patients' characteristics, outcomes (modified Rankin Scale [mRS] score at 3 months), and symptomatic intracranial hemorrhage (sICH) were retrospectively investigated.

RESULTS
Of the 323 patients, 219 were treated within 3 hours and 104 were treated at 3-4.5 hours. Among patients receiving rt-PA alone, 154 were treated within 3 hours (3-hour group), and 69 were treated at 3-4.5 hours (3-4.5-hour group). There was no difference in the sICH rate (3.9% versus 4.3%, respectively; P = 1.00) or mRS score of 0-1 (38.3% versus 40.6%, respectively; P = .76) between these groups. In patients receiving additional neuroendovascular therapy, 65 were in the 3-hour group and 35 were in the 3-4.5-hour group. There was no significant difference in the sICH rate (1.5% versus 0%, respectively; P = 1.00) or mRS score of 0-1 (30.8% versus 31.4%, respectively; P = 1.00) between these groups.

CONCLUSIONS
Low-dose rt-PA treatment from either 3 or 3-4.5 hours after acute cerebral infarction has the same efficacy and safety.

D000208:Acute Disease
D000368:Aged
D000369:Aged, 80 and over
D002544:Cerebral Infarction
D003131:Combined Modality Therapy
D004185:Disability Evaluation
D057510:Endovascular Procedures
D005260:Female
D005343:Fibrinolytic Agents
D006801:Humans
D007262:Infusions, Intravenous
D020300:Intracranial Hemorrhages
D007564:Japan
D008297:Male
D008875:Middle Aged
D011994:Recombinant Proteins
D020127:Recovery of Function
D012189:Retrospective Studies
D015912:Thrombolytic Therapy
D013997:Time Factors
D010959:Tissue Plasminogen Activator
D016896:Treatment Outcome


Enhanced recovery protocols in total joint arthroplasty: a review of the literature and their implementation.

Abstract:
BACKGROUND
During recent years, there has been an exponential demand for joint arthroplasty, which has coincided with the global economic recession. In response, the management of patients following arthroplasty is continuously evolving, with the average inpatient length of stay decreasing from weeks to days, and more recently, we have witnessed the development of "outpatient arthroplasty" as a novel concept which aims to address the high volume of patients. The reduction in length of stay has been made possible via implementation of "enhanced recovery programmes" encompassing each stage of the patient journey. Such programmes have aimed to maximise efficiency, whilst maintaining patient satisfaction and achieving exceptional functional outcomes.

OBJECTIVE
We have undertaken a thorough review the literature in relation to enhanced recovery programmes (ERPs) and the research that has underpinned individual elements of enhanced recovery. A literature search of enhanced recovery protocols was carried out using PubMed, Cochrane, Embase and OVID. No language restrictions were imposed on the search.

REVIEW
ERPs represent a multifactorial framework which may be subdivided into several phases. Pre-operative education programmes, outpatient consultation, pre-anaesthetic assessment, pre-procedural physiotherapy, day-of-surgery admission, pre-operative medications, type of anaesthesia, blood loss reduction protocols, multimodal analgesia delivery, day-of-surgery mobilisation, thromboembolic prophylaxis and ongoing rehabilitation are essential in enhanced recovery.

CONCLUSION
These successful strategies have streamlined the patient pathway of arthroplasty surgery in a cost-effective manner, whilst reducing length of hospital stay and maintaining patient outcomes. Further studies are required to appropriately quantify the impact of individual variables and development of an internationally agreed ERP.

Galbraith|A S|AS|
McGloughlin|E|E|
Cashman|J|J|

Total joint arthroplasty
Enhanced recovery programme
Enhanced recovery after surgery
Rapid recovery
Total hip arthroplasty
Total joint replacement
Total knee arthroplasty


Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study.

Abstract:
OBJECTIVE
To investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD).

METHODS
The register-based MEDALZ cohort, including all community-dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register. To study new users, persons who had any BZDR use during the year preceding the AD diagnosis were excluded. For each person initiating BZDR use (n = 10 380), 2 nonusers (n = 20 760) were matched on age, gender, and time since AD diagnosis. The outcome was 180-day mortality, and BZDR use was compared with nonuse with Cox regression. Multivariable analyses were adjusted for Charlson comorbidity index, socioeconomic position, hip fractures, psychiatric disorders, substance abuse, stroke, and other psychotropic drug use.

RESULTS
During the follow-up, 5 excess deaths per 100 person-years occurred during BZDR use in comparison to nonuse, and mortality rates were 13.4 (95% confidence interval [CI], 12.2-14.5) and 8.5 (95% CI, 7.9-9.1), respectively. Benzodiazepine and related drug use was associated with an increased risk of death (adjusted hazard ratio = 1.4 [95% CI, 1.2-1.6]), and the association was significant from the initiation of use. Benzodiazepine use was associated with an increased risk of death, whereas benzodiazepine-related drug use was not.

CONCLUSIONS
Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first-line option for symptomatic treatment of AD.

Saarelainen|Laura|L|0000-0003-2542-8137 Tolppanen|Anna-Maija|AM| Koponen|Marjaana|M| Tanskanen|Antti|A| Tiihonen|Jari|J| Hartikainen|Sirpa|S| Taipale|Heidi|H|

benzodiazepines
Alzheimer disease
cohort study
Prescription Register
mortality
drug safety


Context dependent regulatory patterns of the androgen receptor and androgen receptor target genes.

Abstract:
BACKGROUND
Expression of the androgen receptor (AR) is associated with androgen-dependent proliferation arrest and terminal differentiation of normal prostate epithelial cells. Additionally, activation of the AR is required for survival of benign luminal epithelial cells and primary cancer cells, thus androgen deprivation therapy (ADT) leads to apoptosis in both benign and cancerous tissue. Escape from ADT is known as castration-resistant prostate cancer (CRPC). In the course of CRPC development the AR typically switches from being a cell-intrinsic inhibitor of normal prostate epithelial cell proliferation to becoming an oncogene that is critical for prostate cancer cell proliferation. A clearer understanding of the context dependent activation of the AR and its target genes is therefore desirable.

METHODS
Immortalized human prostate basal epithelial EP156T cells and progeny cells that underwent epithelial to mesenchymal transition (EMT), primary prostate epithelial cells (PrECs) and prostate cancer cell lines LNCaP, VCaP and 22Rv1 were used to examine context dependent restriction and activation of the AR and classical target genes, such as KLK3. Genome-wide gene expression analyses and single cell protein analyses were applied to study the effect of different contexts.

RESULTS
A variety of growth conditions were tested and found unable to activate AR expression and transcription of classical androgen-dependent AR target genes, such as KLK3, in prostate epithelial cells with basal cell features or in mesenchymal type prostate cells. The restriction of androgen- and AR-dependent transcription of classical target genes in prostate basal epithelial cells was at the level of AR expression. Exogenous AR expression was sufficient for androgen-dependent transcription of AR target genes in prostate basal epithelial cells, but did not exert a positive feedback on endogenous AR expression. Treatment of basal prostate epithelial cells with inhibitors of epigenetic gene silencing was not efficient in inducing androgen-dependent transcription of AR target genes, suggesting the importance of missing cofactor(s).

CONCLUSIONS
Regulatory mechanisms of AR and androgen-dependent AR target gene transcription are insufficiently understood and may be critical for prostate cancer initiation, progression and escape from standard therapy. The present model is useful for the study of context dependent activation of the AR and its transcriptome.

Olsen|Jan Roger|JR|0000-0001-6547-431X
Azeem|Waqas|W|
Hellem|Margrete Reime|MR|
Marvyin|Kristo|K|
Hua|Yaping|Y|
Qu|Yi|Y|
Li|Lisha|L|
Lin|Biaoyang|B|
Ke|Xi- Song|X|
Øyan|Anne Margrete|AM|
Kalland|Karl- Henning|K|

D015972:Gene Expression Regulation, Neoplastic

Androgen receptor
Differentiation
Epithelial to mesenchymal transition
Human prostate cancer
Stem cell


Subcellular distribution and activity of mechanistic target of rapamycin in aged retinal pigment epithelium.

Abstract:
PURPOSE
Inhibiting mechanistic target of rapamycin (mTOR) by pharmacological or genetic approaches can extend lifespan in mammals. The kinase activity of mTOR is controlled by upstream regulatory proteins and its subcellular localization. The purpose of this study was to characterize age-related alterations and functional consequences of mTOR signaling in the postmitotic RPE cells.

METHODS
Activity of mTOR complex 1 (mTORC1) was monitored by measuring phosphorylation status of its downstream effector protein S6, in either cultured human RPE cells or RPE explants prepared from mice at different ages. Subcellular distribution of mTOR was investigated by immunofluorescent staining of RPE culture or flatmount. The signaling of mTORC1 was modulated by either overexpression of a small guanosine triphosphatase, Ras homolog enriched in brain (Rheb), or disruption of the Ragulator complex with small interference RNA targeting p18. The effects of mTOR pathway on degradation of phagocytosed photoreceptor outer segments (POS) were determined by measuring the turnover rate of rhodopsin.

RESULTS
Aged RPE cells had more lysosome-associated mTOR and had increased response to amino acid stimulation. The lysosome distribution was essential for mTORC1 function, as disruption of the Ragulator complex abolished mTORC1 activation by amino acids. Increased mTORC1 activity caused decreased rate of degradation of internalized POS in the RPE.

CONCLUSIONS
Aging changes the subcellular localization and function of mTOR in the RPE. Increased mTORC1 inhibits POS degradation and may further exacerbate lysosome dysfunction of aged RPE.

Yu|Bo|B| Xu|Pei|P| Zhao|Zhenyang|Z| Cai|Jiyang|J| Sternberg|Paul|P| Chen|Yan|Y|

D000076222:Mechanistic Target of Rapamycin Complex 1

D055214:Retinal Photoreceptor Cell Outer Segment

aging
retinal pigment epithelium
mTOR
signaling
lysosome
eye


What has health technology assessment ever done for us?

Abstract: Health technology assessment (HTA) has over the past three decades become a well-established part of decisions about allocation of resources in many countries. Despite this, little is known about HTA's impact on health systems. Few studies have evaluated the benefits of HTA for health outcomes, for access to care or for public budgets. In contrast, HTA has relatively clear upfront costs, which could potentially discourage policy-makers from establishing HTA agencies, especially in low income countries with restricted resources. It may be premature, though, to dismiss this approach altogether, as less tangible modernizing goals are still significant.

health technology assessment
equity
governance
policy evaluation
policy research


An introductory guide to conducting the Trier Social Stress Test.

Abstract: The Trier Social Stress Test (TSST) is a reliable biopsychological tool to examine the effects of acute stress on psychological and physiological functioning in humans. While the TSST reliably increases hypothalamic-pituitary-adrenal axis activation, amongst other biomarkers, through a combination of social evaluative threat and uncontrollability, the original protocol is limited in methodological detail that has impacted its reproducibility. Although many studies include a mock job interview and surprise arithmetic task, there are large variations in the timing of events, the number and method of biological (e.g., cortisol) sampling, the administration of a glucose drink, set-up of equipment and rooms, panel composition, and panel interaction with participants. We provide an overview of the potential impact of methodological variations on the stress (cortisol) response. Importantly, we also provide a step-by-step guide as a laboratory manual on how to conduct the TSST. This introductory guide may be a useful and time-saving resource that may also improve the scientific standard and reliability of the reported psychobiological stress effects in future studies.

Labuschagne|Izelle|I| Grace|Caitlin|C| Rendell|Peter|P| Terrett|Gill|G| Heinrichs|Markus|M|

TSST
Humans
Cortisol
HPA axis
Mental arithmetic
Public speaking


Characterization, validation and application of a DNA microarray for the detection of mandatory and other waterborne pathogens.

Abstract: Culture methods for the detection of indicator bacteria are currently used for detection of waterborne bacteria. The need for an increased range of analyzed bacteria coupled with the obtainment of rapid and early results justify the development of a DNA microarray for the identification of waterborne pathogens. This DNA microarray has 16 implanted probes with a median size of 147 bases, targeting 12 different parameters, including all mandatory indicator microorganisms, such as Escherichia coli, Clostridium perfringens, Pseudomonas aeruginosa, Staphylococcus aureus, total and fecal coliforms and enterococci. The validation performed with DNA extracted from pure microbial cultures showed the suitability of the probes for detection of the target microorganism. To overcome the high dilution of water samples it was included either a prior culture step of bacterial contaminants retained after filtering 100 ml of water, or a 10-fold increase in the volume of filtered water, that resulted in the increase of the detected bacteria. The analysis of complex environmental water samples using culture methods and the DNA microarray revealed that the latter detected the same parameters plus other bacteria tested only in the DNA microarray. The results show that this DNA microarray may be a useful tool for water microbiological surveillance.

Gomes|Maria|M|
Vieira|Helena|H|
Vale|Filipa F|FF|

D020411:Oligonucleotide Array Sequence Analysis

DNA microarray
waterborne pathogen
indicator bacteria
bacterial detection
drinking water quality


Does the Distribution of Empanelled Hospitals have an Impact on the Utilization of Services under State Insurance Scheme?

Abstract:
Context
Tamil Nadu's Chief Minister's Comprehensive Health Insurance Scheme (CMCHIS) aims at reducing inequity by making the health service affordable and available by roping in both the public and private providers.

Aims
This study aims to find if there exist any inter-district disparity in the distribution of hospitals empaneled and utilization of services under the CMCHIS scheme.

Settings and Design
A secondary data analysis was done using the CMCHIS data on hospitals empanelled and number of claims made in the scheme for the year 2018.

Subjects and Methods
The districts were classified into high-developed district (HDD), middle-developed district (MDD), and low-developed district (LDD) based on the Human Development Index. Availability of hospital services was calculated as the number of empanelled hospitals/100,000 families enrolled. Utilization was calculated as the number of claims made by people living in the district per one lakh families enrolled and number of claims made by hospitals under CMCHIS/100,000 enrolled.

Statistical Analysis Used
The relationship between enrolment ratio, hospital availability, number of claims made, and Human Development Index across districts was examined using the Pearson's Correlation analysis.

Results
Enrolment was highest in the LDDs (22.8%), followed by MDDs (21.9%) and HDDs (18.7%). The number of hospitals per 100,000 families enrolled was the highest in HDDs (8.0) and lowest in LDDs (4.6). The utilization was the highest in HDD followed by MDD and lowest in LDD.

Conclusions
The disparity in the hospitals availability and utilization between districts should be addressed by adopting a targeting approach giving priorities to empanelling hospitals in the less-developed districts.

Chief Minister's Comprehensive health insurance scheme


Cellular and molecular characterization of multiplex autism in human induced pluripotent stem cell-derived neurons.

Abstract:
Background
Autism spectrum disorder (ASD) is a neurodevelopmental disorder with pronounced heritability in the general population. This is largely attributable to the effects of polygenic susceptibility, with inherited liability exhibiting distinct sex differences in phenotypic expression. Attempts to model ASD in human cellular systems have principally involved rare de novo mutations associated with ASD phenocopies. However, by definition, these models are not representative of polygenic liability, which accounts for the vast share of population-attributable risk.

Methods
Here, we performed what is, to our knowledge, the first attempt to model multiplex autism using patient-derived induced pluripotent stem cells (iPSCs) in a family manifesting incremental degrees of phenotypic expression of inherited liability (absent, intermediate, severe). The family members share an inherited variant of uncertain significance (VUS) in GPD2, a gene that was previously associated with developmental disability but here is insufficient by itself to cause ASD. iPSCs from three first-degree relatives and an unrelated control were differentiated into both cortical excitatory (cExN) and cortical inhibitory (cIN) neurons, and cellular phenotyping and transcriptomic analysis were conducted.

Results
cExN neurospheres from the two affected individuals were reduced in size, compared to those derived from unaffected related and unrelated individuals. This reduction was, at least in part, due to increased apoptosis of cells from affected individuals upon initiation of cExN neural induction. Likewise, cIN neural progenitor cells from affected individuals exhibited increased apoptosis, compared to both unaffected individuals. Transcriptomic analysis of both cExN and cIN neural progenitor cells revealed distinct molecular signatures associated with affectation, including the misregulation of suites of genes associated with neural development, neuronal function, and behavior, as well as altered expression of ASD risk-associated genes.

Conclusions
We have provided evidence of morphological, physiological, and transcriptomic signatures of polygenic liability to ASD from an analysis of cellular models derived from a multiplex autism family. ASD is commonly inherited on the basis of additive genetic liability. Therefore, identifying convergent cellular and molecular phenotypes resulting from polygenic and monogenic susceptibility may provide a critical bridge for determining which of the disparate effects of rare highly deleterious mutations might also apply to common autistic syndromes.

Lewis|Emily M A|EMA|
Meganathan|Kesavan|K|
Baldridge|Dustin|D|
Gontarz|Paul|P|
Zhang|Bo|B|
Bonni|Azad|A|
Constantino|John N|JN|
Kroll|Kristen L|KL|0000-0002-5450-6694

Multiplex autism
Transcriptomics
Cortical excitatory neurons
Cortical inhibitory neurons
Gene networks
Neurodevelopment
iPSC modeling


Classic cases revisited - Death of a nurse and the anatomy of error.

Abstract: The tragic case of Mayra Cabrera who died as a result of wrong route drug administration is notable as it was the first time a verdict of unlawful killing was recorded against an NHS Trust. Error within medicine is a significant cause of patient morbidity and mortality. We explore the costs of error, the dynamics of error causation, the role of both the individual and institution in accountability for error, as well as transferrable lessons from other industries to reduce error.


Associations between daily mortality in London and combined oxidant capacity, ozone and nitrogen dioxide.

Abstract: Both nitrogen dioxide (NO2) and ozone (O3) are powerful oxidants in ambient air that are intimately linked through atmospheric chemistry and which continuously interchange over very short timescales. Based upon atmospheric chemistry alone, there is a strong, a priori, reason for considering O3 and NO2 together in epidemiological studies, rather than either of the two pollutants separately in single-pollutant models. This paper compares two approaches to this, using Ox, defined as O3 + NO2, as a single metric and also using O3 and NO2 together in two-pollutant models. We hypothesised that the magnitude of the association between Ox and daily mortality would be greater than for NO2 and O3 individually. Using collocated hourly measurements for O3 and NO2 in London, from 2000 to 2005, we carried out a time series analysis of daily mortality. We investigated O3, NO2 and Ox individually in single-pollutant Poisson regression models and NO2 and O3 jointly in two-pollutant models in both all-year and season-specific analyses. We observed larger associations for mean 24-h concentrations of Ox (1.30 % increase in mortality per 10 ppb) than for O3 (0.87 %) and NO2 (0 %) individually. However, when analysed jointly in two-pollutant models, associations for O3 (1.54 %) and NO2 (1.07 %) were comparable to the Ox association. Season-specific analyses broadly followed this pattern irrespective of whether the Ox concentrations were driven by O3 production (summer) or depletion (winter). This novel approach in air pollution epidemiology captures the simultaneous impact of both oxidants whilst avoiding many of the statistical issues associated with two-pollutant models and potentially simplifies health impact calculations.

Williams|M L|ML|
Atkinson|R W|RW|
Anderson|H R|HR|
Kelly|F J|FJ|

Mortality
Oxidants
Ozone
Nitrogen dioxide
Time series


How to Assess the Biomechanical Risk Levels in Beekeeping.

Abstract: Beekeepers are at particular risk of developing work-related musculoskeletal disorders, but many of the studies lack detailed exposure assessment. To evaluate the biomechanical overload exposure in a specific farming activity, a multitasking model has been developed through the characterization of 37 basic operational tasks typical of the beekeeping activity. The Occupational Repetitive Actions (OCRA) Checklist and the National Institute for Occupational Safety and Health (NIOSH) Lifting Index methodologies have been applied to these elementary tasks to evaluate the exposure, and the resulting risk indices have been time-weighted averaged. Finally, an easy access, computer-assisted toolkit has been developed to help the beekeepers in the biomechanical risk assessment process. The risk of biomechanical overload for the upper limbs ranges from acceptable (maintenance and recovery of woody material and honey packaging with dosing machine tasks) to high (distribution of the top supers) risk level. The risk for back injury is always borderline in women and increases with exposure time, whereas it ranges from acceptable to borderline in men. The definition of the biomechanical risk levels allows for planning of corrective actions aimed at preventing and reducing the risk of musculoskeletal disorders through engineering, administrative, and behavioral interventions. The methodology can be used for risk assessment in other mainly manual agricultural activities.

musculoskeletal disorders
computer-assisted toolkit
Biomechanical risk assessment
exposure level
farmers


Development and Evaluation of a Novel Oral Mucoadhesive Ointment Containing Pomegranate Peel Extract as an Adjuvant for Oral Hygiene of Dogs.

Abstract: Herbal therapies are used worldwide to treat a variety of health conditions, including dental conditions in veterinary medicine. In this context, the use of medicinal plant-based formulations as potential therapeutics and preventatives in veterinary dentistry is worth highlighting. The objective of the present study was to develop a mucoadhesive ointment formulation, named orabase, that contained pomegranate extract for use in the oral cavity of dogs, with the aim of improving their oral hygiene. The hydroalcoholic extracts of pomegranate peels was incorporated into the orabase in 3 different concentrations. The formulations were subjected to in vitro microbiological testing by a modified disc-diffusion method to study the susceptibility of microorganisms collected from the oral cavities of the dogs. The samples were taken from the buccal mucosa of dogs having the same management and diet. The most effective formulation was submitted to physicochemical tests to evaluate the functionality of the product, namely pH, swelling index, spreadability, and mechanical properties (hardness, cohesiveness, and adhesiveness). The formulation containing 25.0% w/w of the extract was considered most suitable for the intended use as it showed antiseptic activity and demonstrated a swelling index of approximately 35% in the first 20 minutes of the test, high spreadability, and suitable mechanical properties. The results suggest that the product obtained from pomegranate peel extract is a viable option for use to improve oral hygiene, helping to reduce the bacterial component of dental plaque in dogs.

pomegranate peel extract
oral hygiene
dogs
veterinary dentistry
orabase
complementary and alternative medicine


On Path to Informing Hierarchy of Eplet Mismatches as Determinants of Kidney Transplant Loss.

Abstract:
Introduction
To mitigate risks related to human leukocyte antigen (HLA) incompatibility, we assessed whether certain structurally defined HLA targets present in donors but absent from recipients, known as eplet mismatches (EMM), are associated with death-censored graft failure (DCGF).

Methods
We studied a cohort of 118,313 American 0% panel reactive antibodies (PRA) first kidney transplant recipients (2000 to 2015) from the Scientific Registry of Transplant Recipients. Imputed allele-level donor and recipient HLA-A, -B, -C, -DRB1, and -DQB1 genotypes were converted to the repertoire of EMM. We fit survival models for each EMM with significance thresholds corrected for false discovery rate and validated those in an independent PRA > 0% cohort. We conducted network-based analyses to model relationships among EMM and developed models to select the subset of EMM most predictive of DCGF.

Results
Of 412 EMM observed, 119 class I and 118 class II EMM were associated with DCGF. Network analysis showed that although 210 eplets formed profiles of 2 to 12 simultaneously occurring EMMs, 202 were singleton EMMs that were not involved in any profile. A variable selection procedure identified 55 single HLA class I and II EMMs in 70% of the dataset; of those, 15 EMMs (9 singleton and 6 involved in profiles) were predictive of DCGF in the remaining dataset.

Conclusion
Our analysis distinguished increasingly smaller subsets of EMMs associated with increased risk of DCGF. Validation of these EMMs as important predictors of transplant outcomes (in contrast to acceptable EMMs) in datasets with measured allele-level genotypes will support their role as immunodominant EMMs worthy of consideration in organ allocation schemes.

Mohammadhassanzadeh|Hossein|H|
Oualkacha|Karim|K|
Zhang|Wenmin|W|
Klement|William|W|
Bourdiec|Amelie|A|
Lamsatfi|Jennat|J|
Yi|Yang|Y|
Foster|Bethany|B|
Keown|Paul|P|
Gebel|Howard M|HM|
Claas|Frans|F|
Sapir-Pichhadze|Ruth|R|
|||

eplet
kidney transplantation
human leukocyte antigens
graft failure
epitope
immunogenicity


2021 consensus statement for preventing and managing low back pain in elite and subelite adult rowers.

Abstract:
PURPOSE
To synthesise evidence on low back pain (LBP) in adult rowers and to create a consensus statement to inform clinical practice.

METHODS
There were four synthesis steps that informed the consensus statement. In step one, seven expert clinicians and researchers established the scope of the consensus statement and conducted a survey of experienced and expert clinicians to explore current practice. In step two, working groups examined current evidence relating to key scope questions and summarised key issues. In step three, we synthesised evidence for each group and used a modified Delphi process to aid in the creation of the overall consensus statements. Finally, in step four, we combined information from step three with the findings of the clinician survey (and with athlete and coach input) to produce recommendations for clinical practice.

RESULTS
The scope of the consensus statement included epidemiology; biomechanics; management; the athlete's voice and clinical expertise. Prevention and management of LBP in rowers should include education on risk factors, rowing biomechanics and training load. If treatment is needed, non-invasive management, including early unloading from aggravating activities, effective pain control and exercise therapy should be considered. Fitness should be maintained with load management and progression to full training and competition. The role of surgery is unclear. Management should be athlete focused and a culture of openness within the team encouraged.

CONCLUSION
Recommendations are based on current evidence and consensus and aligned with international LBP guidelines in non-athletic populations, but with advice aimed specifically at rowers. We recommend that research in relation to all aspects of prevention and management of LBP in rowers be intensified.


Skylarks trade size and energy content in weed seeds to maximize total ingested lipid biomass.

Abstract: The trade-off between forage quality and quantity has been particularly studied in herbivore organisms, but much less for seed eating animals, in particular seed-eating birds which constitute the bulk of wintering passerines in European farmlands. The skylark is one of the commonest farmland birds in winter, mainly feeding on seeds. We focus on weed seeds for conservation and management purposes. Weed seeds form the bulk of the diet of skylarks during winter period, and although this is still a matter for discussion, weed seed predation by granivorous has been suggested as an alternative to herbicides used to regulate weed populations in arable crops. Our objectives were to identify whether weed seed traits govern foraging decisions of skylarks, and to characterize key seed traits with respect to size, which is related to searching and handling time, and lipid content, which is essential for migratory birds. We combined a single-offer experiment and a multiple-offer one to test for feeding preferences of the birds by estimating seed intake on weed seed species differing in their seed size and seed lipid content. Our results showed (1) a selective preference for smaller seeds above a threshold of seed size or seed size difference in the pair and, (2) a significant effect of seed lipid biomass suggesting a trade-off between foraging for smaller seeds and selecting seeds rich in lipids. Skylarks foraging decision thus seems to be mainly based on seed size, that is presumably a 'proxy' for weed seed energy content. However, there are clearly many possible combinations of morphological and physiological traits that must play crucial role in the plant-bird interaction such as toxic compound or seed coat.

Gaba|Sabrina|S| Collas|Claire|C| Powolny|Thibaut|T| Bretagnolle|François|F| Bretagnolle|Vincent|V|

Skylark
Weed
Trade-offs
Lipid content
Seed size
Optimal foraging


Differential Subcellular Distribution and Translocation of Seven 14-3-3 Isoforms in Response to EGF and During the Cell Cycle.

Abstract: Multiple isoforms of 14-3-3 proteins exist in different organisms. In mammalian cells, 14-3-3 protein has seven isoforms (α/β, ε, η, γ, σ, θ/τ, and δ/ζ), with α and δ representing the phosphorylated versions of β and ζ, respectively. While the existence of multiple isoforms may represent one more level of regulation in 14-3-3 signaling, our knowledge regarding the isoform-specific functions of 14-3-3 proteins is very limited. Determination of the subcellular localization of the different 14-3-3 isoforms could give us important clues of their specific functions. In this study, by using indirect immunofluorescence, subcellular fractionation, and immunoblotting, we studied the subcellular localization of the total 14-3-3 protein and each of the seven 14-3-3 isoforms; their redistribution throughout the cell cycle; and their translocation in response to EGF in Cos-7 cells. We showed that 14-3-3 proteins are broadly distributed throughout the cell and associated with many subcellular structures/organelles, including the plasma membrane (PM), mitochondria, ER, nucleus, microtubules, and actin fibers. This broad distribution underlines the multiple functions identified for 14-3-3 proteins. The different isoforms of 14-3-3 proteins have distinctive subcellular localizations, which suggest their distinctive cellular functions. Most notably, 14-3-3ƞ is almost exclusively localized to the mitochondria, 14-3-3γ is only localized to the nucleus, and 14-3-3σ strongly and specifically associated with the centrosome during mitosis. We also examined the subcellular localization of the seven 14-3-3 isoforms in other cells, including HEK-293, MDA-MB-231, and MCF-7 cells, which largely confirmed our findings with Cos-7 cells.

D048948:14-3-3 Proteins
D000818:Animals
D019556:COS Cells
D002453:Cell Cycle
D002462:Cell Membrane
D002467:Cell Nucleus
D002522:Chlorocebus aethiops
D003593:Cytoplasm
D004815:Epidermal Growth Factor
D057809:HEK293 Cells
D006801:Humans
D061986:MCF-7 Cells
D008928:Mitochondria
D008938:Mitosis
D020033:Protein Isoforms
D021381:Protein Transport
D013347:Subcellular Fractions

isoforms
14-3-3 proteins
subcellular localization
mitochondria
nucleus
actin fibers
centrosome
and microtubules


Aromatic compound-degrading taxa in an anoxic coal seam microbiome from the Surat Basin, Australia.

Abstract: Methane is an important energy resource internationally, and a large proportion of this methane is produced by microbial communities living in coal seams. Despite the value of this resource for human energy security, our understanding of the metabolic roles played by specific taxa during the biodegradation of coal to methane in situ is quite limited. In order to develop a greater understanding of microbial catabolism on coal, a community from a coal seam in the Surat Basin, Australia, was incubated on 10 different aromatic organic compounds: coronene, benzo[a]pyrene, pyrene, phenanthrene, naphthalene, ethylbenzene, phenol, benzoate, vanillate and syringate. Each of these aromatic compounds either occurs in coal or is a possible product of the coal biodegradation process. 16S rRNA sequencing revealed substantial changes to each community in response to each aromatic carbon substrate provided. Abundant taxa from these substrate-specific communities were identified and their probable catabolic roles proposed based on literature searches of related taxa. This study is the first to link specific coal seam taxa to aromatic substrates available in coal seam environments. Two conceptual models of the putative degradation pathways and key taxa responsible are proposed.

C Campbell|Bronwyn|B|
Gong|Se|S|
Greenfield|Paul|P|
J Midgley|David|D|
T Paulsen|Ian|I|
C George|Simon|S|

aromatic compound
degradation pathway
aromatic hydrocarbon
coal seam gas
coal seam microbiology
coalbed methane


Impulse oscillometry in adults with bronchiectasis.

Abstract:
RATIONALE
The usefulness of impulse oscillometry (IOS) in bronchiectasis has not been systematically investigated.

OBJECTIVES
To determine the usefulness of IOS parameters and their correlation with radiology, disease severity, sputum bacteriology, and spirometry, and to compare the changes in IOS parameters during exacerbations and convalescence of bronchiectasis.

METHODS
We recruited 100 patients with bronchiectasis and 28 healthy subjects. Receiver operating characteristic curve was plotted to analyze the diagnostic performance of IOS parameters. Chest high-resolution computed tomography (HRCT), Bronchiectasis Severity Index (BSI) assessment, sputum culture, and spirometry were performed. Correlation between IOS parameters and clinical indices was determined using the Spearman model. Changes in IOS parameters, compared with spirometry, during exacerbation were assessed in 16 patients with bronchiectasis.

MEASUREMENTS AND MAIN RESULTS
IOS parameters (in particular, resonant frequency) could discriminate patients with bronchiectasis from healthy subjects. Higher levels of IOS parameters were associated with Pseudomonas aeruginosa infection, dyshomogeneity, higher BSI and HRCT score, more bronchiectatic lobes, and cystic bronchiectasis (all P < 0.05). All IOS parameters but lung resistance at 5 Hz were positively correlated with the duration of bronchiectasis symptoms, number of bronchiectatic lobes, HRCT total scores, and BSI (all P < 0.05), but not sputum bacterial density (P > 0.05). IOS parameters, but not spirometric parameters, were not statistically different between peripheral and peripheral plus central segment bronchiectasis (all P > 0.05). Increased frequency dependence (higher resonance frequency or reactance area) was more likely to be associated with lower HRCT scores (≤5) than FEV1. Compared with FEV1, any single IOS parameter being abnormal was more common in mild bronchiectasis, particularly in patients with HRCT score of 5 or lower. IOS parameters were not statistically different from baseline to exacerbations and convalescence (all P > 0.05).

CONCLUSIONS
IOS parameters correlate with clinical indices and could reflect peripheral airway abnormality. An increased number of aberrant IOS parameters signals poorer clinical conditions. Increased frequency dependence might be a sensitive marker of mild bronchiectasis. Any single IOS parameter being abnormal sensitively reflects mild bronchiectasis. IOS parameters do not change significantly during bronchiectasis exacerbations. Clinical Trial registered with www.clinicaltrials.gov (NCT01761214).

Guan|Wei-jie|WJ| Gao|Yong-hua|YH| Xu|Gang|G| Lin|Zhi-ya|ZY| Tang|Yan|Y| Li|Hui-min|HM| Lin|Zhi-min|ZM| Zheng|Jin-ping|JP| Chen|Rong-chang|RC| Zhong|Nan-shan|NS|

impulse oscillometry
bronchiectasis
bacteriology
convalescence
acute exacerbation


Use of a primary care online consultation system, by whom, when and why: evaluation of a pilot observational study in 36 general practices in South West England.

Abstract:
OBJECTIVES
Evaluation of a pilot study of an online consultation system in primary care. We describe who used the system, when and why, and the National Health Service costs associated with its use.

DESIGN
15-month observational study.

SETTING
Primary care practices in South West England.

RESULTS
36 General practices covering 396 828 patients took part in the pilot. The online consultation website was viewed 35 981 times over the pilot period (mean 9.11 visits per 1000 patients per month). 7472 patients went on to complete an 'e-consultation' (mean 2.00 online consultations per 1000 patients per month). E-consultations were mainly performed on weekdays and during normal working hours. Patient records (n=485) were abstracted for eight practices and showed that women were more likely to use e-consultations than men (64.7% vs 35.3%) and users had a median age of 39 years (IQR 30-50). The most common reason for an e-consultation was an administrative request (eg, test results, letters and repeat prescriptions (22.5%)) followed by infections/immunological issues (14.4%). The majority of patients (65.2%) received a response within 2 days. The most common outcome was a face-to-face (38%) or telephone consultation (32%). The former were more often needed for patients consulting about new conditions (OR 1.56, 95% CI 1.05 to 2.27, p=0.049). The average cost of a practice's response to an e-consultation was £36.28, primarily triage time and resulting face-to-face/telephone consultations needed.

CONCLUSIONS
Use of e-consultations is very low, particularly at weekends. Unless this can be improved, any impact on staff workload and patient waiting times is likely to be negligible. It is possible that use of e-consultations increases primary care workload and costs. Online consultation systems could be developed to improve efficiency both for staff and patients. These findings have implications for software developers as well as primary care services and policy-makers who are considering investing in online consultation systems.

Edwards|Hannah B|HB|
Marques|Elsa|E|
Hollingworth|William|W|
Horwood|Jeremy|J|
Farr|Michelle|M|
Bernard|Elly|E|
Salisbury|Chris|C|
Northstone|Kate|K|

primary care
online consultations
evaluation
general practice
e-consultations


Comparing membrane and spacer biofouling by Gram-negative Pseudomonas aeruginosa and Gram-positive Anoxybacillus sp. in forward osmosis.

Abstract: Bacteria of different Gram-types have inherently different outer cell structures, influencing cell surface properties and bacterial attachment. Dynamic biofouling experiments were conducted over four days in a bench-scale forward osmosis (FO) system with Gram-negative Pseudomonas aeruginosa or Gram-positive Anoxybacillus sp. Biofouling resulted in ∼10% decline in FO permeate water flux and was found to be significant for Anoxybacillus sp. but not for P. aeruginosa. Additionally, a stronger permeate water flux decline for P. aeruginosa in experiments with a superhydrophilic feed spacer demonstrated that mitigation methods require testing with different bacterial Gram-types. It was found that although permeate water flux decline can be affected by bacterial Gram-type the stable performance under enhanced biofouling conditions highlights the potential of FO for wastewater reclamation.

Bogler|Anne|A| Rice|Douglas|D| Perreault|Francois|F| Bar-Zeev|Edo|E|

biofouling
Forward osmosis
wastewater
bacteria Gram-type
spacer modification


Improving Patient Safety by Reusing Clinical Routine Data - An Expert Survey on Patient Safety Indicators.

Abstract:
BACKGROUND
Patient safety is an important issue and receiving increasing attention. Information technology (IT) and IT-based strategies as the secondary use of already existing data within hospital information systems can help to improve patient safety.

OBJECTIVE
To investigate experts' knowledge and opinions regarding relevant patient safety problems, their measurability in existing clinical routine data and potential challenges in the field. We also wanted to get an overview of already deployed indicators for patient safety.

METHODS
Semi structured interviews with 20 experts from different healthcare domains were conducted and analyzed using a qualitative content analysis methodology.

RESULTS
The expert interviews offered a deeper insight into patient safety and quarried relevant patient safety problems including possibilities to measure them. The most often mentioned indicators were infection, complication and pressure ulcer.

CONCLUSION
From an experts' perspective there are several challenges but equally a high potential for improving patient safety by the use of health IT.

Schaller|Michael|M|
Hackl|Werner O|WO|
Ammenwerth|Elske|E|

D003695:Delivery of Health Care
D006751:Hospital Information Systems
D006801:Humans
D008490:Medical Informatics
D061214:Patient Safety
D011795:Surveys and Questionnaires

Patient Safety
Health Information Systems
Qualitative Research


Programmatic Assessment of Professionalism in Psychiatry Education: A Literature Review and Implementation Guide.

Abstract: Programmatic assessment is being adopted as a preferred method of assessment in postgraduate medical education in Australia. Programmatic assessment of professionalism is likely to receive increasing attention. This paper reviews the literature regarding the assessment of professionalism in psychiatry. A search using the terms 'professionalism AND psychiatry' was conducted in the ERIC database. Only original articles relevant to professionalism education and assessment in psychiatry were selected, rather than theoretical or review papers that applied research from other fields of medicine to psychiatry. Articles regarding the need for professionalism education in psychiatry were included as they provided a rationale for curriculum development in this field as a precursor to assessment. Key findings from the literature were summarised in light of the author's own experience as an educator and assessor of both medical students and trainees in psychiatry, and incorporated into a guide to implementing programmatic assessment of professionalism in psychiatry. Within psychiatry, the specific evidence base for use of particular tools in assessing professionalism is limited. However, used in conjunction with psychiatrists' views about what is important in professionalism education, as well as knowledge from other medical disciplines regarding professionalism assessment tools, this evidence can inform implementation of programmatic assessment of professionalism in undergraduate, postgraduate and continuing professional development settings. Given the emergent nature of such assessment initiatives, they should be subjected to rigorous evaluation.

Programmatic assessment
Professionalism
Psychiatry education
Medical education
Competency-based assessment


Graphene-Induced Hyperthermia (GIHT) Combined With Radiotherapy Fosters Immunogenic Cell Death.

Abstract: Radiotherapy and chemotherapy are the standard interventions for cancer patients, although cancer cells often develop radio- and/or chemoresistance. Hyperthermia reduces tumor resistance and induces immune responses resulting in a better prognosis. We have previously described a method to induce tumor cell death by local hyperthermia employing pegylated reduced graphene oxide nanosheets and near infrared light (graphene-induced hyperthermia, GIHT). The spatiotemporal exposure/release of heat shock proteins (HSP), high group mobility box 1 protein (HMGB1), and adenosine triphosphate (ATP) are reported key inducers of immunogenic cell death (ICD). We hypothesize that GIHT decisively contributes to induce ICD in irradiated melanoma B16F10 cells, especially in combination with radiotherapy. Therefore, we investigated the immunogenicity of GIHT alone or in combination with radiotherapy in melanoma B16F10 cells. Tumor cell death in vitro revealed features of apoptosis that is progressing fast into secondary necrosis. Both HSP70 and HMGB1/DNA complexes were detected 18 hours post GIHT treatment, whereas the simultaneous release of ATP and HMGB1/DNA was observed only 24 hours post combined treatment. We further confirmed the adjuvant potential of these released DAMPs by immunization/challenge experiments. The inoculation of supernatants of cells exposed to sole GIHT resulted in tumor growth at the site of inoculation. The immunization with cells exposed to sole radiotherapy rather fostered the growth of secondary tumors in vivo. Contrarily, a discreet reduction of secondary tumor volumes was observed in mice immunized with a single dose of cells and supernatants treated with the combination of GIHT and irradiation. We propose the simultaneous release of several DAMPs as a potential mechanism fostering anti-tumor immunity against previously irradiated cancer cells.

Podolska|Malgorzata J|MJ|
Shan|Xiaomei|X|
Janko|Christina|C|
Boukherroub|Rabah|R|
Gaipl|Udo S|US|
Szunerits|Sabine|S|
Frey|Benjamin|B|
Muñoz|Luis E|LE|

hyperthermia
radiotherapy
immunogenic cell death
reduced graphene oxide
melanoma
multimodal


Glucagon and/or IGF-1 Production Regulates Resetting of the Liver Circadian Clock in Response to a Protein or Amino Acid-only Diet.

Abstract: The circadian system controls the behavior and multiple physiological functions. In mammals, the suprachiasmatic nucleus (SCN) acts as the master pacemaker and regulates the circadian clocks of peripheral tissues. The SCN receives information regarding the light-dark cycle and is thus synchronized to the external 24-hour environment. In contrast, peripheral clocks, such as the liver clock, receive information from the SCN and other factors; in particular, food intake which leads to insulin secretion induces strong entrainment of the liver clock. On the other hand, the liver clock of insulin-depleted mice treated with streptozotocin (STZ) has been shown to be entrained by scheduled feeding, suggesting that insulin is not necessary for entrainment of the liver clock by feeding. In this study, we aimed to elucidate additional mechanism on entraining liver clock by feeding a protein-only diet and/or amino-acid administration which does not increase insulin levels. We demonstrated that protein-only diet and cysteine administration elicit entrainment of the liver clock via glucagon secretion and/or insulin-like growth factors (IGF-1) production. Our findings suggest that glucagon and/or IGF-1 production are additional key factors in food-induced entrainment.

Ikeda|Yuko|Y| Kamagata|Mayo|M| Hirao|Mizuho|M| Yasuda|Shinnosuke|S| Iwami|Shiho|S| Sasaki|Hiroyuki|H| Tsubosaka|Miku|M| Hattori|Yuta|Y| Todoh|Ai|A| Tamura|Konomi|K| Shiga|Kazuto|K| Ohtsu|Teiji|T| Shibata|Shigenobu|S|

Glucagon
IGF-1
Protein
Amino acid
Circadian rhythm
Food resetting


Relevance of interfacial viscoelasticity in stability and conformation of biomolecular organizates at air/fluid interface.

Abstract: Soft materials are complex macromolecular systems often exhibiting perplexing non-Newtonian viscoelastic properties, especially when the macromolecules are entangled, crowded or cross-linked. These materials are ubiquitous in the biology, food and pharma industry and have several applications in biotechnology and in the field of biosensors. Based on the length scales, topologies, flexibility and concentration, the systems behave both as liquids (viscous) and solids (elastic). Particularly, for proteins and protein-lipid systems, viscoelasticity is an important parameter because it often relates directly to stability and thermodynamic interactions of the pure biological components as well as their mixtures. Despite the large body of work that is available in solution macro-rheometry, there are still a number of issues that need to be addressed in dealing with proteins at air/fluid interfaces and with protein-polymer or protein-lipid interfaces that often exhibit very low interfacial viscosity values. Considering the important applications that they have in biopharmaceutical, biotechnological and nutraceutical industries, there is a need for developing methods that meet the following three specific issues: small volume, large dynamic range of shear rates and interfacial properties of different biomolecules. Further, the techniques that are developed should include Newtonian, shear thinning and yielding properties, which are representative of the different solution behaviors typically encountered. The review presented here is a comprehensive account of the rheological properties of different biomolecules at air/fluid and solid/fluid interfaces. It addresses the usefulness of 'viscoelasticity' of the systems at the interfaces analyzed at the molecular level that can be correlated with the microscopic material properties and touches upon some recent techniques in microrheology that are being used to measure the unusually low viscosity values sensitively.

Antony M|Steffi|S|
Jaganathan|Maheshkumar|M|
Dhathathreyan|Aruna|A|

D057927:Hydrophobic and Hydrophilic Interactions

Viscoelasticity
Conformation
Air/fluid interface
Colloidal dispersion
Interfacial rheology
Protein organizates


Advances in three-dimensional bioprinting of bone: Progress and challenges.

Abstract: Several attempts have been made to engineer a viable three-dimensional (3D) bone tissue equivalent using conventional tissue engineering strategies, but with limited clinical success. Using 3D bioprinting technology, scientists have developed functional prototypes of clinically relevant and mechanically robust bone with a functional bone marrow. Although the field is in its infancy, it has shown immense potential in the field of bone tissue engineering by re-establishing the 3D dynamic micro-environment of the native bone. Inspite of their in vitro success, maintaining the viability and differentiation potential of such cell-laden constructs overtime, and their subsequent preclinical testing in terms of stability, mechanical loading, immune responses, and osseointegrative potential still needs to be explored. Progress is slow due to several challenges such as but not limited to the choice of ink used for cell encapsulation, optimal cell source, bioprinting method suitable for replicating the heterogeneous tissues and organs, and so on. Here, we summarize the recent advancements in bioprinting of bone, their limitations, challenges, and strategies for future improvisations. The generated knowledge will provide deep insights on our current understanding of the cellular interactions with the hydrogel matrices and help to unravel new methodologies for facilitating precisely regulated stem cell behaviour.

bioprinting
bone
bone marrow
3D printing
bioink