Assessment of the effects of dysphagia therapy in patients in the early post-stroke period: a randomised controlled trial.

Abstract:
AIM
This study aimed to evaluate the effects of dysphagia therapy in patients in the early post-stroke period.

CLINICAL RATIONALE
Dysphagia can be one of the consequences of stroke. This problem often leads to complications in the early stages of stroke, including aspiration pneumonia. Although individual reports on dysphagia exist in the literature, no comprehensive guidelines for dysphagia therapy are available.

MATERIAL AND METHODS
This randomised controlled trial included 60 patients with swallowing difficulties after ischaemic stroke (30 each in the study and control groups; age range: 55-65 years) who were admitted to a hospital stroke subunit. Patient rehabilitation period covered 15 days (seven days a week), with therapy for the first 10 days provided during patient hospitalisation and then outpatient physiotherapy during the subsequent five days. The procedure, including providing education about safe food and liquid consumption to patients and their caregivers, was performed in both patient groups. An original dysphagia treatment method was employed in the study group. Statistical average, standard deviation, and statistical error before and after therapy were determined in the study and control groups. The significance of differences in results between the study and control groups was assessed using the Mann-Whitney U test.

RESULTS
The applied therapy for dysphagia improved the swallowing function and selected motor functions of patients after stroke. In the study group, ineffective (delayed) and absent swallowing reflex was observed in 13 patients (44%) before therapy and in one patient (3%) after therapy. The rate of effective swallowing reflex increased from 57% to 97%. Statistically significant differences in swallowing reflex were observed between the study and control groups after therapy (p = 0.00001).

CONCLUSIONS
A comprehensive therapy for dysphagia is effective and can reduce serious complications of swallowing disorders in clinical practice.

CLINICAL IMPLICATIONS
The results of this study could improve the clinical treatment of dysphagia.

Krajczy|Edyta|E| Krajczy|Marcin|M| Luniewski|Jacek|J| Bogacz|Katarzyna|K| Szczegielniak|Jan|J|

dysphagia stroke swallowing physiotherapy neurology


Validity and reliability of the Persian version of the nurse spiritual care therapeutics scale (NSCTS).

Abstract:
BACKGROUND
Dealing with the spiritual needs of patients has been recognized as one of the principles of holistic care in nursing. Therefore, it is necessary for nurses to deal with the spiritual issues of patients. Also, a valid and reliable scale is needed to measure nurse-provided spiritual care. So the purpose of this study was to determine the validity and reliability of the Persian version of the "Nurse Spiritual Care Therapeutics Scale" in Iranian nurses.

METHOD
In a methodological study, English version of the Nurse Spiritual Care Therapeutics Scale was translated into Persian by forward-backward translation procedure. Face validity was assessed by cognitive interview, and content validity was assessed by a panel of experts. In addition, construct validity was assessed by exploratory factor analysis. The participants were 188 nurses working in different adult wards. Reliability was measured using the Cronbach's alpha and stability reliability was assessed using the internal correlation coefficient (ICC).

RESULTS
In assessing the construct validity, two factors with eigenvalues greater than 1 were identified, which explained 58.47% of the total variance. Cronbach's alpha value was 0.932, and ICC was 0.892.

CONCLUSION
As a result, the Persian version of the Nurse Spiritual Care Therapeutics Scale shows a good validity and reliability. Therefore, this scale can be used to evaluate spiritual care at the bedside in Iran.

Merati-Fashi|Fatemeh|F| Khaledi-Paveh|Behnam|B| Mosafer|Hadis|H| Ebadi|Abbas|A|

Validity
Reliability
Persian
Nurse
Spiritual care


Focal adhesion kinase regulates tractional collagen remodeling, matrix metalloproteinase expression, and collagen structure, which in turn affects matrix-induced signaling.

Abstract: Focal adhesion kinase (FAK) is critical for collagen expression but its regulation of collagen remodeling is not defined. We examined the role of FAK in the degradation and reorganization of fibrillar collagen. Compared with wild-type (WT) mouse embryonic fibroblasts, FAK null (FAK-/- ) fibroblasts generated twofold (p < .0001) higher levels of ¾ collagen I fragment and expressed up to fivefold more membrane-type matrix metalloproteinase (MMP). When plated on stiff collagen substrates, compared with WT, FAK-/- cells were smaller (threefold reduced cell surface area; p < .0001) and produced fivefold fewer cell extensions (p < .0001) that were 40% shorter (p < .001). When cultured on soft collagen gels (stiffness of ~100 Pa) for 6-48 hr, cell spreading and cell extension formation were reduced by greater than twofold (p < .05 and p < .0001, respectively) while collagen compaction and alignment were reduced by approximately 30% (p < .0001) in FAK-/- cells. Similar results were found after treatment with PF573228, a FAK inhibitor. Reconstitution of FAK-/- cells with FAK mutants showed that compared with WT, cell extension formation was reduced twofold (p < .0001) in the absence of the kinase domain and sixfold (p < .0001) with a Y397F mutant. Enhanced collagen degradation was exhibited by the mutants (~threefold increase; p < .0001 of ¾ collagen fragments without kinase domain or Y397F mutant; p < .01). Compared with FAK+/+ cells, matrices produced by FAK-/- cells generated higher levels of β1 integrin activation (p < 0.05), extracellular-signal-regulated kinase (ERK) phosphorylation, and production of ¾ collagen I fragment by human gingival fibroblasts. Collectively these data indicate that (a) the kinase activity of FAK enhances collagen remodeling by tractional forces but inhibits collagen degradation by MMPs; (b) FAK influences the biological activity of fibroblast-secreted extracellular matrices, which in turn impacts β1 integrin and ERK signaling, and collagen degradation.

D048049:Extracellular Signal-Regulated MAP Kinases

D051416:Focal Adhesion Protein-Tyrosine Kinases

focal adhesion kinase
collagen
matrix-signaling


Brain-derived neurotrophic factor and schizophrenia.

Abstract: Schizophrenia is a severe disorder affecting approximately 1% of the population. Historically, alterations of dopaminergic function were considered the primary cause of schizophrenia. However, for many patients, drugs that alter dopaminergic function do not consistently lead to resolution of the symptoms of schizophrenia. Thus, there is an increased interest in pathophysiologic processes that result in altered neurodevelopment and plasticity associated with schizophrenia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis, synaptic plasticity, cognition, and neurotransmission. Genetic polymorphism, expression, and function of BDNF have been implicated in psychiatric diseases, including schizophrenia. This review discusses BDNF, its role in neurologic processes, and the evidence implicating BDNF in schizophrenia.

brain-derived neurotrophic factor
schizophrenia
BDNF


Non-transport after Prehospital Naloxone Administration Is Associated with Higher Risk of Subsequent Non-fatal Overdose.

Abstract: Objective: U.S. opioid overdoses increased nearly sixfold from 1999 to 2018, and greater than 1% of all emergency medical services (EMS) encounters now involve naloxone administration. While "treat and release" protocols may have low short-term mortality, the risk of subsequent non-fatal overdoses is not known. This study compares the risk of repeat overdose encounters between patients transported to an emergency department (ED) and those who refused transport after prehospital naloxone administration. Methods: All EMS charts within a large single-tier fire-based urban EMS system between January 1 and August 31, 2018 were reviewed if either naloxone administration or a clinical impression related to opioid overdose was documented. Charts were excluded if there was no documented evidence of an opioid toxidrome (respiratory depression or altered mental status), if there was another clear explanation for the symptoms (e.g., hypoglycemia), or if naloxone was not administered. Ten percent of charts were reviewed by a second author to assess reliability. Cox regression (survival analysis) was used to estimate the risk of a subsequent EMS encounter with naloxone administration following an index encounter with naloxone administration. Results: Of the 2143 charts reviewed, 1311 unique patients with 1600 overdose encounters involving naloxone administration were identified. Inter-rater reliability for chart inclusion was strong [κ = 0.83 (95% CI: 0.72-0.90)]. Police/bystanders administered naloxone in 208/1600 (13.0%) encounters. A substantial proportion of encounters resulted in transport refusal (674/1600, 42.1%). The final Cox model included only refusal vs. acceptance of transport to an ED during the index EMS encounter. Patient age, gender, and naloxone administration prior to EMS arrival were not statistically significant in univariate or multivariable analyses, nor were they significant confounders. Refusal of transport was associated with a hazard ratio of 1.66 (95% CI: 1.23-2.23) for subsequent EMS encounters with naloxone administration. Conclusions: Non-transport after prehospital naloxone administration is associated with an increased risk of subsequent non-fatal overdose requiring EMS intervention. Limitations include the use of a single EMS agency as patients may have had uncaptured overdose encounters in neighboring municipalities.

naloxone
EMS
drug overdose
treatment refusal


Epidemiology of Maxillofacial Traumatisms in French Alps Metropole (Grenoble) Specificity for the mountain sports and evolution in the last 40 years.

Abstract:
INTRODUCTION
Over the years, several studies have been carried in the Teaching Hospital of Grenoble, analysing the epidemiology of facial injuries. The aim of this study was to gather and compare the previous works, focusing on the injuries caused by mountains sports. The evolution of mountain sports trauma in the last 40 years was studied, and observations on the protective action on the face and facial bones of the helmet were made.

MATERIALS AND METHODS
The data from all facial injuries treated in the years 2016 and 2017 were collected, and a retrospective study was performed. It was supplemented by the data of 3 articles (1981, 1992, 2006) and a thesis (1985).

RESULTS
Localizations of the fractures, when not discriminated according to causes, were consistently the same in our study than in previous works, with 66% of upper 2/3 of the face fractures, and 22% of lower 1/3 fractures. When filtering only mountain sports traumatisms, a significant decrease of upper 2/3 facial injuries was observed in the current study compared to the 1981, 1985 and 2006 data. This drop tallies with the period where the use of the helmet generalized. The evolution of mountain sports practices, the improvement of protective personal equipment and of the security on sport sites triggered a real diminution of mid and upper face traumatisms.

Gelin|Sophie Pia|SP|
Giot|Jean Philippe|JP|

Mountain sport
Helmet
Facial fracture
Facial traumatism
Ski


Boron oxynitride two-colour fluorescent dots and their incorporation in a hybrid organic-inorganic film.

Abstract: Bottom-up synthesis of fluorescent boron-nitride based dots is a challenging task because an accurate design of the structure-properties relationship is, in general, difficult to achieve. Incorporation of the dots into a solid-state matrix is also another important target to develop light-emitting devices. Two-colour fluorescent boron oxynitride nanodots have been obtained by a bottom-up synthesis route and incorporated into a hybrid organic-inorganic film. A combination of different analytical techniques such as XPS, XRD, TEM, UV-Vis, TGA-DTA and fluorescence has been used to characterise the structure, composition and properties of the boron oxynitride dots. The presence of defects in the boron oxynitride structure is the source of the two-colour fluorescence. The BN dots thermal stability is limited to around 100 °C; higher temperatures induce condensation of the structure, which leads to a lower emission. Upon incorporation into a hybrid organic-inorganic film deposited by spin-coating, the boron oxynitride dots maintain their fluorescence and have shown to be highly compatible with the sol-gel chemistry.

Ren|Junkai|J|
Malfatti|Luca|L|
Enzo|Stefano|S|
Carbonaro|Carlo Maria|CM|
Calvillo|Laura|L|
Granozzi|Gaetano|G|
Innocenzi|Plinio|P|

Boron oxynitride
Sol-gel
Fluorescent materials
Quantum dots
Thin films


Fast Assembly of Gold Nanoparticles in Large-Area 2D Nanogrids Using a One-Step, Near-Infrared Radiation-Assisted Evaporation Process.

Abstract: When fabricating photonic crystals from suspensions in volatile liquids using the horizontal deposition method, the conventional approach is to evaporate slowly to increase the time for particles to settle in an ordered, periodic close-packed structure. Here, we show that the greatest ordering of 10 nm aqueous gold nanoparticles (AuNPs) in a template of larger spherical polymer particles (mean diameter of 338 nm) is achieved with very fast water evaporation rates obtained with near-infrared radiative heating. Fabrication of arrays over areas of a few cm(2) takes only 7 min. The assembly process requires that the evaporation rate is fast relative to the particles' Brownian diffusion. Then a two-dimensional colloidal crystal forms at the falling surface, which acts as a sieve through which the AuNPs pass, according to our Langevin dynamics computer simulations. With sufficiently fast evaporation rates, we create a hybrid structure consisting of a two-dimensional AuNP nanoarray (or "nanogrid") on top of a three-dimensional polymer opal. The process is simple, fast, and one-step. The interplay between the optical response of the plasmonic Au nanoarray and the microstructuring of the photonic opal results in unusual optical spectra with two extinction peaks, which are analyzed via finite-difference time-domain method simulations. Comparison between experimental and modeling results reveals a strong interplay of plasmonic modes and collective photonic effects, including the formation of a high-order stopband and slow-light-enhanced plasmonic absorption. The structures, and hence their optical signatures, are tuned by adjusting the evaporation rate via the infrared power density.

Utgenannt|André|A|
Maspero|Ross|R|
Fortini|Andrea|A|
Turner|Rebecca|R|
Florescu|Marian|M|
Jeynes|Christopher|C|
Kanaras|Antonios G|AG|
Muskens|Otto L|OL|
Sear|Richard P|RP|
Keddie|Joseph L|JL|

gold nanoparticles
evaporation
photonics
plasmonics
IR heating
coupling
inverse opal
self-assembly


Reproductive interference by male Drosophila subobscura on female D. persimilis: A laboratory experiment.

Abstract: While females often reject courtship attempts by heterospecific males, reproductive interference by harassment from such males can nonetheless occur, potentially reducing female fitness. Such effects may be profound following a range expansion, when males from a new species may suddenly encounter (and perhaps even become abundant relative to) females of related native species. Drosophila subobscura recently invaded North America and may impact native species through reproductive interference and other processes. We test for the potential for reproductive interference by D. subobscura males on D. persimilis females in the laboratory. D. subobscura males aggressively copulated with D. persimilis females, including many females that exhibit rejection behaviors. Despite females attempting to dismount the males, the heterospecific copulations are on average longer than conspecific copulations, and females exhibit some reluctance to remate with conspecific males following this harassment. Females confined with both conspecific and heterospecific males produce fewer adult progeny than those with either conspecific males only or with conspecific males and distantly related D. simulans males that do not engage in female harassment. Overall, our results illustrate how reproductive interference by an invasive species can have negative effects on resident natural populations.

Manzano-Winkler|Brenda|B|
Hish|Alexander J|AJ|
Aarons|Emily K|EK|
Noor|Mohamed A F|MA|0000-0002-5400-4408

reproductive interference
Drosophila subobscura
invasive species
Drosophila persimilis


Oxidized LDL, statin use, morbidity, and mortality in patients receiving maintenance hemodialysis.

Abstract: Statin treatment reduces the risk of cardiovascular mortality in the general population, but it has little or no benefit in hemodialyzed (HD) patients. This may reflect different underlying pathophysiology of cardiovascular disease (CVD) in patients treated with HD, maybe involving the oxidative stress. Our aim was to assess the association of oxidized low-density lipoprotein (oxLDL), determined by Mercodia oxLDL enzyme-linked immunosorbent assay (ELISA) kit, with major adverse cardiac events (MACE) and all-cause mortality in HD patients based on the AURORA trial (rosuvastatin vs placebo), and patients not on HD from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We also assessed whether its decrease due to statin use improves these outcomes using Cox proportional hazard models. Baseline oxLDL level was 34.2 ± 13.8 U/L in AURORA and did not differ between treatment groups, and 74.6 ± 28.1 U/L in LURIC. Lower baseline oxLDL levels were associated with higher hazard ratios (HRs) for outcomes, but not anymore after adjusting for apolipoprotein B level in AURORA and was not related to mortality in LURIC. OxLDL levels decreased by 30.9% between baseline and 3 months in the statin-treated group and increased by 10.5% between 3 and 12 months. Nevertheless, oxLDL reduction was not significantly associated with adjusted HRs for MACE and for all-cause mortality. These results showed no association between oxLDL and MACE after adjustment on apolipoprotein B, which may relate to the properties of the method used for oxLDL. Our results also showed no benefit for oxLDL reduction by rosuvastatin on outcomes. Future clinical trials are needed to define the relative CVD risks and benefits of other modalities of oxidative stress modification in this population.

Wagner|Sandra|S|
Apetrii|Mugurel|M|
Massy|Ziad A|ZA|
Kleber|Marcus E|ME|
Delgado|Graciela E|GE|
Scharnagel|Hubert|H|
März|Winfried|W|
Metzger|Marie|M|
Rossignol|Patrick|P|
Jardine|Alan|A|
Holdaas|Hallvard|H|
Fellström|Bengt|B|
Schmieder|Roland|R|
Stengel|Bénédicte|B|
Zannad|Faiez|F|
|||

Oxidized LDL
statin
mortality
cardiovascular risks
hemodialyzed patients


Permanent caries experience is associated with primary caries experience: a 7-year longitudinal study in China.

Abstract:
OBJECTIVES
The aim of this study was to evaluate the association between caries experience in primary teeth and caries experience in permanent teeth in a longitudinal study.

METHODS
Teeth were examined at 5 years of age and a follow-up examination was conducted 7 years later at 12 years of age in all children from Jiading District, Shanghai, China. A total of 1885 participants were recruited in the study; 1683 students were followed up and 202 students (10.7%) were lost to follow up. Data were analyzed using the chi-square test, t-test and risk ratio.

RESULTS
The followed-up samples comprised 883 boys (52.5%) and 800 girls (47.5%). At initial examination, the prevalence of dental caries was 67.4% in boys and 66.5% in girls (χ² = 0.2, P = 0.70), with mean decayed, missing and filled teeth (dmft) scores of 3.5 ± 0.1 and 3.4 ± 0.1, respectively (t = 0.1, P = 0.90). At follow-up, the prevalence of dental caries was 33.9% in boys and 37.9% in girls (χ² = 2.9, P = 0.11), with mean DMFT scores in permanent teeth of 0.7 ± 0.0 and 0.8 ± 0.1, respectively (t = 1.2, P = 0.24). The group of 5-year-olds with caries had a significantly higher prevalence of caries in permanent teeth (45.5%) at 12 years of age than the group of 5-year-olds without caries (16.0%) (χ2 = 141.1, P < 0.001, risk ratio = 1.5). Caries risk in permanent teeth was significantly higher with greater dmft scores (χ2 for trend = 31.1, P < 0.001).

CONCLUSIONS
Caries in primary teeth is a major risk factor for caries in permanent teeth. The likelihood of caries in permanent teeth is higher with greater dmft scores in primary teeth.

Du|Qin|Q| Yu|Ming|M| Li|Yueling|Y| Du|Haojing|H| Gao|Wenlan|W| Mei|Hao|H| Liu|Shijian|S|

longitudinal study
primary teeth
permanent teeth
dental caries
Chinese children


Quantitative Comparison of UAS-Borne LiDAR Systems for High-Resolution Forested Wetland Mapping.

Abstract: Wetlands provide critical ecosystem services across a range of environmental gradients and are at heightened risk of degradation from anthropogenic pressures and continued development, especially in coastal regions. There is a growing need for high-resolution (spatially and temporally) habitat identification and precise delineation of wetlands across a variety of stakeholder groups, including wetlands loss mitigation programs. Traditional wetland delineations are costly, time-intensive and can physically degrade the systems that are being surveyed, while aerial surveys are relatively fast and relatively unobtrusive. To assess the efficacy and feasibility of using two variable-cost LiDAR sensors mounted on a commercial hexacopter unmanned aerial system (UAS) in deriving high resolution topography, we conducted nearly concomitant flights over a site located in the Atlantic Coastal plain that contains a mix of palustrine forested wetlands, upland coniferous forest, upland grass and bare ground/dirt roads. We compared point clouds and derived topographic metrics acquired using the Quanergy M8 and the Velodyne HDL-32E LiDAR sensors with airborne LiDAR and results showed that the less expensive and lighter payload sensor outperforms the more expensive one in deriving high resolution, high accuracy ground elevation measurements under a range of canopy cover densities and for metrics of point cloud density and digital terrain computed both globally and locally using variable size tessellations. The mean point cloud density was not significantly different between wetland and non-wetland areas, but the two sensors were significantly different by wetland/non-wetland type. Ultra-high-resolution LiDAR-derived topography models can fill evolving wetlands mapping needs and increase accuracy and efficiency of detection and prediction of sensitive wetland ecosystems, especially for heavily forested coastal wetland systems.

LiDAR
mapping
wetlands delineation
Unmanned aerial systems
UAS
topographic modeling


Intergenerational Association of Short Maternal Stature with Stunting in Yanomami Indigenous Children from the Brazilian Amazon.

Abstract: To describe the factors associated to stunting in <5-year-old Yanomami Brazilian children, and to evaluate the association of short maternal stature to their offspring's stunting. A cross-sectional study carried out in three villages in the Yanomami territory. We performed a census, in which all households with children < 5-years-old were included. The length/height-for-age z-score <-2 standard deviations was used to classify the children as stunted. Short maternal height was defined as <145 cm for adult women, and <-2 standard deviations of the height-for-age z-score for adolescent women. We used adjusted Poisson regression models to estimate prevalence ratios (PR) along the 90% confidence interval. We evaluated 298 children. 81.2% of children suffered from stunting and 71.9% of the mothers from short stature. In the bivariate analysis, a significant association of stunting with short maternal stature, gestational malaria and child's place of birth were observed. Considering the variables of the children under five years of age, there were significant associations with age group, the child's caregiver, history of malaria, pneumonia, and malnutrition treatment. In the adjusted hierarchical model, stunting was 1.22 times greater in the offspring of women with a short stature (90% CI: 1.07-1.38) compared to their counterparts. Brazilian Amazonian indigenous children living in a remote area displayed an alarming prevalence of stunting, and this was associated with short maternal height, reinforcing the hypothesis of intergenerational chronic malnutrition transmission in this population. In addition, children above 24 months of age, who were born in the village healthcare units and who had had previous treatment in the past for stunting presented higher rates of stunting in this study.

de Vasconcellos|Ana Claudia Santiago|ACS|

epidemiologic determinants
indigenous populations
intergenerational relations
poverty areas
undernutrition


The role of advocacy coalitions in a project implementation process: the example of the planning phase of the At Home/Chez Soi project dealing with homelessness in Montreal.

Abstract: This study analyzed the planning process (summer 2008 to fall 2009) of a Montreal project that offers housing and community follow-up to homeless people with mental disorders, with or without substance abuse disorders. With the help of the Advocacy Coalition Framework (ACF), advocacy groups that were able to navigate a complex intervention implementation process were identified. In all, 25 people involved in the Montreal At Home/Chez Soi project were surveyed through interviews (n=18) and a discussion group (n=7). Participant observations and documentation (minutes and correspondence) were also used for the analysis. The start-up phase of the At Home/Chez may be broken down into three separate periods qualified respectively as "honeymoon;" "clash of cultures;" and "acceptance & commitment". In each of the planning phases of the At Home/Chez Soi project in Montreal, at least two advocacy coalitions were in confrontation about their specific belief systems concerning solutions to address the recurring homelessness social problem, while a third, more moderate one contributed in rallying most key actors under specified secondary aspects. The study confirms the importance of policy brokers in achieving compromises acceptable to all advocacy coalitions.

Fleury|Marie-Josée|MJ| Grenier|Guy|G| Vallée|Catherine|C| Hurtubise|Roch|R| Lévesque|Paul-André|PA|

D002170:Canada
D003254:Consumer Advocacy
D003299:Cooperative Behavior
D006703:Homeless Persons
D006798:Housing
D006801:Humans
D007373:Interinstitutional Relations
D001523:Mental Disorders
D015397:Program Evaluation
D036301:Qualitative Research
D019966:Substance-Related Disorders

Coalitions
Implementation process
Homelessness
Mental health


Fluorescent "Turn-on" Sensing Based on Metal-Organic Frameworks (MOFs).

Abstract: Metal-organic frameworks (MOFs) have evolved as an exciting class of materials in the domain of porous materials. The unique features of these materials arise from the combined properties of metal ions/clusters and organic struts which form the building blocks of these fascinating architectures. Among other multifarious applications, MOFs have shown tremendous applications as sensory materials for a wide variety of species. The signal transduction induced mechanism in these confined nanospaces generate optical output in response to a particular analyte which can be detected by wide variety of detection techniques. Fluorometric methods of sensing is one of widely studied method over past few decades. MOF-based fluorometric detection is a key research theme developed over the past few years. In this review, we give a brief overview of the recent developments of MOFs as "turn-on" sensors for a wide range of analytes (viz. cations, anions, volatile organic compounds (VOCs), etc.).

Sensing
Metal-organic frameworks
Luminescence
Porous coordination polymers
Turn-on sensors


Rethinking the Importance of the Individual within a Community of Data.

Abstract: The Covid-19 crisis has underscored the importance of the collection and analysis of clinical and research data and specimens for ongoing work. The federal government recently completed a related revision of the human subjects research regulations, founded in the traditional principles of research ethics, but in this commentary, we argue that the analysis underpinning this revision overemphasized the importance of informed consent, given the low risks of secondary research. Governing the interests of a community is different from governing the interests of individuals, and here we suggest that, moving forward, the analyses of the risks of secondary research protocols be assessed from the perspective of the former.

D035843:Biomedical Research
D000086382:COVID-19
D028744:Ethics Committees, Research
D035082:Federal Government
D033161:Government Regulation
D006805:Human Experimentation
D006801:Humans
D007258:Informed Consent
D011050:Policy Making
D012107:Research Design
D035842:Research Subjects


Sarilumab versus standard of care for the early treatment of COVID-19 pneumonia in hospitalized patients: SARTRE: a structured summary of a study protocol for a randomised controlled trial.

Abstract:
OBJECTIVES
In some patients, acute, life-threatening respiratory injury produced by viruses such as SARS-CoV and other viral pneumonia are associated with an over-exuberant cytokine release. Elevated levels of blood IL-6 had been identified as a one of the risk factors associated with severe COVID-19 disease. Anti-IL6 inhibitors are among the therapeutic armamentarium for preventing the fatal consequences of acute respiratory and multi organ failure in around 20% of the COVID-19 infected patients. At present, their use is prioritized to patients with severe interstitial pneumonia (Brescia-COVID Scale-COVID 2-3) with hyperinflammation as determined by the presence of elevated IL6 and/or d-dimer, or progressive d-dimer increase, in patients who otherwise are subsidiary to ICU admission. However, many uncertainties remain on the actual role of anti-IL6 inhibitors in this setting, and whether current use and timing is the right one. There is the hypothesis that the use of anti-IL6 inhibitors at an earlier state during the hyperinflammatory syndrome would be beneficial and may avoid progressing to ARDS. On the other hand, the standard of care has changed and nowadays the use of corticosteroids has become part of the SOC in the treatment of COVID-19 pneumonia. Our limited experience suggests that better treatment outcomes can be achieved when combining IL6-inhibitors (e.g. sarilumab) with corticosteroids. The aim of the present study is to evaluate if an earlier therapeutic intervention with sarilumab plus SOC (including corticosteroids) may be more effective than current standard of care alone, in preventing progression to respiratory failure in COVID-19 infected patients with interstitial pneumonia. This study will also provide supportive evidence to that provided by currently ongoing studies on the efficacy and safety of sarilumab in this clinical context.

TRIAL DESIGN
A phase two multi-center randomised controlled trial (RCT) with two parallel arms (1:1 ratio).

PARTICIPANTS
They will be hospitalized patients, of at least 18 years of age, with severe COVID-19 who have positive RT-PCR test and have radiographic evidence of pulmonary infiltrates by imaging or rales/crackles on exam and SpO2 ≤ 94% on room air that requires supplemental oxygen. Patients must present elevation of inflammatory parameters (IL-6 > 40 pg/mL or d-dimer >1.0 mcg/ml) or, alternatively, progressive worsening in at least two of these inflammatory parameters in the prior 24-48h: CRP, LDH, serum ferritin, lymphopenia, or d-dimer.

EXCLUSION CRITERIA
high oxygen requirements (including face mask with reservoir, non-invasive mechanical ventilation or high flow nasal cannula, or mechanical ventilation), admission to ICU, pregnancy or lactation, allergy or hypersensitivity to sarilumab or corticoesteroids, immunosuppressive antibody therapy within the past 5 months, AST/ALT values > 10 x ULN, neutropenia (< 0.5 x 109/L), severe thrombocytopenia (< 50 x 109/L), sepsis caused by an alternative pathogen, diverticulitis with risk of perforation or ongoing infectious dermatitis. The study will be conducted in several hospitals in Spain.

INTERVENTION AND COMPARATOR
Patients randomised to the experimental arm will receive sarilumab + methylprednisolone plus SOC for COVID-19. Patients included in the control arm will receive methylprednisolone plus SOC for COVID-19. Corticosteroids will be given to all patients at a 1mg/kg/d of methylprednisolone for at least 3 days. Clinical follow-up visits will be performed at 3, 5, and 15 days after treatment randomization. Patients in the control group (SOC group without sarilumab) progressing to Brescia- COVID 2-3 plus inflammatory markers, will be given the option to be rescued with sarilumab at the same doses and, in that case, be included in an open-label phase and be followed up for additional weeks (with visits at 3, 7 and 15 days after sarilumab rescue administration). Patients randomly assigned to sarilumab therapy at baseline progressing to Brescia-COVID 2-3 will be rescued according to local clinical practice protocols. A final follow-up visit will be conducted for all patients at day 29 from randomization, regardless of initial treatment assignment.

MAIN OUTCOMES
Primary end point is the proportion of patients progressing to either severe respiratory failure (Brescia-COVID ≥2), ICU admission, or death.

RANDOMIZATION
Randomization codes were produced by means of the PROC PLAN of the SAS system, with a 1:1 assignment ratio, stratifying by centre and using blocks multiple of 2 elements. The randomization schedule will be managed through the eCRF in a concealed manner.

BLINDING (MASKING)
All study drugs will be administered as open label. No blinding methods will be used in this trial.

NUMBERS TO BE RANDOMISED (SIMPLE SIZE)
The target sample size will be 200 COVID-19 patients, who will be allocated randomly to control arm (100) and treatment arm (100).

TRIAL STATUS
Protocol Code: SARTRE Protocol Date: May 05th 2020. Version: 2.0 The study has been approved by the Spanish Competent Authority (AEMPS) as a low intervention clinical trial. Start of recruitment: August, 2020 End of recruitment: May, 2021 TRIAL REGISTRATION: Identifier: EudraCT Number: 2020-002037-15 ; Registration date: 26 May 2020.

FULL PROTOCOL
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

D017322:Clinical Trials, Phase II as Topic

D016032:Randomized Controlled Trials as Topic

sarilumab
COVID-19
protocol
Randomised controlled trial
anti-IL6 inhibitor
severe interstitial pneumonia
corticosteroids
SARS-CoV-2
early intervention


Plasminogen Activator Inhibitor 1 Promotes Immunosuppression in Human Non-Small Cell Lung Cancers by Enhancing TGF-Β1 Expression in Macrophage.

Abstract:
BACKGROUND
Plasminogen activator inhibitor-1 (PAI-1) has been regarded as a risk factor for thrombosis and atherosclerosis. Since it has been shown that PAI-1 can activate macrophages through Toll-like receptor-4, we sought to investigate the role of PAI-1 in the tumor microenvironment.

METHODS
The expression and distribution patterns of PAI-1 and transforming growth factor beta (TGF-β) were measured in 60 non-small cell lung cancer (NSCLC) tumors. A statistical correlation analysis was performed between PAI-1 and TGF-β expression and distribution in each tumor. The distribution of tumor-associated macrophages (TAMs) was also measured and its correlation to PAI-1 levels was analyzed. Levels of secreted CCL-17, CCL-22, IL-6 and TGF-β were measured in cell cultures of human macrophage cell lines THP-1 and U937 treated with PAI-1. Levels of secreted PAI-1 were monitored in cell cultures of human NSCLCs cell lines 95D and A549 treated with TGF-β. Secreted proteins were measured in cell culture supernatants using ELISA. Changes in downstream signaling pathways were investigated using western blot.

RESULTS
PAI-1 and TGF-β were found to be overexpressed in human NSCLCs. PAI-1 expression was tightly correlated to TGF-β expression as well as the percentage of TAMs. PAI-1 treatment increased the expression of TAM-associated cytokines and chemokines, including CCL-17, CCL-22, and IL-6. PAI-1 treatment was also observed to enhance TGF-β expression in macrophage cell lines through an IL-6 autocrine/paracrine manner. The effects on TGF-β expression were blocked by NF-κB and STAT3 inhibition. Interestingly, TGF-β also increased levels of secreted PAI-1 in NSCLC cells through SMAD3-dependent signaling, therefore resulting in a feed-forward loop. However, this loop could be blocked by NF-κB, STAT3 and SMAD3 signaling inhibition, as well as treatment with a high concentration of TGF-β.

CONCLUSION
PAI-1 and TGF-β promote NSCLC tumor cells and TAMs and might be valuable targets for cancer immunosuppression.

Zhu|Chengjun|C| Shen|Hua|H| Zhu|Lingjun|L| Zhao|Feng|F| Shu|Yongqian|Y|

D017395:Plasminogen Activator Inhibitor 1

D053773:Transforming Growth Factor beta1


Unusual and delayed presentation of chronic uterine inversion in a young woman as a result of negligence by an untrained birth attendant: a case report.

Abstract:
BACKGROUND
Uterine inversion is a rare but known complication following parturition and may prove fatal due to neurogenic shock or postpartum hemorrhage if not corrected immediately. The incidence is variable, occurring in 1 in 2000 to 1 in 50,000 deliveries, as reported in the past. Nowadays, the incidence is declining due to better antenatal care and increasing institutional deliveries. However, in a developing country such as India, due to cultural and financial reasons, most of the deliveries are still being conducted by untrained birth attendants ("dais") who have sparse knowledge of oxytocic drugs. Hence, proper education and training should be imparted to the traditional birth attendants and local village health practitioners about the management of labor, placental delivery, timely diagnosis, and proper management of uterine inversion to avoid this grave complication. We report this case because only a limited number of such cases have been reported so far with delayed presentation of chronic uterine inversion 8 months after delivery as a result of the negligence of an untrained birth attendant.

CASE PRESENTATION
We report a case of a patient with chronic uterine inversion presenting 8 months after childbirth as a result of ignorance at the time of delivery. A 22-year-old P1L1 (Para 1 Live 1) Asian woman of Punjabi ethnicity presented to our institute with a progressively increasing painless vaginal mass along with blood-stained vaginal discharge for the last 6 months and progressive dyspareunia (pain during intercourse) for the last 5 months that had worsened with time. She had experienced a full-term normal vaginal delivery at home 8 months earlier with the assistance of an untrained birth attendant (dai). Her history revealed that she had an unduly prolonged second stage of labor and was given aggressive fundal pressure due to inadequate bearing-down efforts and had collapsed after delivery but was managed conservatively by an untrained birth attendant. A provisional diagnosis of chronic uterine inversion was made on the basis of vaginal findings of a globular mass protruding from the cervix and approaching the vagina with thinning of the cervix around the mass, forming a tight constriction ring, in addition to ultrasound findings. The patient's condition was corrected surgically using Haultain's approach. She had a satisfactory outcome and was discharged symptom-free.

CONCLUSION
Awareness of this complication with timely diagnosis and prompt management can significantly minimize maternal morbidity and mortality, especially in a low- and middle-income country such as India, where 70-80% of deliveries still occur in a rural setting with untrained birth attendants.

Chronic uterine inversion
Parturition
Postpartum hemorrhage
Haultain’s method


Ginseng increases Klotho expression by FoxO3-mediated manganese superoxide dismutase in a mouse model of tacrolimus-induced renal injury.

Abstract: The antioxidant function of Klotho is well-documented as a regulatory factor implicated in countering the aging process. This study investigated whether ginseng upregulates Klotho and its antiaging signaling in a setting of calcineurin inhibitor-induced oxidative stress. Although tacrolimus treatment reduced Klotho level in the serum and kidney, ginseng treatment was found to reverse the levels. Tacrolimus-induced oxidative stress was reduced by ginseng treatment, with functional and histological improvements. Effect of ginseng on Klotho-induced manganese superoxide dismutase signaling pathway during tacrolimus treatment in mice revealed that ginseng suppressed phosphatidylinositol 3-kinase/serine-threonine kinase Akt-mediated phosphorylation of forkhead box protein O3a and promoted the binding of forkhead box protein O3a to manganese superoxide dismutase promoter. In the mitochondria, ginseng reduced mitochondrial reactive oxygen species production, mitochondrial membrane potential, and oxygen consumption rate, whereas blocking phosphatidylinositol 3-kinase activity with LY294002 enhanced them. These findings together suggested that ginseng attenuated tacrolimus-induced oxidative stress via signaling between Klotho and the phosphatidylinositol 3-kinase/serine-threonine kinase Akt/forkhead box protein O3a-related antioxidant pathway.

Lim|Sun Woo|SW|
Shin|Yoo Jin|YJ|
Luo|Kang|K|
Quan|Yi|Y|
Cui|Sheng|S|
Ko|Eun Jeong|EJ|
Chung|Byung Ha|BH|
Yang|Chul Woo|CW|

ginseng
Klotho
oxidative stress
tacrolimus
mitochondria
MnSOD


Neurocognitive functioning in pediatric craniopharyngioma: performance before treatment with proton therapy.

Abstract: The goal of this study was to investigate the impact of patient-, disease-, and treatment-related variables upon neurocognitive outcomes in pediatric patients with craniopharyngioma prior to treatment with proton therapy or observation after radical resection. For all participants (N = 104), relevant clinical and demographic variables were attained and neurocognitive evaluations completed prior to irradiation or planned observation. One-sample t-tests were conducted to compare performance to published normative data. Linear models were used to investigate predictors of performance on measures where performance was below normative expectations. Participants showed poorer performance in comparison to the normative group across neurocognitive domains including executive functions (e.g., working memory; Wechsler Digit Span Backward p = 0.03), learning and memory (e.g., California Verbal Learning Test [CVLT] Total T p = 0.00), and fine-motor coordination (e.g., Grooved Pegboard Dominant Hand p = 0.00). Poor performance across areas was predicted by presurgical hypothalamic involvement (e.g., Behavior Rating Inventory of Executive Function Working Memory Index Grade 2 β = -7.68, p = 0.03; CVLT Total T Grade 2 β = 7.94, p = 0.04; Grade 3 β = -9.80, p = 0.00), extent of surgery (e.g., CVLT Total T Resection β = -7.77, p = 0.04; Grooved Pegboard Dominant Hand β = -1.58, p = 0.04), and vision status (e.g., CVLT Total T Reduced vision without impairment β = -10.01, p = 0.02; Grooved Pegboard Dominant Hand Bilateral field defect β = -1.45, p = 0.01; Reduced vision without impairment β = -2.30, p = 0.00). This study demonstrated that patients with craniopharyngioma show weaker neurocognitive performance in comparison to the normative population resulting from tumor, events leading to diagnosis, and early surgical intervention. Systematic investigation of neurocognitive performance before treatment with radiation therapy is essential to evaluating the potential risks and benefits of newer methods of radiation therapy including proton therapy.

Fournier-Goodnight|Ashley S|AS|
Ashford|Jason M|JM|
Merchant|Thomas E|TE|
Boop|Frederick A|FA|
Indelicato|Daniel J|DJ|
Wang|Lei|L|
Zhang|Hui|H|
Conklin|Heather M|HM|

Craniopharyngioma
Proton therapy
Learning and memory
Cognitive outcomes


Fate of Mycobacterium tuberculosis in peroxidase-loaded resting murine macrophages.

Abstract:
BACKGROUND
Myeloperoxidase (MPO), in the presence of hydrogen peroxide and a halide represent an efficient microbicidal mechanism of phagocytic cells. MPO is abundant in neutrophils which also respond to infection by producing large amounts of reactive oxygen species (ROS). MPO, ROS and halide constitute a very toxic antimicrobial system (called the Klebanoff system or KS). Resting mature macrophages do not contain granular MPO and thus are unable to kill pathogenic mycobacteria and some other microorganisms by this system.

EXPERIMENTAL
Under the hypothesis that transforming macrophages into peroxidase-positive (PO(+)) cells, these cells would be able to kill Mycobacterium tuberculosis, in this study, mature macrophages were loaded with exogenous peroxidase and were tested for their capacity to kill the Mycobacterium in the presence or in the absence of hydrogen peroxide.

RESULTS
It was found that PO-loaded macrophages eagerly ingest M. tuberculosis, but do not show a significant mycobactericidal activity on this microorganism despite that it is highly susceptible to the Klebanoff system in vitro. Failure of PO-loaded macrophages to kill M. tuberculosis may obey either to an inappropriate location of the exogenous PO in these cells or more likely, to the presence of efficient detoxifying mechanisms in the bacteria. On the contrary, MPO-loaded or unloaded macrophages efficiently killed Listeria monocytogenes.

CONCLUSION
The lack of granular MPO in mature macrophages, and the predilection of mycobacteria to infect these cells are two situations that favor the development of tuberculosis and related diseases, such as leprosy and Buruli ulcer.

Mendoza-Aguilar|Melby Dessiré|MD|
Arce-Paredes|Patricia|P|
Aquino-Vega|Mayda|M|
Rodríguez-Martínez|Sandra|S|
Rojas-Espinosa|Oscar|O|

Mycobacterium tuberculosis
Macrophages
Peroxidase


Characterisation of colonisation properties of vaginal lactobacilli from healthy Indian women: Implications for identification of potential probiotic candidates.

Abstract: The ability of probiotic bacteria to colonise the target site is considered of utmost importance and used for preliminary screening of potential probiotic candidates. Thirty-eight vaginal Lactobacillus strains isolated from healthy women and characterised by 16S RNA sequencing were assessed for colonisation characteristics including adherence to human vaginal epithelial cells, auto-aggregation and hydrophobicity. No significant difference in adherence (P = 0.384), auto-aggregation (P = 0.282) and hydrophobicity (P = 0.084) abilities between Lactobacillus species was observed, however, significant difference in colonisation characteristics between strains of the same species was noted (P < 0.001). We identified seven Lactobacillus strains that may serve as best candidates for vaginal probiotic development.

vaginal lactobacilli
probiotic
Adherence
auto-aggregation
cell surface hydrophobicity


Comparison of fractional wave equations for power law attenuation in ultrasound and elastography.

Abstract: A set of wave equations with fractional loss operators in time and space are analyzed. The fractional Szabo equation, the power law wave equation and the causal fractional Laplacian wave equation are all found to be low-frequency approximations of the fractional Kelvin-Voigt wave equation and the more general fractional Zener wave equation. The latter two equations are based on fractional constitutive equations, whereas the former wave equations have been derived from the desire to model power law attenuation in applications like medical ultrasound. This has consequences for use in modeling and simulation, especially for applications that do not satisfy the low-frequency approximation, such as shear wave elastography. In such applications, the wave equations based on constitutive equations are the viable ones.

Power law
Ultrasound
Elastography
Constitutive equations
Absorption
Fractional derivative
Lossy wave equation
Viscoelastic


The clinical characterization of the adult patient with depression aimed at personalization of management.

Abstract: Depression is widely acknowledged to be a heterogeneous entity, and the need to further characterize the individual patient who has received this diagnosis in order to personalize the management plan has been repeatedly emphasized. However, the research evidence that should guide this personalization is at present fragmentary, and the selection of treatment is usually based on the clinician's and/or the patient's preference and on safety issues, in a trial-and-error fashion, paying little attention to the particular features of the specific case. This may be one of the reasons why the majority of patients with a diagnosis of depression do not achieve remission with the first treatment they receive. The predominant pessimism about the actual feasibility of the personalization of treatment of depression in routine clinical practice has recently been tempered by some secondary analyses of databases from clinical trials, using approaches such as individual patient data meta-analysis and machine learning, which indicate that some variables may indeed contribute to the identification of patients who are likely to respond differently to various antidepressant drugs or to antidepressant medication vs. specific psychotherapies. The need to develop decision support tools guiding the personalization of treatment of depression has been recently reaffirmed, and the point made that these tools should be developed through large observational studies using a comprehensive battery of self-report and clinical measures. The present paper aims to describe systematically the salient domains that should be considered in this effort to personalize depression treatment. For each domain, the available research evidence is summarized, and the relevant assessment instruments are reviewed, with special attention to their suitability for use in routine clinical practice, also in view of their possible inclusion in the above-mentioned comprehensive battery of measures. The main unmet needs that research should address in this area are emphasized. Where the available evidence allows providing the clinician with specific advice that can already be used today to make the management of depression more personalized, this advice is highlighted. Indeed, some sections of the paper, such as those on neurocognition and on physical comorbidities, indicate that the modern management of depression is becoming increasingly complex, with several components other than simply the choice of an antidepressant and/or a psychotherapy, some of which can already be reliably personalized.

Maj|Mario|M|
Stein|Dan J|DJ|
Parker|Gordon|G|
Zimmerman|Mark|M|
Fava|Giovanni A|GA|
De Hert|Marc|M|
Demyttenaere|Koen|K|
McIntyre|Roger S|RS|
Widiger|Thomas|T|
Wittchen|Hans-Ulrich|HU|

Depression
personalization of treatment
neurocognition
physical comorbidities
severity
clinical staging
clinical subtypes
dysfunctional cognitive schemas
early environmental exposures
family history
functioning
personality traits
protective factors
psychiatric antecedents
psychiatric comorbidities
quality of life
recent environmental exposures
symptom profile


Moving to Beat Anxiety: Epidemiology and Therapeutic Issues with Physical Activity for Anxiety.

Abstract:
PURPOSE OF REVIEW
The purpose of this paper was to provide a comprehensive narrative review of the relationship between physical activity (PA) and anxiety and the rationale for including it as a treatment option for anxiety disorders. Several gaps in the literature are highlighted alongside recommendations for future research.

RECENT FINDINGS
PA in the general population has established efficacy in preventing and managing cardiovascular disease and improving wellbeing. Recent epidemiological data further suggests that people who are more active may be less likely to have anxiety disorders. In addition, evidence from systematic reviews of randomised control trials suggests that exercise training, a subset of PA, can reduce symptoms in anxiety and stress-related disorders, such as post-traumatic stress disorder, agoraphobia and panic disorder. Anxiety disorders are common, burdensome and costly to individuals and wider society. In addition to the profound negative impact on individuals' wellbeing and functioning, they are associated with worsened physical health, including a higher risk for cardiovascular diseases and premature mortality. Although pharmacotherapy and psychological interventions are helpful for many, these treatment approaches are not effective for everyone and are insufficient to address common physical health complications, such as the elevated risk of cardiovascular disease. Given the combined anxiolytic and physical health benefits of increased activity, PA presents a promising additional treatment option for people with anxiety disorders. However, there remain key gaps in the literature regarding the mechanisms underlying the effects of PA, optimal PA protocols, methods of improving adherence and the importance of physical fitness. These must be addressed for PA to be successfully implemented in mental health services.

Kandola|Aaron|A| Vancampfort|Davy|D| Herring|Matthew|M| Rebar|Amanda|A| Hallgren|Mats|M| Firth|Joseph|J| Stubbs|Brendon|B|

Cardiovascular disease
Exercise
Stress
Fitness
Mental health
Depression


Volume flow in arteriovenous fistulas using vector velocity ultrasound.

Abstract: Volume flow in arteriovenous fistulas for hemodialysis was measured using the angle-independent ultrasound technique Vector Flow Imaging and compared with flow measurements using the ultrasound dilution technique during dialysis. Using an UltraView 800 ultrasound scanner (BK Medical, Herlev, Denmark) with a linear transducer, 20 arteriovenous fistulas were scanned directly on the most superficial part of the fistula just before dialysis. Vector Flow Imaging volume flow was estimated with two different approaches, using the maximum and the average flow velocities detected in the fistula. Flow was estimated to be 242 mL/min and 404 mL/min lower than the ultrasound dilution technique estimate, depending on the approach. The standard deviations of the two Vector Flow Imaging approaches were 175.9 mL/min and 164.8 mL/min compared with a standard deviation of 136.9 mL/min using the ultrasound dilution technique. The study supports that Vector Flow Imaging is applicable for volume flow measurements.

Hansen|Peter Møller|PM|
Olesen|Jacob Bjerring|JB|
Pihl|Michael Johannes|MJ|
Lange|Theis|T|
Heerwagen|Søren|S|
Pedersen|Mads Møller|MM|
Rix|Marianne|M|
Lönn|Lars|L|
Jensen|Jørgen Arendt|JA|
Nielsen|Michael Bachmann|MB|

D000704:Analysis of Variance
D001132:Arm
D001166:Arteriovenous Shunt, Surgical
D001783:Blood Flow Velocity
D006801:Humans
D007676:Kidney Failure, Chronic
D006435:Renal Dialysis
D051437:Renal Insufficiency
D015203:Reproducibility of Results
D014463:Ultrasonography

Arteriovenous fistula
Ultrasound
Hemodialysis
Vector Flow Imaging
Ultrasound dilution technique
Flow velocity estimation
Volume flow estimation


Hydrothermal synthesis and characterization of Si and Sr co-substituted hydroxyapatite nanowires using strontium containing calcium silicate as precursors.

Abstract: In the absence of any organic surfactants and solvents, the silicon (Si) and strontium (Sr) co-substituted hydroxyapatite [Ca10(PO4)6(OH)2, Si/Sr-HAp] nanowires were synthesized via hydrothermal treatment of the Sr-containing calcium silicate (Sr-CS) powders as the precursors in trisodium phosphate (Na3PO4) aqueous solution. The morphology, phase, chemical compositions, lattice constants and the degradability of the products were characterized. The Si/Sr-HAp nanowires with diameter of about 60nm and up to 2μm in length were obtained after hydrothermal treatment of the Sr-CS precursors. The Sr and Si substitution amount of the HAp nanowires could be well regulated by facile tailoring the Sr substitution level of the precursors and the reaction ratio of the precursor/solution, respectively. The SiO4 tetrahedra and Sr(2+) ions occupied the crystal sites of the HAp, and the lattice constants increased apparently with the increase of the substitution amount. EDS mapping also suggested the uniform distribution of Si and Sr in the synthetic nanowires. Moreover, the Si/Sr-substitution apparently improved the degradability of the HAp materials. Our study suggested that the precursor transformation method provided a facile approach to synthesize the Si/Sr co-substituted HAp nanowires with controllable substitution amount, and the synthetic Si/Sr-HAp nanowires might be used as bioactive materials for hard tissue regeneration applications.

Zhang|Na|N| Zhai|Dong|D| Chen|Lei|L| Zou|Zhaoyong|Z| Lin|Kaili|K| Chang|Jiang|J|

Co-substitution
Hydroxyapatite nanowires
Strontium
Silicon
Lattice constants
Precursor transformation


Facile synthesis of a core-shell structured magnetic covalent organic framework for enrichment of organophosphorus pesticides in fruits.

Abstract: A facile strategy was developed for the fabrication of a magnetic covalent organic framework (COF) via grafting of the monomers, 2,5-dihydroxyterephthalaldehyde (Dt) and 1,3,5-tris(4-aminophenyl) benzene (Tb) onto surface-modified Fe3O4 nanoparticles. The magnetic COF, named as magnetic COF-DtTb, was readily fabricated without high temperature or harsh reaction conditions. The synthesized magnetic COF-DtTb nanoparticles were fully characterized, presenting a regular core-shell spherical structure, large specific surface area, superparamagnetism, and good thermal stability. Their potential as an enrichment adsorbent was investigated to establish an efficient magnetic solid-phase extraction method for the determination of organophosphorus pesticide residues in fruits. Systematic method validation revealed good linearity in the concentration range of 1-200 μg L-1 (correlation coefficient >0.9957). The method limits of detection were in the range of 0.002-0.063 μg kg-1, the method limit of quantification was 1.00 μg kg-1 and recoveries ranged from 72.8% to 111% with RSDs lower than 12.3%. The results indicated that magnetic COF-DtTb possesses superior trace enrichment properties for organophosphorus pesticides in fruits.

Lin|Xiangping|X| Wang|Xinquan|X| Wang|Jiao|J| Yuan|Yuwei|Y| Di|Shanshan|S| Wang|Zhiwei|Z| Xu|Hao|H| Zhao|Huiyu|H| Qi|Peipei|P| Ding|Wei|W|

D021241:Spectrometry, Mass, Electrospray Ionization

Magnetic covalent organic framework
Organophosphorus pesticides
Fruits
Magnetic solid-phase extraction


In vitro formation of Maillard reaction products during simulated digestion of meal-resembling systems.

Abstract: The aim of the present research was to study the formation of Maillard reaction products (MRPs) during digestive process of meal-resembling systems. An average meal (protein, starch and oil) and sugar-containing meals (protein and glucose or fructose or high fructose corn syrup (HCFS)) were tested. Intestinal simple amino acid systems were also analyzed to gain insight into their contribution to the Maillard reaction (MR). Decrease of lysine (11.7-34%), arginine (24-35%) and other amino acids occurred after digestion of the meals. Fructosamine (42.6±4.7 and 332.9±10.4μg/ml) and fluorescent adducts (22,270±119.6 and 9283±188.3 RFU) were detected in digests of those meals containing HCFS and starch, respectively. Carboxymethyllysine (CML) (5.03±1.09μg/ml) and MGO-derivative AGEs (12.2±1.5μg/ml) were found in the meals composed of fructose and only MGO-derivative AGEs (12.2±1.6μg/ml) in presence of glucose. Physiological intestinal concentrations (43mM) of sugars in simplified systems composed by single amino acids caused formation of MRPs under digestive conditions. Arginine and fructose (314mM) showed formation of fructosamine and different AGEs. Fructose (43mM) gave rise to CML by interaction with lysine, which was observed within 1h of incubation at intestinal conditions. These conditions are possible in the intestine during fructose malabsorption. The results suggest the importance of using meal systems for better understanding of complex chemical events taking place during digestion such as MR. This is the first study proposing the formation of non-fluorescent AGEs associated to the pathogenesis of diabetes during digestion of sugar containing and average meals. This formation may be possible in conditions where sugar absorption is delayed such as fructose malabsorption or intake of a fatty meal. The occurrence of the MR during the digestion process may reduce the bioavailability of essential amino acids and increase the production of MRPs causing health disorders.

Martinez-Saez|Nuria|N|
Fernandez-Gomez|Beatriz|B|
Cai|Weijing|W|
Uribarri|Jaime|J|
Del Castillo|María Dolores|MD|

Digestion
MRPs
Average meal
Sugar-containing meals
AGEs
Malabsorption
Amino acids bioavailability
Delayed sugar absorption


Right Heart Pulmonary Circulation Unit Involvement in Left-Sided Heart Failure: Diagnostic, Prognostic, and Therapeutic Implications.

Abstract: Although long neglected, the right heart (RH) is now widely accepted as a pivotal player in heart failure (HF) either with reduced or preserved ejection fraction. The chronic overload of the pulmonary microcirculation results in an initial phase characterized by right ventricular (RV) hypertrophy, right atrial dilation, and diastolic dysfunction. This progresses to overt RH failure when RV dilation and systolic dysfunction lead to RV-pulmonary arterial (RV-PA) uncoupling with low RV output. In the context of its established relevance to progression of HF, clinicians should consider assessment of the RH with information from clinical assessment, biomarkers, and imaging. Notably, no single parameter can predict prognosis alone in HF. Assessments simultaneously should encompass RV systolic function, pulmonary pressures, an estimation of RV-PA coupling, and RH morphologic features. Despite a large volume of evidence indicating the relevance of RH function to the clinical syndrome of HF, evidence-based management strategies are lacking. Targeting RH dysfunction in HF should be an objective of future investigations, being an unmet need in the current management of HF.

Marra|Alberto M|AM|
Sherman|Alexander E|AE|
Salzano|Andrea|A|
Guazzi|Marco|M|
Saggar|Rajan|R|
Squire|Ian B|IB|
Cittadini|Antonio|A|
Channick|Richard|R|
Bossone|Eduardo|E|

left heart failure
pulmonary hypertension
right heart failure


Applying a nonlinear, pitch-catch, ultrasonic technique for the detection of kissing bonds in friction stir welds.

Abstract: Friction stir welding (FSW) is a promising technology for the joining of aluminum alloys and other metallic admixtures that are hard to weld by conventional fusion welding. Although FSW generally provides better fatigue properties than traditional fusion welding methods, fatigue properties are still significantly lower than for the base material. Apart from voids, kissing bonds for instance, in the form of closed cracks propagating along the interface of the stirred and heat affected zone, are inherent features of the weld and can be considered as one of the main causes of a reduced fatigue life of FSW in comparison to the base material. The main problem with kissing bond defects in FSW, is that they currently are very difficult to detect using existing NDT methods. Besides, in most cases, the defects are not directly accessible from the exposed surface. Therefore, new techniques capable of detecting small kissing bond flaws need to be introduced. In the present paper, a novel and practical approach is introduced based on a nonlinear, single-sided, ultrasonic technique. The proposed inspection technique uses two single element transducers, with the first transducer transmitting an ultrasonic signal that focuses the ultrasonic waves at the bottom side of the sample where cracks are most likely to occur. The large amount of energy at the focus activates the kissing bond, resulting in the generation of nonlinear features in the wave propagation. These nonlinear features are then captured by the second transducer operating in pitch-catch mode, and are analyzed, using pulse inversion, to reveal the presence of a defect. The performance of the proposed nonlinear, pitch-catch technique, is first illustrated using a numerical study of an aluminum sample containing simple, vertically oriented, incipient cracks. Later, the proposed technique is also applied experimentally on a real-life friction stir welded butt joint containing a kissing bond flaw.

Delrue|Steven|S|
Tabatabaeipour|Morteza|M|
Hettler|Jan|J|
Van Den Abeele|Koen|K|

Nonlinearity
Kissing bonds
Friction stir welding
Comsol
Non-destructive testing


A quantitative method for the selective 5-HT2A agonist 25CN-NBOH in rat plasma and brain.

Abstract: In recent years, agonists of the 5-HT2A receptor have gained increasing attention for their potential therapeutic use to treat psychological disorders such as anxiety and depression. Here, we report the development and validation of an LC-MSMS based analytical method for the quantification of the novel selective 5-HT2A agonist 25CN-NBOH in rat plasma and brain. As simple and efficient sample clean-up we applied the Phree Phospholipid Removal approach from Phenomenex, which is particularly novel for brain samples. In order to investigate the metabolic stability of 25CN-NBOH in vitro biotransformation studies with recombinant enzymes and human liver microsomes were conducted. Several biotransformation products and pathways could be identified. Based on the in vitro study one of the putative metabolites (2C-CN) was included in the analytical method development. To test the methods applicability 25CN-NBOH was quantified in plasma and brain samples from a pharmacokinetic in vivo study with Wildtype Long Evans rats. Both the in vitro metabolism data as well as the in vivo PK data suggest that 25CN-NBOH is susceptible to metabolism, but is degraded slower and is more stable compared to other NBOMe's investigated to date. The developed analytical method might serve as basis to include further 25CN-NBOH metabolites. It is expected to facilitate further preclinical and clinical investigations of 25CN-NBOH in biological matrices.

Breusova|Kateryna|K|
Ernstsen|Kristian Goldeman|KG|
Palner|Mikael|M|
Linnet|Kristian|K|
Kristensen|Jesper Langgaard|JL|
Kretschmann|Andreas Christopher|AC|

D058826:Serotonin 5-HT2 Receptor Agonists

25CN-NBOH
LC-MSMS
Phospholipid removal
Metabolism
Pharmacokinetics
5-HT(2A) agonist


Long term soil carbon sequestration potential of smallholder croplands in southern Ethiopia with DAYCENT model.

Abstract: Considering the importance of soil organic carbon (SOC) and the scarcity of data on how soil management influences its storage in the region, this study assessed the long-term impact of different soil management systems on SOC in southern Ethiopia using the DAYCENT model. The conservation management systems considered were minimum tillage, crop residue (CR) retention, fertilization and their combinations. We parameterized the model with data from studies in the literature. We then modeled conventional cropping system for smallholding farms over a 30-year period (1991-2020) as the business as usual scenario (BAU). Then we assessed the impact of alternative conservation management scenarios compared with the BAU scenario. Our results indicated that the conservation management scenarios increased SOC at 0-20 cm depth in the range 0.34-9.71 Mg C ha-1 over 30 years when compared to BAU practices. The individual effect of fertilization, CR retention or minimum tillage management practices on SOC stock were lower than the response of the combined conservation management practices. The combined 50%-75% CR retention, no-tillage (NT), and 32 kg N ha-1 fertilization provided the highest SOC sequestration. These combinations, increased SOC in the range 8.10-9.71 Mg C ha-1 over 30 years equivalent to rates of 0.27-0.32 Mg C ha-1 yr-1. While long-term empirical data from field experiments are lacking, model results suggest that the combined 50-75% CR retention, NT, and increased N fertilization have a potential to increase SOC sequestration in resource-limited smallholding croplands. The results may be useful for researchers, policy maker and other stakeholders.

Smallholding croplands
Daycent model
Conservation management system
Soil organic C sequestration


Expansion of syndromic vaccine preventable disease surveillance to include bacterial meningitis and Japanese encephalitis: evaluation of adapting polio and measles laboratory networks in Bangladesh, China and India, 2007-2008.

Abstract:
BACKGROUND
Surveillance for acute flaccid paralysis with laboratory confirmation has been a key strategy in the global polio eradication initiative, and the laboratory platform established for polio testing has been expanded in many countries to include surveillance for cases of febrile rash illness to identify measles and rubella cases. Vaccine-preventable disease surveillance is essential to detect outbreaks, define disease burden, guide vaccination strategies and assess immunization impact. Vaccines now exist to prevent Japanese encephalitis (JE) and some etiologies of bacterial meningitis.

METHODS
We evaluated the feasibility of expanding polio-measles surveillance and laboratory networks to detect bacterial meningitis and JE, using surveillance for acute meningitis-encephalitis syndrome in Bangladesh and China and acute encephalitis syndrome in India. We developed nine syndromic surveillance performance indicators based on international surveillance guidelines and calculated scores using supervisory visit reports, annual reports, and case-based surveillance data.

RESULTS
Scores, variable by country and targeted disease, were highest for the presence of national guidelines, sustainability, training, availability of JE laboratory resources, and effectiveness of using polio-measles networks for JE surveillance. Scores for effectiveness of building on polio-measles networks for bacterial meningitis surveillance and specimen referral were the lowest, because of differences in specimens and techniques.

CONCLUSIONS
Polio-measles surveillance and laboratory networks provided useful infrastructure for establishing syndromic surveillance and building capacity for JE diagnosis, but were less applicable for bacterial meningitis. Laboratory-supported surveillance for vaccine-preventable bacterial diseases will require substantial technical and financial support to enhance local diagnostic capacity.

Cavallaro|Kathleen F|KF|
Sandhu|Hardeep S|HS|
Hyde|Terri B|TB|
Johnson|Barbara W|BW|
Fischer|Marc|M|
Mayer|Leonard W|LW|
Clark|Thomas A|TA|
Pallansch|Mark A|MA|
Yin|Zundong|Z|
Zuo|Shuyan|S|
Hadler|Stephen C|SC|
Diorditsa|Serguey|S|
Hasan|A S M Mainul|AS|
Bose|Anindya S|AS|
Dietz|Vance|V|
|||

Vaccine preventable diseases
Surveillance
Meningitis
Japanese encephalitis
VPD


Mean platelet volume in children with Reye-like syndrome.

Abstract: Reye-like syndrome (RLS) is considered to be a systemic disorder in which the cytokine storm plays a major role. Mean platelet volume (MPV), which is commonly used as a measure of platelet size, indicates the rate of platelet production and platelet activation. We aimed to study MPV in children with RLS. The study population consisted of 30 children with RLS and 30 healthy control subjects. White blood cell (WBC) count, aspartate transaminase (AST) and alanine transaminase (ALT) values were significantly higher and MPV values were significantly lower in patients with RLS at an early stage of illness when compared to controls. Erythrocyte sedimentation rate (ESR), C-reactive protein, AST and ALT values were significantly decreased in patients with RLS after the treatment when compared to baseline whereas MPV values were increased. MPV values were negatively correlated with ESR and WBC. In conclusion, at an early stage of RLS MPV values were lower when compared to controls.

Sert|Ahmet|A|
Kilicaslan|Cengizhan|C|
Solak|Ece Selma|ES|
Arslan|Sukru|S|

Mean platelet volume
platelets
Reye-like syndrome


How changing root system architecture can help tackle a reduction in soil phosphate (P) levels for better plant P acquisition.

Abstract: The readily available global rock phosphate (P) reserves may run out within the next 50-130 years, causing soils to have a reduced P concentration which will affect plant P uptake. Using a combination of mathematical modelling and experimental data, we investigated potential plant-based options for optimizing crop P uptake in reduced soil P environments. By varying the P concentration within a well-mixed agricultural soil, for high and low P (35.5-12.5 mg L(-1) respectively using Olsen's P index), we investigated branching distributions within a wheat root system that maximize P uptake. Changing the root branching distribution from linear (evenly spaced branches) to strongly exponential (a greater number of branches at the top of the soil) improves P uptake by 142% for low-P soils when root mass is kept constant between simulations. This causes the roots to emerge earlier and mimics topsoil foraging. Manipulating root branching patterns, to maximize P uptake, is not enough on its own to overcome the drop in soil P from high to low P. Further mechanisms have to be considered to fully understand the impact of P reduction on plant development.

Heppell|J|J|
Talboys|P|P|
Payvandi|S|S|
Zygalakis|K C|KC|
Fliege|J|J|
Withers|P J A|PJ|
Jones|D L|DL|
Roose|T|T|

modelling
Triticum aestivum
plant nutrient uptake
rhizosphere
root architecture


Sestamibi scan in renal parathyroidectomy: a worthwhile preoperative exam?

Abstract:
INTRODUCTION
Surgical treatment of hyperparathyroidism related to chronic kidney disease is a real challenge for Brazilian public health care. High cost medications and long waiting lines to perform preoperative exams, especially technetium Tc 99m Sestamibi (MIBI) are some of the reasons. Despite the reality that the aid of localization exams are questionable in this scenario, doctors are too apprehensive in performing surgery without it.

OBJECTIVE
The study aimed at evaluating the efficacy of surgery for renal hyperparathyroidism without preoperative MIBI.

METHODS
A total of 114 patients were surgically treated. Total parathyroidectomy with autotransplantation and subtotal parathyroidectomy were carried out without preoperative MIBI.

RESULTS AND CONCLUSION
Among the 114 patients undergoing surgery, 37 had secondary hyperparathyroidism in dialysis replacement, and 77 patients had post-renal transplant persistent disease. We were successful in 107 cases with only 7 failures (93.8% of success rate). Among these failures, only one parathyroid gland was not found in 4 cases, 2 parathyroid glands were not found in 2 cases and in 1 patient the 4 glands were found but this patient remained hypercalcemic and a postoperative diagnosis of supernumerary parathyroid gland was made. Surgery for treatment of renal hyperparathyroidism proved to be an effective (93.8%) and reproductible procedure, even without MIBI.

Machado|Hanna Karla Andrade Guapyassu|HKAG|

Chronic kidney disease-mineral and bone disorder

Doença renal crônica - distúrbio mineral e ósseo


Offspring genes indirectly influence sibling and maternal behavioural strategies over resource share.

Abstract: Family members show behavioural strategies predicted to maximize individual fitness. These behaviours depend directly on genes expressed in focal individuals but also indirectly on genes expressed in other family members. However, how sibling and parental behavioural strategies are modified by genes expressed in family members, and to what degree, remains unclear. To answer this question, we have used a split litter design in an experimental population of genetically variable mouse families, and identified loci that indirectly affected sibling and maternal behaviour simultaneously. These loci map to genomic regions that also show a direct effect on offspring behaviour. Directly and indirectly affected traits were significantly correlated at the phenotypic level, illustrating how indirect effects are caused. Genetic variants in offspring that influence solicitation also impacted their siblings' and maternal behaviour. However, in contrast to predictions from sibling competition, unrelated litter mates benefited from increased solicitation. Overall, such indirect genetic effects explained a large proportion of variation seen in behaviours, with candidate genes involved in metabolism to neuronal development. These results reveal that we need to view behavioural strategies as the result of conjoint selection on genetic variation in all interacting family members.

indirect genetic effects
family conflicts
parent–offspring conflict
systems genetics


Effect of chronic consumption of pistachios (Pistacia vera L.) on glucose metabolism in pre-diabetics and type 2 diabetics: A systematic review.

Abstract: Pistachio is a nut with high polyunsaturated fatty acids (PUFA), monounsaturated fatty acids (MUFA), polyphenols and carotenoids content, and the synergism between these compounds appears to affect glucose metabolism. In this systematic review we analyzed studies in which the effect of chronic consumption of pistachio on markers of glucose metabolism was evaluated in pre-diabetic and type 2 diabetics. We used the PubMed, Scopus, Cochrane and Lilacs databases. The research terms used were pistachio, pre-diabetes, type 2 diabetes mellitus, insulin resistance, blood glucose, hyperglycemia and glycated hemoglobin (HbA1c). Four articles were selected, of which three tested the intake of 50 to 57 g of pistachio/day and one 20% of the daily caloric intake, for a period of 1 to 4 months. Studies reported a decrease in fasting blood glucose, insulinemia, HOMA-IR, and fructosamine, but no change in HbA1c. Lower concentrations of miR-192 and miR-375 were also found, which correlated positively with HOMA-IR. The synergism between PUFA, MUFA, polyphenols and carotenoids present in pistachios can modulate specific miRNA, increasing insulin sensitivity through the PI3K-AKT signaling pathway. This modulation can be used as a tool to monitor the response to interventions, favoring the prevention and treatment of complications related to diabetes.

Pistachio
Polyphenols
Carotenoids
Insulin resistance
MicroRNAs
Unsaturated fatty acids


Transition from mesenchymal to bleb-based motility is predominantly exhibited by CD133-positive subpopulation of fibrosarcoma cells.

Abstract:
BACKGROUND INFORMATION
Metastatic disease is caused by the ability of cancer cells to reach distant organs and form secondary lesions at new locations. Dissemination of cancer cells depends on their migration plasticity - an ability to switch between motility modes driven by distinct molecular machineries. One of such switches is mesenchymal-to-amoeboid transition. Although mesenchymal migration of individual cells requires Arp2/3-dependent actin polymerisation, amoeboid migration is characterised by a high level of actomyosin contractility and often involves the formation of membrane blebs. The acquisition of amoeboid motility by mesenchymal cells is often associated with enhanced metastasis.

RESULTS
We studied the ability of mesenchymal HT1080 fibrosarcoma cells to switch to amoeboid motility. We induced the transition from lamellipodium-rich to blebbing phenotype either by down-regulating the Arp2/3 complex, pharmacologically or by RNAi, or by decreasing substrate adhesiveness. Each of these treatments induced blebbing in a subset of fibrosarcoma cells, but not in normal subcutaneous fibroblasts. A significant fraction of HT1080 cells that switched to blebbing behaviour exhibited stem cell-like features, such as expression of the stem cell marker CD133, an increased efflux of Hoechst-33342 and positive staining for Oct4, Sox2 and Nanog. Furthermore, the isolated CD133+ cells demonstrated an increased ability to switch to bleb-rich amoeboid phenotype both under inhibitor's treatment and in 3D collagen gels.

CONCLUSIONS
Together, our data show a significant correlation between the increased ability of cells to switch between migration modes and their stem-like features, suggesting that migration plasticity is an additional property of stem-like population of fibrosarcoma cells. This combination of features could facilitate both dissemination of these cells to distant locations, and their establishment self-renewal in a new microenvironment, as required for metastasis formation.

SIGNIFICANCE
These data suggest that migration plasticity is a new feature of cancer stem-like cells that can significantly facilitate their dissemination to a secondary location by allowing them to adapt quickly to challenging microenvironments. Moreover, it complements their resistance to apoptosis and self-renewal potential, thus enabling them not only to disseminate efficiently, but also to survive and colonise new niches.

D051376:Actin-Related Protein 2-3 Complex

blebs
Arp2/3 complex
actin cytoskeleton
cell motility
lamellipodia


Possible roles of basic helix-loop-helix transcription factors in adaptation to drought.

Abstract: Water deficiency decreases plant growth and productivity. Several mechanisms are activated in response to dehydration that allows plants to cope with stress, including factors controlling stomatal aperture and ramified root system development. In addition, ABA metabolism is also implicated in the regulation of drought responses. The basic helix-loop-helix (bHLH) proteins, a large family of conserved transcription factors that regulates many cellular processes in eukaryotic organisms, are also involved in several responses that are important for plants to cope with drought stress. This review discusses distinct mechanisms related to drought-adaptive responses, especially the possible involvement of the bHLH transcription factors such as MUTE, implicated in stomatal development; RD22, [corrected] an ABA-responsive gene; EGL3 and GL3, involved in thichome and root hair development; and SPT, which play roles in repressing leaf expansion. Transcription factors are potential targets for new strategies to increase the tolerance of cultivars to drought stress. Recognition of gene regulatory networks in crops is challenging, and the manipulation of bHLH genes as well as components that mediate bHLH transcription factor responses in different pathways could be essential to achieve abiotic stress tolerance in plants through genetic manipulation.

Castilhos|Graciela|G|
Lazzarotto|Fernanda|F|
Spagnolo-Fonini|Leila|L|
Bodanese-Zanettini|Maria Helena|MH|
Margis-Pinheiro|Márcia|M|

D051792:Basic Helix-Loop-Helix Transcription Factors

Basic helix-loop-helix
Transcription factor
Drought stress
Root hair
Stomata
Trichome


Association between asymptomatic intracranial arterial stenosis and insulin resistance or diabetes mellitus: a cross-sectional study in rural Shandong, China.

Abstract:
INTRODUCTION
Recent studies have shown that insulin resistance (IR) is correlated to atherosclerosis development. However, few studies have investigated the association between IR and asymptomatic intracranial arterial stenosis (aICAS).

RESEARCH DESIGN AND METHODS
This cross-sectional study enrolled 2007 rural residents in China who were aged ≥40 years without a clinical history of stroke and transient ischaemic attack. We used transcranial Doppler ultrasonography in combination with magnetic resonance angiography to diagnose aICAS (stenosis ≥50%). IR was defined as a homeostasis model assessment of insulin resistance ≥3.0 based on the 75th percentile for all the participants. Multivariate logistic regression models were employed to assess the relationship of diabetic parameters with aICAS in all participants, as well as with aICAS in non-diabetic participants, and further stratified by sex.

RESULTS
After adjusting for age, gender, smoking habit, drinking habit, low-density lipoprotein cholesterol, raised blood pressure, triglycerides, high-density lipoprotein cholesterol and waist circumference, diabetes mellitus (DM) (OR=2.09, 95% CI 1.31 to 3.32), fasting plasma glucose (FPG) (OR=1.34, 95% CI 1.14 to 1.57), and IR (OR=1.75, 95% CI 1.11 to 2.75) were associated with aICAS in the total study population; however, these relationships remained significant only in men after the analyses were stratified by sex (DM: OR=3.40, 95% CI 1.62 to 7.13; FPG: OR=1.64, 95% CI 1.26 to 2.13; IR: OR=3.04, 95% CI 1.44 to 6.42). When further excluding the diabetic participants from the total study population, positive associations between IR and aICAS were similarly observed only in men (OR=4.65, 95% CI 1.69 to 12.82).

CONCLUSIONS
IR might predict the prevalence of aICAS independently of major cardiovascular risk factors and metabolic syndrome components among men living in rural China.

Wang|Qiao|Q| Zhao|Yuanyuan|Y| Wang|Xiang|X| Ji|Xiaokang|X| Sang|Shaowei|S| Shao|Sai|S| Ma|Xiaotong|X| Wang|Guangbin|G| Lv|Ming|M| Xue|Fuzhong|F| Du|Yifeng|Y| Sun|Qinjian|Q|0000-0002-9323-9154

insulin resistance
atherosclerosis
metabolic syndrome
asymptomatic diseases


The mRNA expression of amino acid transporters, aminopeptidase N, and the di- and tri-peptide transporter PepT1 in the embryo of the domesticated chicken (Gallus gallus) shows developmental regulation.

Abstract: The mRNA expression profile for 10 amino acid transporters, the di-and tri- peptide transporter (PepT1), and aminopeptidase N (APN) during chick embryogenesis was determined. Fertilized eggs were sampled at d 9, 11, 15, 17, 19, and 20 of incubation. Three to 4 embryos were sampled at each time period. At d 9 and 11, the entire intestine was collected due to its undifferentiated appearance. The ceca, duodenum, midgut, and liver were sampled at d 15, 17, 19, and 20. Gene expression was measured using absolute quantitation quantitative reverse-transcription PCR. In the liver, all genes except for PepT1 were expressed at most time points. At d 9, only the expression of Na⁺-independent cationic amino acid transporter 1, Na⁺-independent cationic amino acid transporter 2, and excitatory amino acid transporter 3 was detectable in the intestine, but by d 11, all genes associated with transporters of the basolateral surface were expressed, and at higher levels than genes associated with brush border transporters. By d 15, all of the genes tested were expressed in the duodenum, midgut, and ceca at high levels that remained relatively constant until d 20. Statistical analysis shows that at d 15, 17, 19, and 20 there is a significant interaction between the 2 main effects (days of incubation and region of the gut); therefore, it is likely that gene expression in different regions of the gut is dependent on the age of the embryo. At d 9 and 11, the gut may not function in amino acid uptake from the lumen and possibly relies on other structures such as the yolk sac. As the gut matures and protein becomes available in the lumen, amino acid transporters become highly expressed in all parts of the intestine. The data suggest that by d 15 of embryo development the gut may be capable of amino acid absorption.

Miska|Katarzyna B|KB|
Fetterer|Raymond H|RH|
Wong|Eric A|EA|

D018507:Gene Expression Regulation, Developmental

D060888:Real-Time Polymerase Chain Reaction

amino acid transporter
embryo
chicken
gene expression


Initiation Patterns of Statins in the 2 Years After Release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Cholesterol Management Guideline in a Large US Health Plan.

Abstract:
BACKGROUND
The purpose of this study was to characterize changes in statin utilization patterns in patients newly initiated on therapy in the 2 years following the release of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol management guideline in a large US health plan population.

METHODS AND RESULTS
This retrospective, observational study used administrative medical and pharmacy claims data to identify patients newly initiated on statin therapy over 4 quarters prior to and 8 quarters following the release of the guideline (average N/quarter=3596). Patients were divided into the 4 statin benefit groups (SBGs) based on risk factors and laboratory lipid levels as defined in the guideline: SBG1 (with atherosclerotic cardiovascular disease [ASCVD]; N=1046/quarter), SBG2 (without ASCVD, with low-density lipoprotein cholesterol ≥190 mg/dL; N=454/quarter), SBG3 (without ASCVD, aged 40-75 years, with diabetes mellitus, low-density lipoprotein cholesterol 70-189 mg/dL; N=1391/quarter), SBG4 (no ASCVD or diabetes mellitus, age 40-75 years, low-density lipoprotein cholesterol 70-189 mg/dL, estimated 10-year ASCVD risk of ≥7.5%; N=705/quarter). Demographic variables, statin utilization patterns, lipid levels, and comorbidities were analyzed for pre- and postguideline periods. Postguideline, gradually increased high-intensity statin initiation occurred in SBG1, SBG2, and in SBG3 patients with 10-year ASCVD risk ≥7.5%. Moderate- to high-intensity statin initiation gradually increased among SBG4 patients. Recommended-intensity statin choice changed to a greater degree among patients treated by specialty care physicians. Regarding sex, target-intensity statin initiation was lower in women in all groups before and after guideline release.

CONCLUSIONS
Prescriber implementation of the guideline recommendations has gradually increased, with the most marked change in the increased initiation of high-intensity statins in patients with ASCVD and in those treated by a specialist.

Olufade|Temitope|T|
Zhou|Siting|S|
Anzalone|Deborah|D|
Kern|David M|DM|
Tunceli|Ozgur|O|
Cziraky|Mark J|MJ|
Willey|Vincent J|VJ|


Effect of Therapeutic Drug Monitoring and Cytochrome P450 2C19 Genotyping on Clinical Outcomes of Voriconazole: A Systematic Review.

Abstract:
OBJECTIVES
To examine current knowledge on the clinical utility of therapeutic drug monitoring (TDM) in voriconazole therapy, the impact of CYP2C19 genotype on voriconazole plasma concentrations, and the role of CYP2C19 genotyping in voriconazole therapy.

DATA SOURCES
Three literature searches were conducted for original reports on (1) TDM and voriconazole outcomes and (2) voriconazole and CYP2C19 polymorphisms. Searches were conducted through EMBASE, MEDLINE/PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception to June 2020.

STUDY SELECTION AND DATA EXTRACTION
Randomized controlled trials, cohort studies, and case series with ≥10 patients were included. Only full-text references in English were eligible.

DATA SYNTHESIS
A total of 63 studies were reviewed. TDM was recommended because of established concentration and efficacy/toxicity relationships. Voriconazole trough concentrations ≥1.0 mg/L were associated with treatment success; supratherapeutic concentrations were associated with increased neurotoxicity; and hepatotoxicity associations were more prevalent in Asian populations. CYP2C19 polymorphisms significantly affect voriconazole metabolism, but no relationship with efficacy/safety were found. Genotype-guided dosing with TDM was reported to increase chances of achieving therapeutic range.

RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Genotype-guided dosing with TDM is a potential solution to optimizing voriconazole efficacy while avoiding treatment failures and common toxicities.

CONCLUSIONS
Voriconazole plasma concentrations and TDM are treatment outcome predictors, but research is needed to form a consensus target therapeutic range and dosage adjustment guidelines based on plasma concentrations. CYP2C19 polymorphisms are a predictor of voriconazole concentrations and metabolism, but clinical implications are not established. Large-scale, high-methodological-quality trials are required to investigate the role for prospective genotyping and establish CYP2C19-guided voriconazole dosing recommendations.

D064420:Drug-Related Side Effects and Adverse Reactions

therapeutic drug monitoring
voriconazole
systematic review
CYP2C19
genotype-guided dosing
pharmacokinetics


Patients With Vasculitides Admitted to the Intensive Care Unit: Implications From a Single-Center Retrospective Study.

Abstract:
BACKGROUND
Vasculitides are a group of disorders characterized by inflammation of vessels. Vasculitides may have life-threatening complications with significant morbidity and mortality; however, information regarding the outcome and prognosis of patients with vasculitides requiring intensive care unit (ICU) is scarce.

METHODS
Data of patients with vasculitides admitted to the ICU of the Sheba Medical Center between the years 2000 and 2014 were retrieved retrospectively. Continuous variables were computed as mean (standard deviation), whereas categorical variables were recorded as percentages. In order to investigate the impact of clinical variables on mortality, Student t test and χ2 analyses were performed.

RESULTS
Twenty-five patients with vasculitides were admitted to the ICU during the study period with mean age of 52 ± 14 years and sex ratio of male/female: 12/13. The mortality rate among these patients was 48%. Leading causes for ICU admission were infection (64%), disease exacerbation (34%), and hemorrhage (16%), while respiratory or cardiovascular involvement accounted for the majority of mortality during admission. An elevated Sequential Organ Failure Assessment (SOFA) score was significantly associated with mortality (P = .041).

CONCLUSION
Our study confirms the high mortality rate among patients with vasculitides who require ICU care as well as the roles of infection and disease flare-up as causes for admission. An elevated SOFA score was found to be predictive of mortality.

intensive care unit
SOFA
ANCA
APACHE
rituximab
vasculitis


THz pulse doubler at FLASH: double pulses for pump-probe experiments at X-ray FELs.

Abstract: FLASH, the X-ray free-electron laser in Hamburg, Germany, employs a narrowband high-field accelerator THz source for unique THz pump X-ray probe experiments. However, the large difference in optical paths of the THz and X-ray beamlines prevents utilization of the machine's full potential (e.g. extreme pulse energies in the soft X-ray range). To solve this issue, lasing of double electron bunches, separated by 28 periods of the driving radiofrequency (at 1.3 GHz), timed for the temporal overlap of THz and X-ray pulses at the experimental station has been employed. In order to optimize conditions for a typical THz pump X-ray probe experiment, X-ray lasing of the first bunch to one-sixth of that of the second has been suppressed. Finally, synchronization of THz radiation pulses was measured to be ∼20 fs (r.m.s.), and a solution for monitoring the arrival time for achieving higher temporal resolution is presented.

FLASH
X-rays
free-electron laser
double electron bunches
THz beamline
pump–probe experiments


Immigrant Status and Sexual Orientation Disclosure: Implications for HIV/STD Prevention Among Men Who Have Sex with Men in Seattle, Washington.

Abstract: Men who have sex with men (MSM) are disproportionately affected by HIV and may avoid disclosing their sexual preferences to others. With heightened attention on immigrant status in the United States, foreign-born MSM may be particularly concerned about disclosing their sexual orientation. We sought to examine how immigrant status is associated with sexual orientation disclosure among MSM and to assess the impact of disclosure on HIV/STD prevention outcomes stratified by nativity. We analyzed data from the 2014 and 2017 Seattle-area surveys of MSM from the National HIV Behavioral Surveillance (NHBS) system. Foreign-born MSM were less likely than U.S.-born MSM to have disclosed their sexuality to friends who are not gay, lesbian, or bisexual (85.0% vs. 95.5%; p < .001) or to family members (80.5% vs. 91.3%; p < .001). Further, disclosure to one's health care provider significantly increased the likelihood of having tested for HIV in the past 12 months among foreign-born and U.S.-born MSM. Findings highlight the need to better understand the risks and benefits of disclosure among foreign-born MSM. Future research may explore how responses and reactions to disclosure among foreign-born MSM shape pathways to HIV risk and prevention.

Lee|Jane J|JJ|
Katz|David A|DA|
Glick|Sara N|SN|
Moreno|Courtney|C|
Kerani|Roxanne P|RP|

Immigrant status
Sexual orientation disclosure
HIV/STD prevention
MSM


Using protection motivation theory to explain the intention to initiate human papillomavirus vaccination among men who have sex with men in China.

Abstract: Human papillomavirus (HPV) infection and related diseases are common among men who have sex with men (MSM). The most effective prevention is HPV vaccination. In China, however, men are not included in the HPV vaccination plan. We investigated the intention to initiate HPV vaccination and associated factors among MSM in China. Methods We surveyed 563 unvaccinated MSM aged 18 or older from six cities in China. Participants completed an electronic questionnaire about demographics, knowledge of and attitude towards HPV and HPV vaccine, intention to initiate HPV vaccination, willingness to recommend HPV vaccine to peers, feeling about government policy about HPV vaccination. We used the structural equation modeling (SEM) to analyze factors associated with HPV vaccine intention. Results The knowledge of HPV and HPV vaccine among participants was low. The mean score of knowledge about HPV and HPV vaccine was only 1.59 (range 0-11). The intention to initiate HPV vaccination within 6 months among participants was moderate (43.3% in total, 18.1% for 'very high' and 25.2% for 'above average').

Huang|Ruonan|R| Wang|Zhenyu|Z| Yuan|Tanwei|T| Nadarzynski|Tom|T| Qian|Han-Zhu|HZ| Li|Peiyang|P| Meng|Xiaojun|X| Wang|Guanghui|G| Zhou|Yepeng|Y| Luo|Danyang|D| Wang|Ying|Y| Cai|Yong|Y| Zou|Huachun|H|

Intention
Human Papillomavirus Vaccine
Men who have sex with men