bluuebunny/crossref_metadata_2025 huggingface dataset:
Modern water: A biocultural approach to water pollution at the Akwesasne Mohawk Nation
Authors: Schell Lawrence M.
Published: November 2019

Objectives

The goal of this article is to review a body of research around water contamination conducted in the Akwesasne Mohawk Nation between 1995 and 2016, place these findings in a biocultural context, and consider implications for a human biology of water.

Methods

This review draws on research projects conducted in partnership with the Akwesasne Mohawk Nation living along the St. Lawrence River as well as published research by others on water contamination at Akwesasne. Quantitative and qualitative methods including toxicological and epidemiological methods, surveys, and ethnographic studies are included.

Results

Pollution of a river with polychlorinated biphenyls (PCBs) contaminated local fish, a major, traditional, food source. Following health advisories to avoid consuming local fish, consumption and PCB levels decreased. PCB levels were negatively associated with health outcomes. In adolescents, higher PCB levels were associated with advanced sexual maturation in females, reduced testosterone in males and reduced thyroxine levels in young adults. Avoiding fish consumption altered traditional dietary patterns and social interactions, generational transmission of knowledge, and relations between generations, all of which impacted cultural forms and may have added to the perceived injustices in this Native American community. Items substituted for fish may have contributed to increasing rates of obesity as well.

Conclusions

Water pollution has immediate direct health consequences as well as cultural impacts related to changed food consumption and altered patterns of social interaction.
Therapeutic Drug Monitoring of Newer Antiepileptic Drugs: A Randomized Trial for Dosage Adjustment
Authors: Aícua‐Rapún Irene , André Pascal , Rossetti Andrea O. , Ryvlin Philippe , Hottinger Andreas F. , Decosterd Laurent A. , Buclin Thierry , Novy Jan
Published: November 2019

Objective

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) is widely established for older generation AEDs, whereas there is limited evidence about newer AEDs. Our aim is to assess the benefit of TDM of newer generation AEDs in epilepsy.

Methods

We performed a randomized, controlled trial comparing systematic with rescue TDM of lamotrigine, levetiracetam, oxcarbazepine, topiramate, brivaracetam, zonisamide, or pregabalin. Participants were adults with epilepsy, in whom treatment with newer generation AEDs was initiated or needed adjustment. In the systematic TDM arm, AED plasma levels were available at each appointment, whereas in the rescue TDM arm, levels were known only if a study endpoint was reached (inefficacy or adverse events). The primary outcome was the proportion of participants followed 1 year without reaching one of the predefined endpoints.

Results

A total of 151 participants were enrolled; global retention in the study was similar in both arms (56% overall, 58% in the systematic, and 53% in the rescue TDM arm,p= 0.6, Cox regression). There was no difference in terms of outcome regarding treatment efficacy or tolerability. Partial adherence of clinicians to TDM (adjusting or not AED dosage based on blood levels) did not explain this lack of benefit.

Interpretation

This study provides class A evidence that systematic drug level monitoring of newer generation AEDs does not bring tangible benefits in the management of patients with epilepsy. Poor correlation between clinical effects and drug levels likely accounts for this finding. However, TDM is useful in several situations, such as pregnancy, as well as when there are compliance issues. ANN NEUROL 2020;87:22–29
Why Most Acute Stroke Studies Are Positive in Animals but Not in Patients: A Systematic Comparison of Preclinical, Early Phase, and Phase 3 Clinical Trials of Neuroprotective Agents
Authors: Schmidt‐Pogoda Antje , Bonberg Nadine , Koecke Mailin Hannah Marie , Strecker Jan‐Kolja , Wellmann Jürgen , Bruckmann Nils‐Martin , Beuker Carolin , Schäbitz Wolf‐Rüdiger , Meuth Sven G. , Wiendl Heinz , Minnerup Heike , Minnerup Jens
Published: November 2019

Objective

To analyze why numerous acute stroke treatments were successful in the laboratory but failed in large clinical trials.

Methods

We searched all phase 3 trials of medical treatments for acute ischemic stroke and corresponding early clinical and experimental studies. We compared the overall efficacy and assessed the impact of publication bias and study design on the efficacy. Furthermore, we estimated power and true report probability of experimental studies.

Results

We identified 50 phase 3 trials with 46,008 subjects, 75 early clinical trials with 12,391 subjects, and 209 experimental studies with >7,141 subjects. Three (6%) phase 3, 24 (32%) early clinical, and 143 (69.08%) experimental studies were positive. The mean treatment effect was 0.76 (95% confidence interval [CI] = 0.70–0.83) in experimental studies, 0.87 (95% CI = 0.71–1.06) in early clinical trials, and 1.00 (95% CI = 0.95–1.06) in phase 3 trials. Funnel plot asymmetry and trim‐and‐fill revealed a clear publication bias in experimental studies and early clinical trials. Study design and adherence to quality criteria had a considerable impact on estimated effect sizes. The mean power of experimental studies was 17%. Assuming a bias of 30% and pre‐study odds of 0.5 to 0.7, this leads to a true report probability of <50%.

Interpretation

Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the stepwise efficacy decline of stroke treatments from experimental studies to phase 3 clinical trials. Even under conservative estimates, less than half of published positive experimental stroke studies are truly positive. ANN NEUROL 2020;87:40–51
TiO2‐PDVB Janus particles enhanced compatibility of titanium dioxide and recycled waste styrofoam
Authors: Chen Shuning , Ai Jie , Chen Jiawen , Lin Jianrong , Chen Qinhui
Published: November 2019

People are always puzzled by “white pollution” in recent decade. Recycling of waste styrofoam as a coating is a good sustainable solution to resolve this problem. However, the poor compatibility between inorganic additives and polymer hinders the application of recycled polystyrene. In this article, anisotropic Janus particles were used to increase the compatibility of titanium dioxide/waste styrofoam coatings. SEM results show that Janus particles can be anchored at the interface between styrofoam and titanium dioxide, increasing the dispersion of titanium dioxide, and improving the compatibility of inorganic particles and organic polymer. The glass‐transition temperature of styrofoam coating increases from 77 °C to 89 °C in titanium dioxide/styrofoam contained 1 wt % of Janus particles, which certified that Janus particles have compatibilization on titanium dioxide/styrofoam coating. Attributing to this compatibilization, the tensile strength of titanium dioxide/styrofoam with 1 wt % of Janus particles rises about 45% compared with titanium dioxide/styrofoam. The yield stress, storage modulus, and viscosity of titanium dioxide/styrofoam contained 1 wt % of Janus particles are the smallest and the closest to Newtonian fluid. Janus particles used in the recycled styrofoam coating is benefit to expand the application of waste styrofoam and the new anisotropic Janus compatibilizer. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48691.
Extreme Anatomy: Gear for the Pioneer
Authors: Smith Timothy D. , Laitman Jeffrey T.
Published: November 2019

This special issue of The Anatomical Record explores extravagant adaptions that vertebrates have evolved from their base groups to survive in the most challenging environments. The special issue stems from a symposium entitled “Extreme Anatomy: Living beyond the edge,” which was held April 23, 2017, at the annual meeting of the American Association of Anatomists, (now called the American Association for Anatomy), in Chicago, IL. In part 1 of this issue, we encounter fossorial mammals and cave‐dwelling fish and salamanders that have reduced visual systems accompanied by a variety of mechanosensory adaptations. In rivers and seas, teeth may not suffice in the pursuit of prey: aquatic vertebrates are adorned with armor or weaponry or elaborate keratinous sieves. As vertebrates exploit a great diversity of niches, selection has favored a dizzying array of specialized sensory and locomotor adaptions for deep diving, rapid flight, and navigation through dark and complex settings. Each special adaptation, some seemingly quite “extreme” deviations from an original Bauplan, becomes a tool for a pioneer‐like diversification of vertebrates. Anat Rec, 2019. © 2019 American Association for Anatomy
Manipulating 2D Few‐Layer Metal Sulfides as Anode Towards Enhanced Sodium‐Ion Batteries
Authors: Lai Wei‐Hong , Wang Yun‐Xiao , Wang Jia‐Zhao , Chou Shu‐Lei , Dou Shi‐Xue
Published: November 2019

High‐quality anodes are very important for the future generations of rechargeable sodium‐ion batteries (SIBs). Metal sulfides (MSs) as a promising anode have attract tremendous attentions and shown impressive results in terms of versatile material species, low‐cost raw materials, and excellent electrochemical performance. In particular, the unique 2D few‐layer structure of MSs provides a new view for overcoming some challenges appeared on anodic electrodes, such as volume change, structure collapse, high‐rate capability, and confinement of phase‐variation of MSs. Here, we review some of the recent scientific advances in 2D MSs, including the synthetic strategies, electronic structure, and electro‐chemical performance on SIBs.
Emphasize clear, thoughtful communications for handling sexual misconduct reports
Authors: O'Brien Timothy
Published: November 2019

You don't have to look very far to find yet another story about allegations of sexual assault or harassment within a college athletics department. The stories range from alleged rampant sexual misconduct to expulsions of student‐athletes for such conduct to various criminal prosecutions related to the same. The facts of many of these cases are obviously offensive and demand immediate, swift case processing and justice. In certain other cases, however, there's been an unfortunate rush to judgment before discovering all the relevant facts and true context.
Reduce injuries, limit liability by applying interassociation recommendations
Authors: Hanson Hayley , James A.J.
Published: November 2019

The National Collegiate Athletic Association's Sport Science Institute and the College Athletic Trainers’ Society recently published a helpful document, “Interassociation Recommendations: Preventing Catastrophic Injury and Death in Collegiate Athletes.”
Build administrator‐to‐coach relationship to boost success
Authors: McCarthy Claudine
Published: November 2019

Athletics administrators play a key role in ensuring the success of coaches. But it takes an investment in building a relationship with coaches and the initiative to intentionally build coaches up. That's according to a panel of athletics directors who spoke at the annual convention for the National Association of Division III Athletic Administrators. Here's a closer look at how each of them have made strides in coaching the coaches at their institutions.
Impact of chronic thrombocytopenia on in‐hospital outcomes and healthcare resource utilization after transcatheter aortic valve replacement
Authors: Fugar Setri , Behnamfar Omid , Okoh Alexis K. , Alabre Alisha F. , Salia Soziema , Kosinski Mark , Mahmood Ali , Jolly Neeraj , Doukky Rami , Kavinsky Clifford J.
Published: November 2019

Background

There is little data on the impact of chronic thrombocytopenia (CTP) on outcomes after transcatheter aortic valve repair (TAVR). Most studies are from single centers and mostly focused on postprocedure thrombocytopenia.

Objectives

This study sought to report on the impact of CTP (>1 year) on in‐hospital outcomes and healthcare resource utilization after TAVR.

Methods

From the National Inpatient Sample (NIS) between 2012 and 2015, we identified patients with CTP who underwent TAVR. A 1:1 propensity‐matched cohort was created to examine in‐hospital outcomes in patients with and without CTP. The primary outcome was in‐hospital mortality. Secondary outcomes included postprocedure complications, length of stay, total cost, and discharge disposition.

Results

A matched pair of 4,300 patients with and without CTP were identified. Patients with CTP had higher in‐hospital mortality as compared to no CTP patients (6.0 vs. 3.3%, p‐value .007), increased postprocedure hemorrhage, platelet and blood transfusion, vascular complications, postop sepsis, and acute kidney injury. With regards to resource utilization, CTP patients had a longer length of stay, higher total cost and were more likely to be discharged to a facility (34.1 vs. 27.6%) other than home (All, p‐value <.001). Subanalysis, however, revealed this difference in resource utilization was seen when patients developed postprocedure complications.

Conclusion

This study demonstrated higher risk of in‐hospital mortality, perioperative complications, and healthcare resource utilization in patients with baseline CTP undergoing TAVR. Further studies are required to investigate ways to improve the management of these patients.
A systematic review of randomized trials comparing double versus triple antithrombotic therapy in patients with atrial fibrillation undergoing percutaneous coronary intervention
Authors: Sullivan Alexander E. , Nanna Michael G. , Rao Sunil V. , Cantrell Sarah , Gibson C. Michael , Verheugt Freek W. A. , Peterson Eric D. , Lopes Renato D. , Alexander John H. , Granger Christopher B. , Yee Megan K. , Kong David F.
Published: November 2019

Background

Prior randomized controlled trials (RCT) evaluating the optimal antithrombotic therapies for patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been powered to evaluate ischemic outcomes. We compared double therapy with oral anticoagulation (OAC) and a P2Y12 inhibitor to triple therapy with an OAC + dual antiplatelet therapy in patients with AF requiring PCI.

Methods

Using PRISMA guidelines, we searched for RCTs including patients with AF as an indication for OAC and undergoing PCI or medical management of acute coronary syndrome. The results were pooled using fixed‐effects and random‐effects models to estimate the overall effect of double therapy versus triple therapy on ischemic and bleeding outcomes.

Results

We identified four RCTs, comprising 10,238 patients (5,498 double therapy, 4,740 triple therapy). Trial‐reported major adverse cardiovascular events were similar between double therapy and triple therapy (fixed effect model OR 1.09, 95% CI 0.94–1.26). However, stent thrombosis (61/5,496 double therapy vs. 33/4738 triple therapy; fixed effect model OR 1.57, 95% CI 1.02–2.40; number needed to treat with triple therapy = 242) favored triple therapy. Bleeding outcomes were less frequent with double therapy (746/5470 vs. 950/4710; fixed effect model OR 0.59, 95% CI 0.53–0.65; number needed to harm with triple therapy = 16), but with significant heterogeneity (Q = 8.33, p = .04; I2 = 64%), as were intracranial hemorrhages (19/5470 vs. 30/4710; fixed effect model OR 0.54, 95% CI 0.31–0.96).

Conclusions

Double therapy in patients with AF requiring OAC following PCI or Acute coronary syndrome has a significantly better safety profile than triple therapy but may be associated with a modest increased risk of stent thrombosis.
Outcome predictors of patients with out of hospital cardiac arrest and immediate coronary angiography
Authors: Almalla Mohammad , Kersten Alexander , Altiok Ertunc , Burgmaier Mathias , Marx Nikolaus , Schröder Jörg
Published: November 2019

Background

Out of hospital cardiac arrest (OHCA) is common and associated with low survival rates. Guidelines propose a fast work‐up after OHCA including coronary angiography (CA) but little is known about the actual outcome of those patients who undergo immediate CA after OHCA with suspected cardiac origin.

Aim

The aim of this retrospective single‐center study was to evaluate the short‐term outcomes and predictors of in‐hospital mortality in patients who underwent immediate CA after OHCA with suspected cardiac origin.

Methods

We included all consecutive patients with OHCA who underwent immediate CA between January 2011 and December 2015. We defined immediate CA after OHCA as angiography within 2 hr after admission.

Results

Two hundred and nineteen consecutive patients with OHCA were included. Fifty six patients (26%) underwent CA without previous return of spontaneous circulation (ROSC) and with ongoing CPR using the LUCAS‐device. One hundred and forty nine patients (67%) died in hospital. Of the 56 patients with CA with ongoing CPR, 55 died and only 1 patient survived to hospital discharge. In a multivariate analysis, older age (OR = 2.03, 95%CI 1.35–3.03; p = .001), initial shockable rhythm (OR = 0.28, 95%CI 0.07–1.13; p = .076), CA with ongoing CPR (OR = 11.63, 95%CI 1.20–122.55; p = .035), and initial arterial pH (OR = 0.008, 95%CI 0.00–0.228; p < .005) remained as independent predictors for in‐hospital mortality.

Conclusions

In this study older age, metabolic derangement on admission, initial nonshockable rhythm and failure to achieve ROSC before admission predicted in‐hospital mortality. While CA with ongoing CPR with the LUCAS‐device was feasible, mortality in patients without previous ROSC was extremely high, questioning whether this approach is medically useful.
Genome Editing with CRISPR‐Cas: An Overview
Authors: Robb G. Brett
Published: November 2019

The understanding and application of clustered regularly interspaced short palindromic repeat (CRISPR) systems and CRISPR‐associated (Cas) nucleases have helped genome editing become a standard laboratory technique. CRISPR‐Cas nucleases are RNA‐programmed DNA‐cutting enzymes that facilitate the introduction of intentional sequence changes into the genomes of experimental cells and organisms. This overview provides a background for genome editing and CRISPR‐Cas nucleases, as well as an overview of the technology used to assess the outcomes of genome editing. © 2019 The Authors.
Concentric vs. eccentric remodelling in heart failure with reduced ejection fraction: clinical characteristics, pathophysiology and response to treatment
Authors: Nauta Jan F. , Hummel Yoran M. , Tromp Jasper , Ouwerkerk Wouter , van der Meer Peter , Jin Xuanyi , Lam Carolyn S.P. , Bax Jeroen J. , Metra Marco , Samani Nilesh J. , Ponikowski Piotr , Dickstein Kenneth , Anker Stefan D. , Lang Chim C. , Ng Leong L. , Zannad Faiez , Filippatos Gerasimos S. , van Veldhuisen Dirk J. , van Melle Joost P. , Voors Adriaan A.
Published: November 2019

Aims

Heart failure is traditionally classified by left ventricular ejection fraction (LVEF), rather than by left ventricular (LV) geometry, with guideline‐recommended therapies in heart failure with reduced ejection fraction (HFrEF) but not heart failure with preserved ejection fraction (HFpEF). Most patients with HFrEF have eccentric LV hypertrophy, but some have concentric LV hypertrophy. We aimed to compare clinical characteristics, biomarker patterns, and response to treatment of patients with HFrEF and eccentric vs. concentric LV hypertrophy.

Methods and results

We performed a retrospective post‐hoc analysis including 1015 patients with HFrEF (LVEF <40%) from the multinational observational BIOSTAT‐CHF study. LV geometry was classified using two‐dimensional echocardiography. Network analysis of 92 biomarkers was used to investigate pathophysiologic pathways. Concentric LV hypertrophy was present in 142 (14%) patients, who were on average older and more likely hypertensive compared to those with eccentric LV hypertrophy. Network analysis revealed that N‐terminal pro‐B‐type natriuretic peptide was an important hub in eccentric hypertrophy, whereas in concentric hypertrophy, tumour necrosis factor receptor 1, urokinase plasminogen activator surface receptor, paraoxonase and P‐selectin were central hubs. Up‐titration of beta‐blockers was associated with a mortality benefit in HFrEF with eccentric but not concentric LV hypertrophy (P‐value for interaction ≤0.001). For angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, the hazard ratio for mortality was higher in concentric hypertrophy, but the interaction was not significant.

Conclusion

Patients with HFrEF with concentric hypertrophy have a clinical and biomarker phenotype that is distinctly different from those with eccentric hypertrophy. Patients with concentric hypertrophy may not experience similar benefit from up.‐titration of angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers and beta‐blockers compared to patients with eccentric hypertrophy.
Sex is power belief and women’s mental health: The mediating roles of self‐objectification and sexual subjectivity
Authors: De Wilde Matthias , Casini Annalisa , Wollast Robin , Demoulin Stéphanie
Published: November 2019

Sex is power belief (SIPB) positively relates to self‐objectification. This research aims at expanding this finding. We propose that SIPB involves an instrumental view of one’s own body (i.e., self‐objectification) that leads women to experience the negative consequences classically associated with self‐objectification. We further suggest that SIPB positively relates to sexual subjectivity—multidimensional sexual self‐perceptions and positive sexual experiences—and that such relation counterbalances some of the negative effects of SIPB. We examine the effect of SIPB on women’s negative eating attitudes and sexual satisfaction, and test the mediating roles of self‐objectification and sexual subjectivity in three studies (N1 = 121, N2 = 296, N3 = 320). Results supported our predictions that beliefs in one’s sexual power lead both to negative (via self‐objectification) and positive (via sexual subjectivity) consequences for women’s mental health. The discussion focuses on the potential consequences of SIPB at both individual and collective levels.
Eleocharis R. Br. (Cyperaceae) in the Coastal Region of Piauí State, Brazil: A Floristic Treatment
Authors: de Andrade Ivanilza Moreira , dos Santos Ellen Silva , Silva Maria Francilene Souza , dos Santos Alessandra Souza , Nascimento Maria Gracelia Paiva , Silva Mariana de Sales , Mayo Simon Joseph
Published: November 2019

A taxonomic survey of the genus Eleocharis R. Br. was carried out in the four municipalities of coastal Piauí state (Cajueiro da Praia, Ilha Grande, Luís Correia and Parnaíba) included in the Parnaíba Delta Environmental Protection Area. The survey was based on the morphological study of newly collected and existing herbarium material. Six species, native but not endemic to Brazil, were recorded: Eleocharis elegans (Kunth) Roem. & Schult., E. filiculmis Kunth, E. flavescens (Poir.) Urb., E. geniculata (L.) Roem. & Schult., E. mutata (L.) Roem. & Schult. and E. subarticulata (Nees) Boeckeler. Eleocharis flavescens and E. subarticulata are new records for Piauí and E. subarticulata also for the Brazilian Northeast. Descriptions, illustrations, identification keys and information on geographic distribution and habitat are presented. The identification key is provided in English and Portuguese.
Versatile anisotropic mesh adaptation methodology applied to pure quantity of interest error estimator. Steady, laminar incompressible flow
Authors: Carrier Alexandre , Deteix Jean , Fortin André
Published: November 2019

We introduce a new flexible mesh adaptation approach to efficiently compute a quantity of interest by the finite element method. Efficiently, we mean that the method provides an evaluation of that quantity up to a predetermined accuracy at a lower computational cost than other classical methods. The central pillar of the method is our scalar error estimator based on sensitivities of the quantity of interest to the residuals. These sensitivities result from the computation of a continuous adjoint problem. The mesh adaptation strategy can drive anisotropic mesh adaptation from a general scalar error contribution of each element. The full potential of our error estimator is then reached. The proposed method is validated by evaluating the lift, the drag, and the hydraulic losses on a 2D benchmark case: the flow around a cylinder at a Reynolds number of 20.
Astaxanthin inhibits aldose reductase activity in Psammomys obesus, a model of type 2 diabetes and diabetic retinopathy
Authors: Benlarbi‐Ben Khedher Maha , Hajri Khouloud , Dellaa Ahmed , Baccouche Basma , Hammoum Imane , Boudhrioua‐Mihoubi Nourhene , Dhifi Wissal , Ben Chaouacha‐Chekir Rafika
Published: November 2019

Astaxanthin (ATX) is a marine carotenoid known for its powerful antioxidant and neuroprotective properties. In this study, we investigated the in vitro and in vivo potential inhibitory effect of ATX on the aldose reductase (AR) activity, a key enzyme in the polyol pathway responsible for the pathogenesis of diabetic complications including diabetic retinopathy (DR). The gerbil Psammomys obesus (P. ob.), an animal model for type 2 diabetes and DR has been used. The erythrocyte and retinal AR activity of P. ob. individuals were, respectively, assessed monthly and at the 7th month during a 7‐month hypercaloric diet (HD) using a NADPH oxidation method. Meanwhile, the body weight and blood glucose of the gerbils were monitored. After 7 months, P. ob. individuals were fed with ATX (4.8 mg/kg of body weight) once a day for 1 week. The results showed that the HD‐fed animals developed significant obesity and hyperglycemia in comparison with controls. Erythrocyte AR activity showed a progressive and significant increase in the HD‐fed group compared with controls. Retinal AR activity was higher in the 7‐month HD‐fed group compared with controls. Erythrocyte AR activity was markedly decreased after ATX‐treatment in vitro and in vivo. These findings suggested that ATX inhibited the erythrocyte AR activity and could be used for DR prevention and/or early treatment.
Effect of storage, washing, and cooking on the stability of five pesticides in edible fungi of Agaricus bisporus: A degradation kinetic study
Authors: Heshmati Ali , Hamidi Mina , Nili‐Ahmadabadi Amir
Published: November 2019

Pesticide residue in food products is one of the most important global health challenges. The current study sought to investigate the changes in pesticides residue levels in Agaricus bisporus under different storage conditions and during washing and cooking. Pesticides analysis was performed using gas chromatography/mass spectrometry (GC‐MS). The results showed that the half‐life (t1/2) of all of the studied pesticides stored at room temperature was lower than refrigerator and freezer temperature. In addition, the greatest reduction of diazinon, malathion, permethrin, propargite, and fenpropathrin was found at a pH of 12, 2, 12, 7, and 9, respectively. Although sodium chloride had no effective impact on pesticide reduction during the same washing times, the removal of pesticides increased as washing time increased. Further, the reduction of pesticides was time‐dependent during the boiling, microwaving, and frying processes. Based on these findings, the stability of insecticides, such as permethrin, malathion, and diazinon, was lower than acaricides, including propargite and fenpropathrin, in various techniques. Therefore, the use of washing solutions with an appropriate pH as well as increased cooking time may reduce the risk of pesticide exposure.
Impact of an intervention to support hearing and vision in dementia: The SENSE‐Cog Field Trial
Authors: Leroi Iracema , Simkin Zoe , Hooper Emma , Wolski Lucas , Abrams Harvey , Armitage Christopher J. , Camacho Elizabeth , Charalambous Anna Pavlina , Collin Fideline , Constantinidou Fofi , Dawes Piers , Elliott Rachel , Falkingham Sue , Frison Eric , Hann Mark , Helmer Catherine , Himmelsbach Ines , Hussain Hannah , Marié Sarah , Montecelo Susana , Thodi Chryssoula , Yeung Wai Kent
Published: November 2019

Objectives

Hearing, vision, and cognitive impairment commonly co‐occur in older adults. Improving sensory function may positively impact outcomes in people with dementia (PwD). We developed a “sensory intervention” (SI) to support hearing and vision in PwD. Here, we report the findings of an international open‐label field trial, and nested case series, to explore the impact of the SI on dementia‐related outcomes.

Methods

This was a home‐based trial conducted in France, England, and Cyprus. Participants were people with mild‐to‐moderate dementia and hearing and/or vision impairment (n = 19) and their study partners (unpaid carers; n = 19). The “basic” SI included a hearing and vision assessment and provision of glasses and/or hearing aids. A subsample received the “extended” SI with additional weekly visits from a sensory support therapist (SST). Exploratory analyses of dementia‐related, health utility and resource utilisation outcomes were performed.

Results

Quality of life (QoL) and sensory functional ability improved. Change in QoL exceeded the threshold for a minimum clinically important difference. There was a modest improvement (in absolute terms) post intervention in behavioural disturbance, self‐efficacy, and relationship satisfaction. Study partner time assisting instrumental activities of daily living (iADL) and supervision decreased by about 22 and 38 hours per month, respectively, although time for personal ADL support increased. Qualitative data supported effectiveness of the intervention: PwD were more socially engaged, less isolated, less dependent on study partners, and had improved functional ability and communication.

Conclusions

These findings support the need for a definitive randomised controlled trial (RCT) to evaluate the effectiveness of the intervention.
Large‐Scale Production of LGR5‐Positive Bipotential Human Liver Stem Cells
Authors: Schneeberger Kerstin , Sánchez‐Romero Natalia , Ye Shicheng , van Steenbeek Frank G. , Oosterhoff Loes A. , Pla Palacin Iris , Chen Chen , van Wolferen Monique E. , van Tienderen Gilles , Lieshout Ruby , Colemonts‐Vroninks Haaike , Schene Imre , Hoekstra Ruurdtje , Verstegen Monique M.A. , van der Laan Luc J.W. , Penning Louis C. , Fuchs Sabine A. , Clevers Hans , De Kock Joery , Baptista Pedro M. , Spee Bart
Published: November 2019

Background and Aims

The gap between patients on transplant waiting lists and available donor organs is steadily increasing. Human organoids derived from leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5)–positive adult stem cells represent an exciting new cell source for liver regeneration; however, culturing large numbers of organoids with current protocols is tedious and the level of hepatic differentiation is limited.

Approach and Results

Here, we established a method for the expansion of large quantities of human liver organoids in spinner flasks. Due to improved oxygenation in the spinner flasks, organoids rapidly proliferated and reached an average 40‐fold cell expansion after 2 weeks, compared with 6‐fold expansion in static cultures. The organoids repopulated decellularized liver discs and formed liver‐like tissue. After differentiation in spinner flasks, mature hepatocyte markers were highly up‐regulated compared with static organoid cultures, and cytochrome p450 activity reached levels equivalent to hepatocytes.

Conclusions

We established a highly efficient method for culturing large numbers of LGR5‐positive stem cells in the form of organoids, which paves the way for the application of organoids for tissue engineering and liver transplantation.
Phase II, 2‐stage, 2‐arm, PIK3CA mutation stratified trial of MK‐2206 in recurrent endometrial cancer
Authors: Myers Andrea P. , Konstantinopoulos Panagiotis A. , Barry William T. , Luo Weixiu , Broaddus Russell R. , Makker Vicky , Drapkin Ronny , Liu Joyce , Doyle Austin , Horowitz Neil S. , Meric‐Bernstam Funda , Birrer Michael , Aghajanian Carol , Coleman Robert L. , Mills Gordon B. , Cantley Lewis C. , Matulonis Ursula A. , Westin Shannon N.
Published: November 2019

Endometrial cancers have high rates of phosphoinositide 3‐kinase (PI3K) pathway alterations. MK‐2206 is an allosteric inhibitor of AKT, an effector kinase of PI3K signals. We hypothesized patients with tumors harboring PIK3CA mutations would be more likely to benefit from MK‐2206 than those without PIK3CA mutation. A Phase II study was performed in patients with recurrent endometrial cancer; all histologies except carcinosarcoma were eligible. Up to two prior chemotherapy lines were permitted, excluding prior treatment with PI3K pathway inhibitors. The first 18 patients were treated with MK‐2206 200 mg weekly. Due to unacceptable toxicity, dose was reduced to 135 mg. Co‐primary endpoints were objective response rate (ORR) and progression‐free survival at 6 months (6moPFS). Thirty‐seven patients were enrolled (one ineligible). By somatic PIK3CA mutation analysis, nine patients were mutant (MT) [one with partial response (PR)/6moPFS, two with 6moPFS]. Twenty‐seven patients were wild‐type (WT) (one PR and four 6moPFS). Most common toxicities were rash (44%), fatigue (41%), nausea (42%) and hyperglycemia (31%). Grade 3 and 4 toxicities occurred in 25 and 17% of patients, respectively. Exploratory analysis found serous histology had greater 6moPFS as compared to all other histologies (5/8 vs. 2/28, p = 0.003). PTEN expression was associated with median time to progression (p = 0.04). No other significant associations with PI3K pathway alterations were identified. There is limited single agent activity of MK‐2206 in PIK3CA MT and PIK3CA WT endometrial cancer populations. Activity was detected in patients with serous histology and due to their poor outcomes warrants further study (NCT01307631).
Evaluation of lipoprotein‐associated phospholipase A2, serum amyloid A, and fibrinogen as diagnostic biomarkers for patients with acute cerebral infarction
Authors: Tao Liang , ShiChuan Wang , DeTai Zhang , Lihua Hu
Published: November 2019

Objective

The aim of this study was to explore the clinical values of combined detection of lipoprotein‐associated phospholipase A2 (Lp‐PLA2), serum amyloid A (SAA), and plasma fibrinogen (FIB) in the diagnosis of acute cerebral infarction (ACI).

Methods

A case‐control study including 100 hospitalized patients with ACI and 47 healthy controls was carried out. The level of Lp‐PLA2, SAA, and FIB was detected, respectively, and their clinical values were analyzed. Carotid lesions and neurological impairment were also analyzed in each patient.

Results

The level of Lp‐PLA2, SAA, and FIB in the ACI group was significantly higher than that of the controls, and the three biomarkers showed a significant positive correlation and were considered as risk factors for ACI. The area under the curve (AUC) for Lp‐PLA2, SAA, and FIB was 0.858, 0.743, and 0.672, respectively. When three biomarkers were used in combination, the AUC was 0.879. Compared with the other groups, the levels of three biomarkers in bilateral carotid plaque ACI group were all significantly higher. In addition, the level of Lp‐PLA2 and SAA in ACI patients with severe neurological impairment was also significantly higher than that of the mild‐to‐moderate group.

Conclusion

Lp‐PLA2 combined with SAA and FIB had a high clinical value for rapid diagnosis and prediction of ACI. These biomarkers were also significantly associated with the formation of bilateral carotid atherosclerotic plaques and the severe neurological impairment in ACI patients.
On sharing one's truth in psychotherapy: Four poems
Authors: Rickey Cindy
Published: November 2019

Four poems selected from the author's A Year in the Life of an Unemployed Poet, reflect various aspects of the therapeutic experience, in particular what is (and is not) revealed by the client as well as the therapist. Sometimes, it is only poetry that can best convey the deepest (and many times darkest) feelings that arise through the transference and countertransference elicited in therapy, especially a therapy that has lasted over a lifetime.
An efficient synthesis of novel heterocyclic systems incorporating coumarin moiety
Authors: El‐Gohary Nasser M. , El‐Kazak Azza M. , Ibrahim Magdy A.
Published: November 2019

Polyfunctional 3‐chloro‐3‐(4‐chlorocoumarin‐3‐yl)prop‐2‐enal (1) used as a precursor for heterocyclic synthesis. Dichloro‐aldehyde 1 was allowed to react with variable nucleophilic reagents, and a diversity of heterocyclic systems linked coumarin moiety at position 3 was synthesized. The reaction of compound 1 with guanidine and cyanoguanidine produced 3‐(pyrimidin‐4‐yl)‐4‐chlorocoumarins 2 and 3. Treating compound 1 with 3‐amino‐1,2,4‐triazole and 2‐aminobenzimidazole yielded triazolo[4,3‐a]pyrimidine 4 and pyrimido[1,2‐a]benzimidazole 5. The treatment of compound 1 with cyanoacetamide, N‐benzyl‐2‐cyanoacetamide, and 1H‐benzimidazolylacetonitrile gave 2(1H)‐pyridones 6, 7 and pyrido[1,2‐a]benzimidazole 8. The reaction of compound 1 with 5‐amino‐3‐methyl‐1H‐pyrazole and 6‐aminouracil afforded pyrazolo[3,4‐b]pyridine 9 and pyrido[2,3‐d]pyrimidine 10, respectively. Compound 1 reacted with ethylenediamine, o‐phenylenediamine, o‐aminophenol, and o‐aminothiophenol leading to 5‐(imidazolylmethyl)chromeno[4,3‐e] [1,4]diazepine (12), 3‐(benzodiazepin/benzoxazepin‐2‐yl)‐4‐chlorocoumarins 13, 14, and 6‐(benzothiazol‐2‐ylmethyl)chromeno[4,3‐b][1,5]benzothiazepine 16, respectively. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.
Quantitative amino acid analysis by liquid chromatography‐tandem mass spectrometry using low cost derivatization and an automated liquid handler
Authors: Phipps William S. , Crossley Eric , Boriack Richard , Jones Patricia M. , Patel Khushbu
Published: November 2019

Amino acid analysis is central to newborn screening and the investigation of inborn errors of metabolism. Ion‐exchange chromatography with ninhydrin derivatization remains the reference method for quantitative amino acid analysis but offers slow chromatography and is susceptible to interference from other co‐eluting compounds. Liquid‐chromatography tandem mass spectrometry (LC‐MS/MS) provides a rapid and highly specific alternative, but sample preparation is frequently laborious and sometimes cost prohibitive. To address these limitations, we validated an LC‐MS/MS method using the aTRAQ Reagents Application Kit with a modified protocol consuming only half reagents. Adequate performance for clinical specimen measurement of 26 amino acids with high clinical relevance was achieved. An automated liquid handler and modified calibration and normalization approaches were used to ensure reproducible assay performance. Linear measurement between 5 and 2000 μM was achieved for most analytes despite use of a small, 10 μl sample size. Overall the method achieved near substantially improved throughput and enabled use of smaller samples volumes for batched analyses of clinical samples.
Assessment of Cerebral Blood Flow Pulsatility and Cerebral Arterial Compliance With 4D Flow MRI
Authors: Holmgren Madelene , Wåhlin Anders , Dunås Tora , Malm Jan , Eklund Anders
Published: November 2019

Background

Four‐dimensional flow magnetic resonance imaging (4D flow MRI) enables efficient investigation of cerebral blood flow pulsatility in the cerebral arteries. This is important for exploring hemodynamic mechanisms behind vascular diseases associated with arterial pulsations.

Purpose

To investigate the feasibility of pulsatility assessments with 4D flow MRI, its agreement with reference two‐dimensional phase‐contrast MRI (2D PC‐MRI) measurements, and to demonstrate how 4D flow MRI can be used to assess cerebral arterial compliance and cerebrovascular resistance in major cerebral arteries.

Study Type

Prospective.

Subjects

Thirty‐five subjects (20 women, 79 ± 5 years, range 70–91 years).

Field Strength/Sequence

4D flow MRI (PC‐VIPR) and 2D PC‐MRI acquired with a 3T scanner.

Assessment

Time‐resolved flow was assessed in nine cerebral arteries. From the pulsatile flow waveform in each artery, amplitude (ΔQ), volume load (ΔV), and pulsatility index (PI) were calculated. To reduce high‐frequency noise in the 4D flow MRI data, the flow waveforms were low‐pass filtered. From the total cerebral blood flow, total PI (PItot), total volume load (ΔVtot), cerebral arterial compliance (C), and cerebrovascular resistance (R) were calculated.

Statistical Tests

Two‐tailed paired t‐test, intraclass correlation (ICC).

Results

There was no difference in ΔQ between 4D flow MRI and the reference (0.00 ± 0.022 ml/s, mean ± SEM, P = 0.97, ICC = 0.95, n = 310) with a cutoff frequency of 1.9 Hz and 15 cut plane long arterial segments. For ΔV, the difference was –0.006 ± 0.003 ml (mean ± SEM, P = 0.07, ICC = 0.93, n = 310) without filtering. Total R was 11.4 ± 2.41 mmHg/(ml/s) (mean ± SD) and C was 0.021 ± 0.009 ml/mmHg (mean ± SD). ΔVtot was 1.21 ± 0.29 ml (mean ± SD) with an ICC of 0.82 compared with the reference. PItot was 1.08 ± 0.21 (mean ± SD).

Data Conclusion

We successfully assessed 4D flow MRI cerebral arterial pulsatility, cerebral arterial compliance, and cerebrovascular resistance. Averaging of multiple cut planes and low‐pass filtering was necessary to assess accurate peak‐to‐peak features in the flow rate waveforms.

Level of Evidence: 2

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2020;51:1516–1525.
MALDI imaging mass spectrometry of β‐ and γ‐crystallins in the ocular lens
Authors: Anderson David M. , Nye‐Wood Mitchell G. , Rose Kristie L. , Donaldson Paul J. , Grey Angus C. , Schey Kevin L.
Published: November 2019

Lens crystallin proteins make up 90% of expressed proteins in the ocular lens and are primarily responsible for maintaining lens transparency and establishing the gradient of refractive index necessary for proper focusing of images onto the retina. Age‐related modifications to lens crystallins have been linked to insolubilization and cataractogenesis in human lenses. Matrix‐assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) has been shown to provide spatial maps of such age‐related modifications. Previous work demonstrated that, under standard protein IMS conditions, α‐crystallin signals dominated the mass spectrum and age‐related modifications to α‐crystallins could be mapped. In the current study, a new sample preparation method was optimized to allow imaging of β‐ and γ‐crystallins in ocular lens tissue. Acquired images showed that γ‐crystallins were localized predominately in the lens nucleus whereas β‐crystallins were primarily localized to the lens cortex. Age‐related modifications such as truncation, acetylation, and carbamylation were identified and spatially mapped. Protein identifications were determined by top‐down proteomics analysis of lens proteins extracted from tissue sections and analyzed by LC‐MS/MS with electron transfer dissociation. This new sample preparation method combined with the standard method allows the major lens crystallins to be mapped by MALDI IMS.
Differences in outcomes between oral anticoagulation “new starters” and “switchers” in patients with nonvalvular atrial fibrillation: A pooled analysis of the AMADEUS and BOREALIS trials
Authors: Bai Ying , Shantsila Alena , Lip Gregory Y. H.
Published: November 2019

Background

To explore differences in outcomes between dose‐adjusted vitamin K antagonists (VKAs) “new starters” and “switchers” in patients with nonvalvular atrial fibrillation (AF).

Methods

A post hoc analysis was performed to assess the outcome differences between VKA “new starters” and “switchers” in AF patients using pooled individual patient data of AMADEUS and BOREALIS trials.

Results

A total of 4169 AF patients were included in the present analysis, which included 1383 “VKA new starters” and 2786 “VKA switchers”. VKA new starters had higher crude rates of all‐cause mortality (P = .035) and cardiovascular death (P = .047) compared to switchers. On multivariable Cox regression analysis, both “new starters” and “switchers” showed nonsignificant trends for different risks of stroke/systemic thromboembolism (SE) (hazard ratio (HR): 1.66, 95%CI: 0.95‐2.90, P = .08), major bleeding (HR: 1.25, 95% CI: 0.73‐2.16, P = .42), and all‐cause death (HR: 1.09, 95% CI: 0.75‐1.57, P = .65). On Kaplan‐Meier analysis, both groups had similar risks of stroke/systemic embolism (P = .09), major bleeding (P = .28), and all‐cause death (P = .06).

Conclusions

In this post hoc analysis of clinical trial patients with AF, “new starters” and “switchers” for VKA initiation had nonstatistically significant rates of trial‐adjudicated thromboembolism, major bleeding, and all‐cause mortality.
Expression profiles of glucosinolate biosynthetic genes in turnip (Brassica rapa var. rapa) at different developmental stages and effect of transformed flavin‐containing monooxygenase genes on hairy root glucosinolate content
Authors: Yang Ya , Hu Yue , Yue Yanling , Pu Yanan , Yin Xin , Duan Yuanwen , Huang Aixia , Yang Yunqiang , Yang Yongping
Published: November 2019

BACKGROUND

Glucosinolates (GSLs) are secondary metabolites, mainly existing in Brassica vegetables. Their breakdown products have health benefits and contribute to the distinctive taste of these vegetables. Because of their high value, there is a lot of interest in developing breeding strategies to increase the content of beneficial GSLs in Brassica species. GSLs are synthesized from certain amino acids and their biological roles depend largely on the structure of their side chains. Flavin‐containing monooxygenase (FMOGS‐OX) genes are involved in the synthesis of these side chains. To better understand GSL biosynthesis, we sequenced the transcriptomes of turnip (Brassica rapa var. rapa) tubers at four developmental stages (S1–S4) and determined their GSL content.

RESULTS

The total GSL content was high at the early stage (S1) of tuber development and increased up to S3, then decreased at S4. We detected 61 differentially expressed genes, including five FMOGS‐OX genes, that were related for GSL biosynthesis among the four developmental stages. Most of these genes were highly expressed at stages S1 to S3, but their expression was much lower at S4. We estimated the effect of the five FMOGS‐OX genes on GSL content by overexpressing them in turnip hairy roots and found that the amount of aliphatic GSLs increased significantly in the transgenic plants.

CONCLUSION

The transcriptome data and characterization of genes involved in GSL biosynthesis, particularly the FMOGS‐OX genes, will be valuable for improving the yield of beneficial GSLs in turnip and other Brassica crops. © 2019 Society of Chemical Industry
Enantioseparation of acetyltropic acid by countercurrent chromatography with sulfobutyl ether‐β‐cyclodextrin as chiral selector
Authors: Qiu Xujun , Sun Wenyu , Wang Chaoyue , Yan Jizhong , Tong Shengqiang
Published: November 2019

Acetyltropic acid is an important synthetic intermediate for preparation of tropane alkaloid derivatives, which can be used as anticholinergic drugs, deliriants, and stimulants. In the present work, acetyltropic acid was successfully enantioseparated by countercurrent chromatography using sulfobutyl ether‐β‐cyclodextrin as chiral selector. A biphasic solvent system composed of n‐butyl acetate/n‐hexane/0.1 mol/L citrate buffer at pH = 2.2 containing 0.1 mol/L of sulfobutyl ether‐β‐cyclodextrin (7:3:10, v/v) was selected, which produced a suitable distribution ratio DS = 1.14, DR = 2.31 and a high enantioseparation factor α = 2.03. Baseline separation was achieved for preparative enantioseparation of 50 mg of racemic acetyltropic acid. A method for chiral analysis of acetyltropic acid by conventional reverse phase liquid chromatography with hydroxylpropyl‐β‐cyclodextrin as mobile phase additive was established, and formation constants of inclusion complex were determined. It was found that different substituted β‐cyclodextrin should be selected for enantioseparation of acetyltropic acid by countercurrent chromatography and reverse phase liquid chromatography.