bluuebunny/crossref_metadata_2025 huggingface dataset:
Detection of synthetic cannabinoid adulteration in the unregulated drug supply in three Canadian settings
Authors: Ti Lianping , Tobias Samuel , Maghsoudi Nazlee , Milloy M.‐J. , McDonald Karen , Shapiro Aaron , Beriault Daniel , Stefan Cristiana , Lysyshyn Mark , Werb Daniel
Published: December 2020

Introduction

Novel psychoactive substances (NPS) are increasingly being consumed worldwide, with synthetic cannabinoids and synthetic opioids being the second and third most commonly used NPS, respectively. Certain synthetic cannabinoids can produce significant harms, particularly when used with opioids. The objective of this study was to characterise the presence of synthetic cannabinoids in the unregulated drug supply in three Canadian settings

Methods

In the British Columbia setting, all samples were first analysed at point‐of‐care using combination Fourier‐transform infrared (FTIR) spectroscopy and fentanyl immunoassay strips prior to confirmatory testing using quantitative nuclear magnetic resonance spectroscopy, gas chromatography/mass spectrometry (GC/MS) and/or liquid chromatography/mass spectrometry (LC/MS). In the Toronto, Ontario setting, the samples were analysed directly by GC/MS, LC/MS liquid chromatography‐high resolution/mass spectrometry.

Results

Between January 2018 and December 2019, 38 (2.8%) synthetic cannabinoid samples were detected in the unregulated drug supply (25/909 in British Columbia and 13/440 in Ontario). In British Columbia and Ontario, 76% and 85% of samples, respectively, were expected by individuals to be an opioid. Synthetic cannabinoids detected included AMB‐FUBINACA, AB‐FUBINACA, 5‐fluoro‐MDMB‐PINACA, and 5‐fluoro‐MDMB‐PICA, and largely co‐occurred with fentanyl. In the British Columbia context, Fourier‐transform infrared spectroscopy failed to detect synthetic cannabinoid compounds in almost half (48%) of the samples at point‐of‐care.

Discussion and Conclusions

As point‐of‐care technologies failed to detect these compounds in many occasions, our findings demonstrate the importance of laboratory confirmatory analysis to identify NPS. Given the high risk of harm associated with the consumption of synthetic cannabinoids, further research should investigate the reasons for adulteration.
On opportunities and threats to conserve the phylogenetic diversity of Neotropical palms
Authors: Velazco Santiago José Elías , Svenning Jean‐Christian , Ribeiro Bruno R. , Laureto Livia Maira Orlandi
Published: December 2020

Aim

Palms are an ecologically and societally important plant group, with high diversity in the Neotropics. Here, we estimated the impacts of future climate change on phylogenetic diversity (PD) of Neotropical palms under varying climatic and dispersal scenarios, assessed the effectiveness of the established network of protected areas (PAs) for conserving palms PD today and in 2070, and identified priority areas for the conservation of palm species and their evolutionary history in the face of climate change.

Location

Neotropics.

Methods

We used ecological niche modelling to estimate the distribution of 367 species in the present and for 2070 based on two greenhouse gas emission and two dispersal scenarios. We calculated Faith's PD within each five arc‐minute grid cell to evaluate the effectiveness of PAs relative to null models and used phylogenetic spatial prioritisation analysis to detect priority areas.

Results

We found that even under the most optimistic climatic and dispersal scenarios, the established network of PAs performed poorly in safeguarding palms PD under both current conditions and those projected for 2070. Significant losses in PD inside PAs are expected under future climate conditions, especially if species are unable to disperse to suitable areas. Nevertheless, a modest and strategic increase in the number of PAs could considerably improve the protection of palms PD in the present and 2070.

Main conclusions

The PD of Neotropical palms is poorly represented within the established network of PAs, at both present and in 2070. A higher realised dispersal rates would diminish PD losses inside the network of PAs. The conservation of palm PD can be improved through the expansion of PAs in strategic regions such as the upper portion of the Amazon Basin, Tropical Andes and Mesoamerica.
Specificity of association and plausibility in paediatric neurodisability
Authors: Shortland Adam P
Published: December 2020

This commentary is on the scoping reviews by Williams et al. on pages 263–273 and Walhain et al. on pages 274–286 of this issue.
Transformation of western hemlock (Tsuga heterophylla) tree crowns by dwarf mistletoe (Arceuthobium tsugense, Viscaceae)
Authors: Calkins Stephen J. , Shaw David C. , Lan Yung‐Hsiang
Published: December 2020

Dwarf mistletoes (Arceuthobiumspecies) are arboreal, hemiparasitic plants of conifers that can change the structure and function of the tree crown. Hemlock dwarf mistletoe (Arceuthobium tsugensesubsp.tsugense)principally parasitizes western hemlock (Tsuga heterophylla) and effects 10.8% of all western hemlock trees in Oregon, USA. In this study, we climbed 16 western hemlock trees (age 97–321 years, height 33–54.7 m) across a gradient of infection (0%–100% of branches infected) and measured occurrence of all dwarf mistletoe infections, dwarf mistletoe caused deformities, foliage, branch and crown metrics, and sapwood area. We then modelled over 25 different response variables using linear and generalized linear models with three metrics of severity as explanatory variables: total infection incidence, proportion of all live branches infected, and proportion of all live, infected branches with 33 per cent or more foliage distal to infection. A strong effect of dwarf mistletoe intensification was the reduction of branch foliage and an increase in the proportional amount of foliage distal to infections, with severely infected trees having the majority of foliage distal to infections. Increasing severity led to an apparent crown compaction as crown volumes decreased and became increasingly comprised of deformities. Sapwood area was unrelated to infection severity. Branch length and diameters were unrelated to increasing infection severity despite severely infected branches supporting 1–70 infections. The most severely infected tree had 3,615 individual plants in the crown. Our results suggested that shifts in crown structure and branch deformation, foliage amount, and foliage distal to infection, reflected a likely reduction of capacity for tree growth that coincided with a hypothesized increase in resource demand by dwarf mistletoe plants as infection severity intensified.
An ultrastructural connectomic analysis of a higher‐order thalamocortical circuit in the mouse
Authors: Sampathkumar Vandana , Miller‐Hansen Andrew , Murray Sherman S. , Kasthuri Narayanan
Published: December 2020

Many studies exist of thalamocortical synapses in primary sensory cortex, but much less in known about higher‐order thalamocortical projections to higher‐order cortical areas. We begin to address this gap using genetic labeling combined with large volume serial electron microscopy (i.e., “connectomics”) to study the projection from the thalamic posterior medial nucleus to the secondary somatosensory cortex in a mouse. We injected into this thalamic nucleus a cocktail combining a cre‐expressing virus and one expressing cre‐dependent ascorbate peroxidase that provides an electron dense cytoplasmic label. This “intersectional” viral approach specifically labeled thalamocortical axons and synapses, free of retrograde labeling, in all layers of cortex. Labeled thalamocortical synapses represented 14% of all synapses in the cortical volume, consistent with previous estimates of first‐order thalamocortical inputs. We found that labeled thalamocortical terminals, relative to unlabeled ones: were larger, were more likely to contain a mitochondrion, more frequently targeted spiny dendrites and avoided aspiny dendrites, and often innervated larger spines with spine apparatuses, among other differences. Furthermore, labeled terminals were more prevalent in layers 2/3 and synaptic differences between labeled and unlabeled terminals were greatest in layers 2/3. The laminar differences reported here contrast with reports of first‐order thalamocortical connections in primary sensory cortices where, for example, labeled terminals were larger in layer 4 than layers 2/3 (Viaene et al., 2011a). These data offer the first glimpse of higher‐order thalamocortical synaptic ultrastructure and point to the need for more analyses, as such connectivity likely represents a majority of thalamocortical circuitry.
Neurology training and research in the COVID‐19 pandemic: a survey of the Resident and Research Fellow Section of the European Academy of Neurology
Authors: Cuffaro Luca , Carvalho Vanessa , Di Liberto Giovanni , Klinglehoefer Lisa , Sauerbier Anna , Garcia‐Azorin David , Tábuas‐Pereira Miguel , Vashchenko Nina , Moro Elena , Bassetti Claudio L.A.
Published: December 2020

Background and purpose

The COVID‐19 (SARS‐CoV‐2) outbreak has disrupted residency programmes due to university and hospitals’ priorities to face this emergency at all cost. Most research projects and clinical trials were temporarily stopped or postponed. The Resident and Research Fellow Section (RRFS) of the European Academy of Neurology (EAN) has decided to assess the impact of the COVID‐19 pandemic on neurology training.

Methods

All EAN RRFS members were invited to fill out an online questionnaire of 40 items concerning their clinical involvement during the COVID‐19 emergency, and the impact of the pandemic on their training (Appendix S1).

Results

Of the 227 RRFS members who completed the questionnaire, 222 were from Europe, and of those 111 were from Portugal, Italy or France. Responders highlighted that severe restrictions have been imposed to face this pandemic, including reduction of inpatient beds, prohibition of in‐person visits and limitation to hospital access for patients’ relatives. This was accompanied by an increase in email correspondence and phone calls with 50% of countries allowing telemedicine to reach outpatients. Seventy‐nine per cent of the respondents felt that the pandemic will probably have a serious impact on their training and career.

Conclusion

The pandemic led to a disruption of neurology activities, including medical training and research. The long‐run impact of these changes remains unknown, but it will probably change the way neurology practice and training will be organized for future generations.
Floods increase carbon dioxide and methane fluxes in agricultural streams
Authors: Blackburn Samuel R. , Stanley Emily H.
Published: December 2020

Changes in climate are causing floods to occur more often and more intensely in many parts of the world, including agricultural landscapes of southern Wisconsin (U.S.A.). How flooding and greater flood frequency affect stream carbon dioxide (CO2) and methane (CH4) fluxes and concentrations is not obvious. Thus, we asked how diffusive fluxes of CO2 and CH4 varied over time, particularly in response to floods, in agricultural streams, and what were likely causes for observed flood responses.

We measured concentrations and diffusive fluxes of CO2 and CH4 at 10 stream sites in mixed agricultural and suburban catchments in southern Wisconsin (U.S.A.) during the growing season (March–November) in a year that experienced multiple floods. Habitat, hydrologic, and water chemistry attributes were also quantified to determine likely drivers of changes in gas concentrations and fluxes.

Habitat and water chemistry, as well as CO2 and CH4 concentrations and fluxes were temporally erratic and lacked any seasonality. Carbon dioxide and CH4 concentrations and fluxes were higher during floods along with increased water velocity, turbidity, and dissolved organic carbon and decreases in dissolved oxygen, soft sediment depth, and macrophyte cover.

Increased gas concentrations and fluxes were probably due to flushing of gases from soils, respiration of organic matter in the channel, and increased gas exchange velocities during floods.

Flooding alleviated both supply and transfer limits on CO2 and CH4 emissions in these agricultural streams, and frequent and prolonged flooding during the growing season led to sustained high emissions from these streams. We hypothesise that such persistent increases in emissions during floods may be a common response to high precipitation periods for many agricultural streams.
West Asian colonisation of topmouth gudgeon, Pseudorasbora parva (Teleostei: Gobionidae): Genetic admixture at the crossroad of Europe and east Asia
Authors: Ganjali Zohreh , Esmaeili Hamid Reza , Zarei Fatah , Sayyadzadeh Golnaz , Eagderi Soheil , Gozlan Rodolphe E.
Published: December 2020

Iran is a major freshwater fish diversity hotspot in the Middle East, and is an important zoogeographical area in west Asia, acting as the crossroads and dispersal corridor between several major biogeographical realms of the world. The topmouth gudgeon, Pseudorasbora parva was first recorded in Iran on 6 May 1991 in the Caspian Sea basin and is now widely distributed across the country. Despite widespread distribution in the Iranian inland waters, its invasion history and genetic background remain unknown.

Here, based on the mitochondrial DNA control region (806 bp) sequence variation of 161 P. parva samples collected from 15 Iranian localities and additional sites in Europe and Asia, as well as a cytochrome c oxidase subunit I barcode database (615 bp) including 166 novel and archived sequences, we characterised the pattern of genetic diversity and its colonisation history in Iran.

Our results show the presence of three matrilineal haplotypes in Iran belonging to two distinct lineages: (1) a widespread lineage with a common haplotype found throughout the country and one exclusive haplotype confined to the Mashkid basin, whose origin can be traced back to a single introduction of a small number of propagules from Japan and corresponded to the Iranian introduction of P. parva in the late 1980s; (2) a Chinese lineage represented by a single haplotype found in the Shafarood River of the Caspian Sea basin but also translocated to central Iran, penetrated recently to northern Iran through natural dispersal from Azerbaijan as an extension of the European wave of invasion.

At the global scale, there is less genetic diversity in west Asia than in Europe and the Asian native range. At the local scale, estimates of genetic diversity in Iranian P. parva populations are extremely low but the Caspian Sea and Esfahan basins gained higher diversities from admixture of highly divergent Japanese and Chinese lineages. Our phylogenetic and species delimitation analyses also suggest the existence of multiple putative species in the native range of P. parva and stress the need of an integrative taxonomical approach based on additional morphological and nuclear DNA data.
Challenges and effective routes for formulating and delivery of epidermal growth factors in skin care
Authors: Eskens Olivia , Amin Samiul
Published: December 2020

Epidermal growth factors are important morphogenetic proteins that instruct cell behaviour. They have many inferred applications within regenerative medicine and have shown promising results in skincare treatments. Many growth factors are known to have skin anti‐ageing benefits along with further potential in resolving scarring, acne and other skin disorders. Incorporation of these biologics into skincare formulations has been greatly hindered by low transdermal delivery efficacy, intricate material interactions and protein instability – especially within common cosmetic emulsions. This review explores the cosmeceutical capability of growth factors in skin care, current understandings of constituent interactions and advantageous delivery approaches for more effective topical delivery. The first section highlights the influences growth factor product formulation has on stability and synergy. Current understandings of growth factor formulating techniques in cosmetic products is limited, and the performance of other protein structures is an adequate point of reference. The second section examines emerging drug delivery systems to overcome the challenges of topical growth factor treatment. It is important to consider the coaction and durability of all components in a formulation simultaneously: active ingredients, product format and delivery vehicle, in order to engineer an optimal cosmeceutical product.
Determinants of inequality in Indian regular wage employment, 1993–2012
Authors: MENON Rahul
Published: December 2020

Through the use of decomposition exercises, this article estimates the relative contributions of different factors to inequality among Indian regular wage employees between 1993/94 and 2011/12. It also estimates the contributions of returns to factors and shares of factors determining inequality. The author finds that the single largest contributor among the regular wage workforce in India is access to higher education. However, institutional factors such as union membership and employment in the public sector also play important roles, indicating that inequality cannot be simply reduced to demographic or technical factors, but must also take into account the institutional structure of an economy.
Challenges in diagnosing hydroxychloroquine myopathy during the COVID‐19 pandemic
Authors: Pamphlett Roger , Wang Min‐Xia , Chan Renee CF
Published: December 2020

Hydroxychloroquine is being used for COVID‐19 symptoms and in clinical trials, but can cause a toxic myopathy that leads to muscle weakness. A review of skeletal muscle biopsies from patients with hydroxychloroquine myopathy gives pointers of steps that can be taken to diagnose this toxic myopathy early and help differentiate it from COVID‐19‐related muscle weakness.
Point‐of‐care testing of HbA1c, renal function and lipids in remote or disadvantaged regions
Authors: Handrinos Lena , Januszewski Andrzej S. , Trimble Elisabeth , Donelan Neil , Williams Paul , Jenkins Alicia J.
Published: December 2020

For optimal diabetes management HbA1c, lipid and renal function measurements are key. Suitable point‐of‐care systems can provide such data in remote areas, diabetes camps, disaster relief, small community hospitals and in community screening days in disadvantaged regions. Some systems are currently used in Australian rural, remote and indigenous health services.
Estimation of breeding value, genetic parameters and maternal effects of economic traits in rural male parent line chicken using pedigree relationships in an animal model
Authors: Ullengala Rajkumar , Prince Lawrence Leslie Leo , Haunshi Santosh , Paswan Chandan , Chatterjee Rudranath
Published: December 2020

Breeding value (BV), genetic parameters and additive genetic, and maternal effects were evaluated on growth and production traits utilizing data from eight generations employing animal model in a rural male parent line (PD‐6) chicken at ICAR‐Directorate of Poultry Research, Hyderabad, India. The least squares means (LSM) for body weight (BW) and shank length (SL) up to 6 weeks of age varied significantly (p ≤ .01) among the generations and hatches. BW increased significantly (p ≤ .01) over the generations and decreased with the hatches. Sex also had a significant effect on BW and shank length except for BW at 0 day (BW0). LSM for BW (BW6) and Shank length (SL6) at 6 weeks of age were 598.84 ± 0.79 g and 74.57 ± 0.04 mm, respectively. Males recorded significantly (p ≤ .01) higher BWs and shank length. All the production traits were significantly (p ≤ .01) influenced by the generation effect. The overall LSM for age at sexual maturity (ASM), egg production at 40 weeks (EP40) and egg weight at 40 weeks (EW40) were 164.93 ± 0.23 days, 74.66 ± 0.40 eggs and 54.79 ± 0.08 g, respectively. Model 3 with additive, maternal permanent environmental and residual effects was the appropriate model for BW2, BW4, BW6, SL4 and SL6, whereas Model 4 with maternal effects was the best for BW0. The heritability estimates for BW6 and SL6 were 0.22 ± 0.02 and 0.18 ± 0.02, respectively. Model 1 with additive direct and residual effects was the best appropriate model for all the production traits. The heritability estimates of EP40 and EW40 were 0.16 ± 0.04 and 0.34 ± 0.05, respectively. BW and shank length were highly correlated with significant (p ≤ .05) positive association from different components. The correlation coefficient from direct additive component between egg production and BW40 was negative, while it was positive with less magnitude between egg production and BW20. The egg production and egg weights had a negative association at different ages. BV of SL6, the primary trait of selection, was significant (p ≤ .05) across the generations and increased linearly with an average genetic gain of 1.05 mm per generation. BV of BW6 was also significant (p ≤ .05) and increased linearly as correlated response with an average genetic response of 22.34 g per generation. BV of EP40 showed an increasing trend with a genetic gain of 0.02 eggs per generation. The EW 40 also increased linearly with an average genetic gain of 0.06 g. The average inbreeding coefficient of the population was 0.015. The study concluded that the population was in ideal status with a linearly increasing trend of average BV with negligible inbreeding over the eight generations of selection.
Comparison of electrophysiological characteristics of right‐ and left‐sided Mahaim‐type accessory pathways
Authors: Ozcan Emin Evren , Turan Oguzhan Ekrem , Akdemir Baris , Inevi Umut Dursun , Yilancioglu Resit Yigit , Baskurt Ahmet Anil , Alak Cetin , Bayrak Fatih
Published: December 2020

Aims

Mahaim‐type accessory pathways (MAPs) are generally right‐sided due to the embryological differentiation, but left‐sided localization is also possible. This study aims to compare the clinical and electrophysiological characteristics of right‐ and left‐sided MAPs.

Methods

Of 251 patients diagnosed with AP by electrophysiological study between November 2015 and February 2020, 12 patients with MAP were included (right sided n = 8, left sided n = 4). MAP was diagnosed if; (1) no retrograde conduction; (2) anterograde decremental conduction; (3) adenosine sensitivity; and (4) Mahaim potential at successful ablation site were present.

Results

Ten of twelve MAPs were clustered on the lateral walls of the mitral (n = 3, 75%) and tricuspid annuli (n = 7, 87.5%). Right‐sided MAPs were mostly long pathways extending toward the conduction system whereas left‐sided MAPs were short extending toward the neighboring myocardium. For right‐ and left‐sided APs, the median QRS times were 129 and 156 ms (p = .042), the median VAbl‐RVApex intervals were −12 and 64 ms (p = .007), the median QRS‐V(His) intervals were 16 and 86 ms (p = .120), and the median VAbl‐QRS interval was −8 and 12 ms (p = .017), respectively. Coexistence of dual atrioventricular node physiology was observed only in right‐sided APs (n = 3, 37.5%).

Conclusion

MAPs are more typically located on the right but may rarely be seen on the left. Catheter ablation was associated with high success without complications.
Effective valorization of food wastes and by‐products through pulsed electric field: A systematic review
Authors: Arshad Rai Naveed , Abdul‐Malek Zulkurnain , Roobab Ume , Qureshi Muhammad Imran , Khan Nohman , Ahmad Mohammad Hafizi , Liu Zhi‐Wei , Aadil Rana Muhammad
Published: December 2020

Utilize food waste and by‐products generated from food processing is a developing concern to upgrade economic performance and ensure environmental sustainability. The compounds recovered from the food wastes could have the potential to be employed in different food and biotechnological applications. As a substitute to the conventional method such as Soxhlet extraction, liquid–liquid extraction, and mechanical shaking, the development of green extraction techniques (microwave, ultrasound, and pulsed electric field [PEF]) is seen as a significant step in recovering by‐products from food wastes. Among these, PEF is reported as a novel technique that can decrease solvent usage, heating steps, and extraction time to recover by‐products. The current review covers recent developments in PEF‐based industrial food waste through a systematic literature review. Recent literature was critically evaluated to examine the possibility of this emerging technology in providing sustainable and novel uses of agro‐foods waste and animal‐food waste. Limited literature is available on industrial scale studies of PEF valorization of food waste and food co‐products. Generally, PEF‐based processing is consistently reported as a superior technology that provides high efficiency and better‐quality products due to the low temperature of food compounds. This technique has several spectacular possible applications in food processing methods that provide the food industry with better efficiency and high‐quality products than existing extraction methods.

Practical Applications

This review suggests that PEF treatment of food wastes needs urgent models for optimum processing operation at the industrial level, particularly economic viability under practical working conditions. This innovative processing is generally accepted for more selective, quicker, and sustainable bio‐active compounds but still not satisfactorily verified for industrial applications. There are ethical and economic needs for the management of bio‐waste, and proper legislation appears to be an essential requirement to effectively and fruitfully utilize food waste.
Calcarine as a bridge between brain function and structure in irritable bowel syndrome: A multiplex network analysis
Authors: Chen Nan , Liu Guangyao , Guo Man , Li Yongchao , Yao Zhijun , Hu Bin
Published: December 2020

Background and Aim

Jointly analyzing structural and functional brain networks enables a better understanding of pathological underpinnings of irritable bowel syndrome (IBS). Multiplex network analysis provides a novel framework to study complex networks consisting of different types of connectivity patterns in multimodal data.

Methods

In the present work, we integrated functional and structural networks to a multiplex network. Then, the multiplex metrics and the inner‐layer/inter‐layer hub nodes were investigated through 34 patients with IBS and 33 healthy controls.

Results

Significantly differential multiplex degree in both left and right parts of calcarine was found, and meanwhile, IBS patients lost inner‐layer hub properties in these regions. In addition, the left fusiform was no longer practicing as an inner‐layer hub node, while the right median cingulate acted as a new inner‐layer hub node in the IBS patients. Besides, the right calcarine, which lost its inner‐layer hub identity, became a new inter‐layer hub node, and the multiplex degree of the left hippocampus, which lost its inter‐layer hub identity in IBS patients, was significantly positively correlated with the IBS Symptom Severity Score scores.

Conclusions

Inner‐layer hub nodes of multiplex networks were preferentially vulnerable, and some inner‐layer hub nodes would convert into inter‐layer hub nodes in IBS patients. Besides, the inter‐layer hub nodes might be influenced by IBS severity and therefore converted to general nodes.
Phyllosphere microbiota: Community dynamics and its interaction with plant hosts
Authors: Gong Tianyu , Xin Xiu‐Fang
Published: December 2020

Plants are colonized by various microorganisms in natural environments. While many studies have demonstrated key roles of the rhizosphere microbiota in regulating biological processes such as nutrient acquisition and resistance against abiotic and biotic challenges, less is known about the role of the phyllosphere microbiota and how it is established and maintained. This review provides an update on current understanding of phyllosphere community assembly and the mechanisms by which plants and microbes establish the phyllosphere microbiota for plant health.
Botulinum toxin A as monotherapy for syringoma
Authors: Zaldivar‐Fujigaki José Luis , Achell Nava Lucia
Published: December 2020

Syringoma is a benign adnexal tumor of the skin originating from the eccrine sweat duct. There is a wide variety of treatments, and most of the patients receive multiple unsuccessful therapies. The goal of this report intends to describe a novel technique applicable to syringoma with botulinum toxin A. A 61‐year‐old female patient with localized syringomas in the periocular and upper lip region, with a long‐lasting history, treated with botulinum toxin A 46 IU as monotherapy intradermally distributed and a follow‐up for 8 months. Our patient displayed a significant improvement of the syringomas. Botulinum toxin A is an efficient and safe technique to treat syringomas.
Opioid‐free multimodal analgesia pathway to decrease opioid utilization after cesarean delivery
Authors: Mehraban Shadan S. , Suddle Rahat , Mehraban Shadi , Petrucci Samantha , Moretti Michael , Cabbad Michael , Lakhi Nisha
Published: December 2020

Aim

To evaluate an opioid‐free multimodal analgesic pathway (MAP) to decrease opioid utilization after cesarean delivery (CD) compared to historic data of our institution prior to using MAP for pain management (pre‐MAP).

Methods

The MAP was implemented in three phases from September 2018 to August 2019. Patients received 1000 mg intravenous (IV) acetaminophen with 30 mg IV ketorolac at 0 (arrival time at recovery room), 6, 12 and 18 h of postoperative course. On the 2nd and the 3rd postoperative days, patients were monitored for pain every 6 h by Numeric Pain Intensity Scale (0 = no pain to 10 = severe pain) and administered 600 mg oral ibuprofen for a pain score between 0 and 4, 600 mg oral ibuprofen and/or 650 mg oral acetaminophen for a pain score between 5–6, 1000 mg IV acetaminophen and/or 30 mg of IV or intramuscular ketorolac for a pain score between 7 and 10. Five milligrams of oral oxycodone was reserved for rescue if all protocol options were exhausted. Patients were discharged with 600 mg oral ibuprofen without opioid prescription. Likert surveys measuring patient satisfaction of pain control were administered during phase 3.

Results

Inpatient and outpatient opioid consumption rates were significantly decreased from 45%, 18% to 23.8%, 8.5% after MAP implementation (P‐value <0.001). More than 90% of patients reported that their pain was well controlled and willing to request the same regimen for a future CD.

Conclusion

MAP Implementation after CD significantly reduced inpatient and outpatient opioid consumption compared to pre‐MAP results while maintaining high patients' satisfaction with pain control.
Mass‐spectrometry analysis of the human pineal proteome during night and day and in autism
Authors: Dumas Guillaume , Goubran‐Botros Hany , Matondo Mariette , Pagan Cécile , Boulègue Cyril , Chaze Thibault , Chamot‐Rooke Julia , Maronde Erik , Bourgeron Thomas
Published: December 2020

The human pineal gland regulates day‐night dynamics of multiple physiological processes, especially through the secretion of melatonin. Using mass‐spectrometry‐based proteomics and dedicated analysis tools, we identify proteins in the human pineal gland and analyze systematically their variation throughout the day and compare these changes in the pineal proteome between control specimens and donors diagnosed with autism. Results reveal diverse regulated clusters of proteins with, among others, catabolic carbohydrate process and cytoplasmic membrane‐bounded vesicle‐related proteins differing between day and night and/or control versus autism pineal glands. These data show novel and unexpected processes happening in the human pineal gland during the day/night rhythm as well as specific differences between autism donor pineal glands and those from controls.
Identification and characterization of Cercospora beticola necrosis‐inducing effector CbNip1
Authors: Ebert Malaika K. , Rangel Lorena I. , Spanner Rebecca E. , Taliadoros Demetris , Wang Xiaoyun , Friesen Timothy L. , de Jonge Ronnie , Neubauer Jonathan D. , Secor Gary A. , Thomma Bart P. H. J. , Stukenbrock Eva H. , Bolton Melvin D.
Published: December 2020

Cercospora beticola is a hemibiotrophic fungus that causes cercospora leaf spot disease of sugar beet (Beta vulgaris). After an initial symptomless biotrophic phase of colonization, necrotic lesions appear on host leaves as the fungus switches to a necrotrophic lifestyle. The phytotoxic secondary metabolite cercosporin has been shown to facilitate fungal virulence for several Cercospora spp. However, because cercosporin production and subsequent cercosporin‐initiated formation of reactive oxygen species is light‐dependent, cell death evocation by this toxin is only fully ensured during a period of light. Here, we report the discovery of the effector protein CbNip1 secreted by C. beticola that causes enhanced necrosis in the absence of light and, therefore, may complement light‐dependent necrosis formation by cercosporin. Infiltration of CbNip1 protein into sugar beet leaves revealed that darkness is essential for full CbNip1‐triggered necrosis, as light exposure delayed CbNip1‐triggered host cell death. Gene expression analysis during host infection shows that CbNip1 expression is correlated with symptom development in planta. Targeted gene replacement of CbNip1 leads to a significant reduction in virulence, indicating the importance of CbNip1 during colonization. Analysis of 89 C. beticola genomes revealed that CbNip1 resides in a region that recently underwent a selective sweep, suggesting selection pressure exists to maintain a beneficial variant of the gene. Taken together, CbNip1 is a crucial effector during the C. beticola–sugar beet disease process.
Clinical and pharmacoeconomic evaluation of antifungal prophylaxis with continuous micafungin in patients undergoing allogeneic stem cell transplantation: A six‐year cohort analysis
Authors: Wingen‐Heimann Sebastian M. , Cornely Oliver A. , Vehreschild Maria J.G.T. , Wisplinghoff Hilmar , Franke Bernd , Schons Max , von Bergwelt‐Baildon Michael , Scheid Christof , Vehreschild Jörg Janne
Published: December 2020

Background

Patients undergoing allogeneic stem cell transplantation (aSCT) are at high risk to develop an invasive fungal disease (IFD). Optimisation of antifungal prophylaxis strategies may improve patient outcomes and reduce treatment costs.

Objectives

To analyse the clinical and economical impact of using continuous micafungin as antifungal prophylaxis.

Patients/Methods

We performed a single‐centre evaluation comparing patients who received either oral posaconazole with micafungin as intravenous bridging as required (POS‐MIC) to patients who received only micafungin (MIC) as antifungal prophylaxis after aSCT. Epidemiological, clinical and direct treatment cost data extracted from the Cologne Cohort of Neutropenic Patients (CoCoNut) were analysed.

Results

Three hundred and thirteen patients (97 and 216 patients in the POS‐MIC and MIC groups, respectively) were included into the analysis. In the POS‐MIC and MIC groups, median overall length of stay was 42 days (IQR: 35–52 days) vs 40 days (IQR: 35–49 days; p = .296), resulting in median overall costs of €42,964 (IQR: €35,040–€56,348) vs €43,291 (IQR: €37,281 vs €51,848; p = .993), respectively. Probable/proven IFD in the POS‐MIC and MIC groups occurred in 5 patients (5%) vs 3 patients (1%; p = .051), respectively. The Kaplan‐Meier analysis showed improved outcome of patients in the MIC group at day 100 (p = .037) and day 365 (p < .001) following aSCT.

Conclusions

Our study results demonstrate improved outcomes in the MIC group compared with the POS‐MIC group, which can in part be explained by a tendency towards less probable/proven IFD. Higher drug acquisition costs of micafungin did not translate into higher overall costs.
Clinical experience with isavuconazole in healthy volunteers and patients with invasive aspergillosis in China, and the results from an exposure–response analysis
Authors: Zhang Jing , Zhang Yingyuan , Wu Depei , Cao Guoying , Hamed Kamal , Desai Amit , Aram Jalal A. , Guo Xuan , Fayyad Rana , Cornely Oliver A.
Published: December 2020

Background

Isavuconazole is a broad‐spectrum triazole for the treatment of invasive fungal disease (IFD).

Objective

To investigate the clinical experience with isavuconazole in Chinese individuals.

Patients/Methods

Participants were Chinese healthy volunteers from a Phase I pharmacokinetics (PK) and safety study of single/multiple doses of isavuconazole (n = 36) and Chinese patients from the global Phase III SECURE study that assessed safety and efficacy of isavuconazole vs voriconazole for IFD treatment (n = 26).

Results

No clinically relevant differences in PK were found between Chinese and Western participants, although exposure was increased in Chinese volunteers. Treatment‐emergent adverse events (TEAEs) were reported in 75.0% of healthy volunteers, many of which were infusion‐related. No serious AEs were reported. In SECURE, findings in Chinese patients (n = 26) were similar to the global population. For patients who received ≥1 dose of study drug, allcause mortality from first dose to Day 42 was 10.0% (1/10) with isavuconazole and 25.0% (4/16) with voriconazole (treatment difference [95% confidence interval, CI]: −15.0% [−43.2%, 13.2%]). Overall response at the end of treatment for patients with proven/probable IFD was 25.0% and 16.7% with isavuconazole and voriconazole, respectively (treatment difference [95% CI] −8.3% [−60.2%, 43.5%]). Isavuconazole was associated with lower incidence of hepatobiliary, eye, skin, subcutaneous tissue and psychiatric disorders compared with voriconazole and lower incidence of treatment‐related TEAEs, serious TEAES or death overall.

Conclusions

Although further research is required, this study demonstrated a favourable risk–benefit profile of isavuconazole in Chinese patients.
Self‐determination and a shattered star: Statehood and national identity in the Somali Horn of Africa
Authors: Chonka Peter , Healy Sally
Published: December 2020

This article explores the articulation—in different forms, at different periods, and by different actors—of ‘national self‐determination’ in Somalia and across the Somali‐speaking regions of the Horn of Africa. It explores how this concept can be understood in the context of protracted political fragmentation in Somalia—considering unresolved debates over the ideological foundations of state reconstruction, disagreements about the suitability of federalism, aspirations for the recognition of an independent Republic of Somaliland, and the distinctive trajectory of the Somali Regional State in Ethiopia. Taking a comparative, cross‐border and wide‐angled historical approach, the article argues that ideas of an ethno‐linguistically, culturally and religiously defined Somali ‘nation’ continue to coexist (and be reproduced, updated and used) within an environment of extreme political fragmentation and across multiple ‘state’ boundaries. This argument is made through comparative analysis of contemporary examples of the performance of Somali state and nationalist identities within and beyond the region and the distinctive transnational Somali‐language media environment within which these ideas circulate and compete.
Introduction: Transformation of nationalism and diaspora in the digital age
Authors: Yusupova Guzel , Rutland Peter
Published: December 2020

This introduction to the four papers that make up this themed section locates them in the wider theoretical perspective from which they originate, and highlights the importance of taking into account digital media and technologies as an independent factor that significantly transforms contemporary nationalisms and social identities. Digital media has intensified and accelerated the relationship between culture and politics. It offers new ways of community‐building and identity‐making: both top‐down and bottom‐up, both within the nation‐state and beyond its borders. New research will hopefully explore the complex ways in which both elite and lay understanding and practice of nationalism are evolving in competition and collaboration with each other.
Bilateral visual acuity reduction in a child with Marfan syndrome: Is there a pathogenetic role for optic nerve dural ectasia?
Authors: Trimboli Michele , Tagliente Maria , Troisi Letizia , Manieri Sergio
Published: December 2020

Marfan's syndrome (MFS) is a genetic disorder of the connective tissue diagnosed according to international defined criteria, including spinal dural ectasia. MFS is clinically heterogeneous, with infrequently reported neurological complications. To date, little is known about the occurrence of visual acuity reduction in MFS. We report a case of bilateral visual acuity reduction in a child with MFS, in which magnetic resonance imaging of the brain showed bilateral optic nerve dural ectasia. Could optic nerve dural ectasia may have any role in MFS visual acuity reduction pathogenesis?
Comparative genomics reveals dynamic genome evolution in host specialist ectomycorrhizal fungi
Authors: Lofgren Lotus A. , Nguyen Nhu H. , Vilgalys Rytas , Ruytinx Joske , Liao Hui‐Ling , Branco Sara , Kuo Alan , LaButti Kurt , Lipzen Anna , Andreopoulos William , Pangilinan Jasmyn , Riley Robert , Hundley Hope , Na Hyunsoo , Barry Kerrie , Grigoriev Igor V. , Stajich Jason E. , Kennedy Peter G.
Published: December 2020

While there has been significant progress characterizing the ‘symbiotic toolkit’ of ectomycorrhizal (ECM) fungi, how host specificity may be encoded into ECM fungal genomes remains poorly understood.

We conducted a comparative genomic analysis of ECM fungal host specialists and generalists, focusing on the specialist genus Suillus. Global analyses of genome dynamics across 46 species were assessed, along with targeted analyses of three classes of molecules previously identified as important determinants of host specificity: small secreted proteins (SSPs), secondary metabolites (SMs) and G‐protein coupled receptors (GPCRs).

Relative to other ECM fungi, including other host specialists, Suillus had highly dynamic genomes including numerous rapidly evolving gene families and many domain expansions and contractions. Targeted analyses supported a role for SMs but not SSPs or GPCRs in Suillus host specificity. Phylogenomic‐based ancestral state reconstruction identified Larix as the ancestral host of Suillus, with multiple independent switches between white and red pine hosts.

These results suggest that like other defining characteristics of the ECM lifestyle, host specificity is a dynamic process at the genome level. In the case of Suillus, both SMs and pathways involved in the deactivation of reactive oxygen species appear to be strongly associated with enhanced host specificity.
Erythrocyte transketolase activity coefficient (ETKAC) assay protocol for the assessment of thiamine status
Authors: Jones Kerry S. , Parkington Damon A. , Cox Lorna J. , Koulman Albert
Published: December 2020

Vitamin B1 (thiamine) is an essential nutrient that acts as a cofactor for a number of metabolic processes, particularly in energy metabolism. Symptoms of classic thiamine deficiency are recognized as beriberi, although clinical symptoms are nonspecific and recognition of subclinical deficiency is difficult. Therefore, reliable biomarkers of thiamine status are required. Thiamine diphosphate is a cofactor for transketolase, including erythrocyte transketolase (ETK). The ETK activity assay as an indirect, functional marker of thiamine status has been used for over 50 years. The ETK activity assay provides a sensitive and specific biomarker of thiamine status; however, there is a lack of consensus over the cutoffs for deficiency, partly due to a lack of assay harmonization. Here, we provide a step‐by‐step protocol for the measurement of ETK activity and the calculation of the ETK activity coefficient, including detailed explanations of equipment and chemicals required and guidance for quality control procedures. Harmonization of the protocol will provide the basis for the development of internationally recognized cutoffs for thiamine insufficiency. The establishment of quality control materials and a quality assurance scheme are recommended to provide reliability. This will ensure that the ETK activity assay remains an important method for the assessment of thiamine status.
Evidence for shared genetics between physical activity, sedentary behaviour and adiposity‐related traits
Authors: Schnurr Theresia M. , Stallknecht Bente M. , Sørensen Thorkild I.A. , Kilpeläinen Tuomas O. , Hansen Torben
Published: December 2020

Observational, cross‐sectional and longitudinal studies showed that physical activity and sedentary behaviour are associated with adiposity‐related traits, apparently in a bidirectional manner. Physical activity is also suggested to suppress the genetic risk of adiposity. Since phenotypic associations with genetic variants are not subject to reverse causation or confounding, they may be used as tools to shed light on cause and effect in this complex interdependency. We review the evidence for shared genetics of physical activity and adiposity‐related traits and for gene‐by‐physical activity interactions on adiposity‐related traits in human studies. We outline limitations, challenges and opportunities in studying and understanding of these relationships. In summary, physical activity and sedentary behaviour are genetically correlated with body mass index and fat percentage but may not be correlated with lean body mass. Mendelian randomisation analyses show that physical activity and sedentary behaviour have bidirectional relationships with adiposity. Several studies suggest that physical activity suppresses genetic risk of adiposity. No studies have yet tested whether adiposity enhances genetic predisposition to sedentariness. The complexity of the comprehensive causal model makes the assessment of the single or combined components challenging. Substantial progress in this field may need long‐term intervention studies.
Inflammasome dysregulation in human gingival fibroblasts in response to periodontal pathogens
Authors: Aral Kübra , Milward Michael R. , Cooper Paul R.
Published: December 2020

Objective

Uncontrolled production of Interleukin‐1β (IL‐1β), a major proinflammatory cytokine, is associated with tissue destruction in periodontal disease. IL‐1β production is controlled by inflammasomes which are multiprotein regulatory complexes. The current study aimed to elucidate potential regulatory pathways by monitoring the effects of periodontal pathogens Fusobacterium nucleatum (Fn) and Porphyromonas gingivalis (Pg) on inflammasomes and their regulators in human gingival fibroblasts (HGFs) in vitro.

Methods

HGFs were exposed to Fn and Pg alone or in combination for 24 hr at a multiplicity of infection of 100, ±30 min exposure with 5 mM adenosine triphosphate (ATP) incubation. Gene expression of NLRP3 and AIM2, inflammasome regulatory proteins POP1, CARD16 and TRIM16, and inflammasome components ASC and CASPASE 1, and IL‐1β, were evaluated by RT‐PCR. Pro‐ and mature IL‐1β levels were monitored intracellularly by immunocytochemistry and extracellularly by ELISA.

Results

Fn + ATP significantly upregulated NLRP3, AIM2, IL‐1β, ASC, and CASPASE 1; however, it downregulated POP1 and TRIM16. Pg + ATP downregulated NLRP3, ASC, POP1, but upregulated IL‐1β and CARD16. Pg + Fn+ATP significantly upregulated AIM2, IL‐1β and CARD16, and downregulated POP1, TRIM16, and CASPASE 1. Pg + ATP exposure significantly increased pro‐ and mature IL‐1β production.

Conclusion

Bacterial exposure with ATP may deregulate IL‐1β by dysregulating inflammasomes and their regulators in HGFs.