bluuebunny/crossref_metadata_2025 huggingface dataset:
Respect for Privacy
Authors: Land Molly , Giannoumis Anthony , Kitkowska Aga , Mikhaylova Maria
Published: March 2019

This chapter examines the legal and normative obligations of states under Article 22 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD) to protect individuals with disabilities against unlawful and arbitrary interference with their privacy, both in general and in particular with respect to their personal, health, and rehabilitation information. For persons with disabilities, the right to privacy plays a particularly important role in helping to guarantee rights such as the rights to equality, to freedom from discrimination, to employment, and to education, among others. This is because the right to privacy provides individuals with the right to control information about themselves, including information related to their disability status. The ability to control and limit discovery and disclosure of one’s disability status is essential in helping to protect the individual from discrimination and stigma.
Participation in Political and Public Life
Authors: Plessis Ilze Grobelaar Du , Njau Jehoshaphat
Published: March 2019

This chapter examines Article 29 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). Like all rights provided for under international human rights law, political and public life participation is to be recognized, enjoyed, and exercised without exclusions and/or restrictions. The Working Group to the Ad Hoc Committee of the draft Convention was given a mandate to draft Article 29 CRPD in line with the universal human rights treaties, to provide a protection mechanism that would ensure that persons with disabilities are entitled to the same entitlement to participate in political and public life in the same manner as other persons without disabilities.
Participation in Cultural Life, Recreation, Leisure, and Sport
Authors: Bantekas Ilias , Chow Pok Yin Stephenson , Karapapa Stavroula , Polymenopoulou Eleni
Published: March 2019

This chapter examines Article 30 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). The article covers many, sometimes disparate, issues, although the underlying entitlements are accessibility and availability. One of the cornerstones of Article 30 is access to culture, one of the least studied human rights and its content remains contested. Culture is subject to several limitations, such as censorship, freedom of expression constraints, sensitivities towards religions, and hate speech. Do these limitations apply to the right of access to culture of disabled persons in the same way as they do to their non-disabled counterparts? Paragraph 3 is perhaps the most contentious of all. It suggests that existing intellectual property laws should be construed in such a way as to avoid imposing any unreasonable or discriminatory barriers against persons with disabilities to the enjoyment of their right of access to cultural materials.
Statistics and Data Collection
Authors: Pedersen Mads , Ferretti Federico
Published: March 2019

This chapter examines Article 31 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). It explores how a provision on statistics and research data found its way into a human rights treaty for the first time in the history of international human rights law. It explores the provision’s link with Article 32 on international cooperation and Article 33 on national implementation and monitoring. The chapter also takes a look at the current deficits in statistics and research data on disability, and describes the initiatives taken to set out more robust statistical and research data on disability issues suitable for international comparison. Finally, it highlights some of the initiatives taken and describes best practices on using data as a tool to assess how human rights are lived and experienced by persons with disabilities, with a view to considering how statistics and research data can be used to monitor the implementation of the CRPD.
Report of the Committee
Authors: Treuthart Mary Pat
Published: March 2019

This chapter examines Article 39 of the United Nations Convention on the Rights of Persons with Disabilities (CRPD). Article 39 concerns two aspects of the monitoring and oversight function performed by treaty bodies: reporting and the issuance of general recommendations or comments. The CRPD reporting requirement to the UN General Assembly (UNGA) and the Economic and Social Council is more than just a pro forma procedural matter. The record of events contained in the Committee’s biennial reports provides a vital connection between the States parties, the Committee, and the UNGA. The General Comments, with their elucidation of specific treaty provisions, serve to guide the practice of states parties with respect to the panoply of rights related issues that have an impact on persons with disabilities. More important, these General Comments signal areas that deserve greater attention overall and represent a robust interpretation of the CRPD to protect the human rights of individuals with disabilities.
Persistence of Candida auris on latex and nitrile gloves with transmission to sterile urinary catheters‡
Authors: Jabeen Kauser , Mal Pushpa Bhawan , Tharwani Areeba , Hashmi Mariam , Farooqi Joveria
Published: March 2019

Candida auris’ ability to persist on contaminated gloves and transmit to urinary catheters was evaluated. 105 and 103 cfu/ml suspensions of eight Candida species including C. auris were inoculated on latex and nitrile gloves fingertips and touched on agar surface at different time intervals. Urinary catheter piece, touched by latex glove carrying Candida spp. suspensions at various time intervals, was cultured by roll-plate method. C.auris persisted on latex gloves at both 105 and 103 cfu/ml up to 3 minutes and could be transmitted from both wet and dry contaminated gloves to catheters. Proper glove use with strict hand hygiene should be advocated in settings with ongoing C.auris transmission.
Constraining the evolution of stellar rotation using solar twins
Authors: Lorenzo-Oliveira Diego , Meléndez Jorge , Yana Galarza Jhon , Ponte Geisa , dos Santos Leonardo A , Spina Lorenzo , Bedell Megan , Ramírez Iván , Bean Jacob L , Asplund Martin
Published: March 2019

The stellar rotation versus age relation is commonly considered a useful tool to derive reliable ages for Sun-like stars. However, in the light of Kepler data, the presence of apparently old and fast rotators that do not obey the usual gyrochronology relations led to the hypothesis of weakened magnetic breaking in some stars. In this letter, we constrain the solar rotation evolutionary track using solar twins. Predicted rotational periods as a function of mass, age, [Fe/H], and given critical Rossby number (Rocrit) were estimated for the entire rotational sample. Our analysis favours the smooth rotational evolution scenario and suggests that if the magnetic weakened breaking scenario takes place at all, it should arise after Rocrit ≳ 2.29 or ages ≳5.3 Gyr (at 95 per cent confidence level).
Complete Inactivation of Sebum-Producing Genes Parallels the Loss of Sebaceous Glands in Cetacea
Authors: Lopes-Marques Mónica , Machado André M , Alves Luís Q , Fonseca Miguel M , Barbosa Susana , Sinding Mikkel-Holger S , Rasmussen Marianne Helene , Iversen Maria Refsgaard , Frost Bertelsen Mads , Campos Paula F , da Fonseca Rute , Ruivo Raquel , Castro L Filipe C
Published: March 2019

Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of “gene vestiges” in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.
FOXP1 circular RNA sustains mesenchymal stem cell identity via microRNA inhibition
Authors: Cherubini Alessandro , Barilani Mario , Rossi Riccardo L , Jalal Murtadhah M K , Rusconi Francesco , Buono Giuseppe , Ragni Enrico , Cantarella Giovanna , Simpson Hamish A R W , Péault Bruno , Lazzari Lorenza
Published: March 2019

Stem cell identity and plasticity are controlled by master regulatory genes and complex circuits also involving non-coding RNAs. Circular RNAs (circRNAs) are a class of RNAs generated from protein-coding genes by backsplicing, resulting in stable RNA structures devoid of free 5’ and 3’ ends. Little is known of the mechanisms of action of circRNAs, let alone in stem cell biology. In this study, for the first time, we determined that a circRNA controls mesenchymal stem cell (MSC) identity and differentiation. High-throughput MSC expression profiling from different tissues revealed a large number of expressed circRNAs. Among those, circFOXP1 was enriched in MSCs compared to differentiated mesodermal derivatives. Silencing of circFOXP1 dramatically impaired MSC differentiation in culture and in vivo. Furthermore, we demonstrated a direct interaction between circFOXP1 and miR-17–3p/miR-127–5p, which results in the modulation of non-canonical Wnt and EGFR pathways. Finally, we addressed the interplay between canonical and non-canonical Wnt pathways. Reprogramming to pluripotency of MSCs reduced circFOXP1 and non-canonical Wnt, whereas canonical Wnt was boosted. The opposing effect was observed during generation of MSCs from human pluripotent stem cells. Our results provide unprecedented evidence for a regulatory role for circFOXP1 as a gatekeeper of pivotal stem cell molecular networks.
Multiplexed and tunable transcriptional activation by promoter insertion using nuclease-assisted vector integration
Authors: Brown Alexander , Winter Jackson , Gapinske Michael , Tague Nathan , Woods Wendy S , Perez-Pinera Pablo
Published: March 2019

The ability to selectively regulate expression of any target gene within a genome provides a means to address a variety of diseases and disorders. While artificial transcription factors are emerging as powerful tools for gene activation within a natural chromosomal context, current generations often exhibit relatively weak, variable, or unpredictable activity across targets. To address these limitations, we developed a novel system for gene activation, which bypasses native promoters to achieve unprecedented levels of transcriptional upregulation by integrating synthetic promoters at target sites. This gene activation system is multiplexable and easily tuned for precise control of expression levels. Importantly, since promoter vector integration requires just one variable sgRNA to target each gene of interest, this procedure can be implemented with minimal cloning. Collectively, these results demonstrate a novel system for gene activation with wide adaptability for studies of transcriptional regulation and cell line engineering.
The utility of magnetic resonance imaging for noninvasive evaluation of diabetic nephropathy
Authors: Brown Robert S , Sun Maryellen R M , Stillman Isaac E , Russell Teresa L , Rosas Sylvia E , Wei Jesse L
Published: March 2019

Background

Noninvasive quantitative measurement of fibrosis in chronic kidney disease (CKD) would be desirable diagnostically and therapeutically but standard radiologic imaging is too variable for clinical usage. By applying a vibratory force, tissue shear wave stiffness can be measured by magnetic resonance elastography (MRE) that may correlate with progression of kidney fibrosis. Since decreased kidney perfusion decreases tissue turgor and stiffness, we combined newly available three-dimensional MRE shear stiffness measurements with MR arterial spin labeling (ASL) kidney blood flow rates to evaluate fibrosis in diabetic nephropathy.

Methods

Thirty individuals with diabetes and Stage 0–5 CKD and 13 control individuals without CKD underwent noncontrast MRE with concurrent ASL blood flow measurements.

Results

MRE cortical shear stiffness at 90 Hz was decreased significantly below controls in all CKD stages of diabetic nephropathy. Likewise, ASL blood flow decreased progressively from 480 ± 136 mL/min/100 g of cortical tissue in controls to 302 ± 95, 229 ± 7 and 152 ± 32 mL/min/100 g in Stages 3, 4 and 5 CKD, respectively. A magnetic resonance imaging (MRI) surrogate for the measured glomerular filtration fraction [surrogate filtration fraction = estimated glomerular filtration rate (eGFR)/ASL] decreased progressively from 0.21 ± 0.07 in controls to 0.16 ± 0.04 in Stage 3 and 0.10 ± 0.02 in Stage 4–5 CKD.

Conclusions

In this pilot study, MRI with ASL blood flow rates can noninvasively measure decreasing kidney cortical tissue perfusion and, with eGFR, a decreasing surrogate filtration fraction in worsening diabetic nephropathy that appears to correlate with increasing fibrosis. Differing from the liver, MRE shear stiffness surprisingly decreases with worsening CKD, likely related to decreased tissue turgor from lower blood flow rates.
Acute neurotoxicity following vincristine due to Charcot–Marie–Tooth disease in a young child with medulloblastoma
Authors: Kissoon Trisha , Gururangan Sridharan , Sladky John
Published: March 2019

Vincristine (VCR), a microtubule inhibitor that arrests the cell cycle by blocking metaphase of mitosis, is unique among the vinca alkaloids for causing polyneuropathy. Patients with increased risk of VCR neurotoxicity include the elderly and those with prior history of neuropathy-prone medical conditions. Identifying such risk factors prior to the development of neurotoxicity should be a goal prior to VCR administration. Clinicians should obtain a thorough medical and family history of neuropathies in any child scheduled to receive neurotoxic medications to avoid exacerbating an underlying disorder. We report a case of a young child with newly diagnosed medulloblastoma who started treatment on a VCR-containing chemotherapy regimen following surgery and craniospinal radiation. She subsequently developed severe peripheral polyneuropathy and new enhancement of the cranial and nerve roots following a relatively low cumulative dose of VCR and was diagnosed with previously unidentified Charcot–Marie–Tooth disease (CMTD) Type 1A. This case highlights that an evaluation of risk factors should be completed prior to initiation of neurotoxic chemotherapies and advocates for testing for inherited neuropathies such as CMTD even in asymptomatic patients when hereditary neuropathy is suspected.
Ulva prolifera green-tide outbreaks and their environmental impact in the Yellow Sea, China
Authors: Zhang Yongyu , He Peimin , Li Hongmei , Li Gang , Liu Jihua , Jiao Fanglue , Zhang Jianheng , Huo Yuanzi , Shi Xiaoyong , Su Rongguo , Ye Naihao , Liu Dongyan , Yu Rencheng , Wang Zongling , Zhou Mingjiang , Jiao Nianzhi
Published: March 2019

The Ulva prolifera green tides in the Yellow Sea, China, which have been occurring since 2007, are a serious environmental problem attracting worldwide attention. Despite extensive research, the outbreak mechanisms have not been fully understood. Comprehensive analysis of anthropogenic and natural biotic and abiotic factors reveals that human activities, regional physicochemical conditions and algal physiological characteristics as well as ocean warming and biological interactions (with microorganism or other macroalgae) are closely related to the occurrence of green tides. Dynamics of these factors and their interactions could explain why green tides suddenly occurred in 2007 and decreased abruptly in 2017. Moreover, the consequence of green tides is serious. The decay of macroalgal biomass could result in hypoxia and acidification, possibly induce red tide and even have a long-lasting impact on coastal carbon cycles and the ecosystem. Accordingly, corresponding countermeasures have been proposed in our study for future reference in ecosystem management strategies and sustainable development policy.
A useful approach to sensitivity and predictability studies in geophysical fluid dynamics: conditional non-linear optimal perturbation
Authors: Wang Qiang , Mu Mu , Sun Guodong
Published: March 2019

In atmospheric and oceanic studies, it is important to investigate the uncertainty of model solutions. The conditional non-linear optimal perturbation (CNOP) method is useful for addressing the uncertainty. This paper reviews the development of the CNOP method and its computational aspects in recent years. Specifically, the CNOP method was first proposed to investigate the effects of the optimal initial perturbation on atmosphere and ocean model results. Then, it was extended to explore the influences of the optimal parameter perturbation, model tendency perturbation and boundary condition perturbation. To obtain solutions to these optimal perturbations, four kinds of optimization approaches were developed: the adjoint-based method, the adjoint-free method, the intelligent optimization method and the unconstrained optimization method. We illustrate the calculation process of each method and its advantages and disadvantages. Then, taking the Zebiak–Cane model as an example, we compare the CNOPs related to initial conditions (CNOP-Is) calculated by the above four methods. It was found that the dominant structures of the CNOP-Is for different methods are similar, although some differences in details exist. Finally, we discuss the necessity and possible direction for designing a more effective optimization approach related to the CNOP in the future.
Effect of Supplemental Nutrition Assistance Program–Education (SNAP-Ed) on food security and dietary outcomes
Authors: Rivera Rebecca L , Maulding Melissa K , Eicher-Miller Heather A
Published: March 2019

The Supplemental Nutrition Assistance Program–Education (SNAP-Ed) is the nutrition promotion component of SNAP, formerly known as food stamps. SNAP-Ed assists low-income populations in the United States improve dietary intake and reduce food insecurity through nutrition education. This narrative review summarizes current investigations of SNAP-Ed’s effectiveness at improving food security and dietary outcomes, and it can help inform future policy and implementation of the program. There was stronger evidence for SNAP-Ed as an effective means of improving food security (n = 4 reports) than for its effects on nutrition or dietary outcomes (n = 10 reports). Inconsistency in measurement tools and outcomes and a lack of strong study designs characterized the studies that sought to evaluate the effectiveness of SNAP-Ed at improving nutrition or dietary outcomes. Additional rigorous study designs in diverse population groups are needed to strengthen the evidence. In the face of reduced financial SNAP benefits, SNAP-Ed may play an important role in helping to eliminate food insecurity and improve dietary outcomes and, ultimately, the health of low-income Americans.
Recent advances in intestinal alkaline phosphatase, inflammation, and nutrition
Authors: Lallès Jean-Paul
Published: March 2019

In recent years, much new data on intestinal alkaline phosphatase (IAP) have been published, and major breakthroughs have been disclosed. The aim of the present review is to critically analyze the publications released over the last 5 years. These breakthroughs include, for example, the direct implication of IAP in intestinal tight junction integrity and barrier function maintenance; chronic intestinal challenge with low concentrations of Salmonella generating long-lasting depletion of IAP and increased susceptibility to inflammation; the suggestion that genetic mutations in the IAP gene in humans contribute to some forms of chronic inflammatory diseases and loss of functional IAP along the gut and in stools; stool IAP as an early biomarker of incipient diabetes in humans; and omega-3 fatty acids as direct inducers of IAP in intestinal tissue. Many recent papers have also explored the prophylactic and therapeutic potential of IAP and other alkaline phosphatase (AP) isoforms in various experimental settings and diseases. Remarkably, nearly all data confirm the potent anti-inflammatory properties of (I)AP and the negative consequences of its inhibition on health. A simplified model of the body AP system integrating the IAP compartment is provided. Finally, the list of nutrients and food components stimulating IAP has continued to grow, thus emphasizing nutrition as a potent lever for limiting inflammation.
Testing and management for monoclonal gammopathy of uncertain significance and myeloma patients presenting with osteoporosis and fragility fractures
Authors: Nador Guido , Ramasamy Karthik , Panitsas Fotios , Pratt Guy , Sadler Ross , Javaid Muhammad Kassim
Published: March 2019

Multiple myeloma, the second most frequent blood cancer, and its precursor, monoclonal gammopathy of uncertain significance, are associated with an increased risk of fragility fractures. However, current guidelines fail to offer explicit indications for healthcare professionals in terms of testing and thresholds for onward referral. The purpose of this review is to present the association of these conditions and metabolic bone disease and to highlight the importance of considering a diagnosis of monoclonal gammopathy of uncertain significance and myeloma in the context of a secondary fracture prevention assessment and of a multidisciplinary approach in managing these patients.
A Meta-analysis of Retinal Cytoarchitectural Abnormalities in Schizophrenia and Bipolar Disorder
Authors: Lizano Paulo , Bannai Deepthi , Lutz Olivia , Kim Leo A , Miller John , Keshavan Matcheri
Published: March 2019

Background

Schizophrenia (SZ) and bipolar disorder (BD) are characterized by reductions in gray matter and white matter. Limitations in brain imaging have led researchers to use optical coherence tomography (OCT) to explore retinal imaging biomarkers of brain pathology. We examine the retinal layers that may be associated with SZ or BD.

Methods

Articles identified using PubMed, Web of Science, Cochrane Database. Twelve studies met inclusion for acutely/chronically ill patients. We used fixed or random effects meta-analysis for probands (SZ and BD), SZ or BD eyes vs healthy control (HC) eyes. We adjusted for sources of bias, cross-validated results, and report standardized mean differences (SMD). Statistical analysis performed using meta package in R.

Results

Data from 820 proband eyes (SZ = 541, BD = 279) and 904 HC eyes were suitable for meta-analysis. The peripapillary retinal nerve fiber layer (RNFL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 12, SMD = −0.74, −0.51, −1.06, respectively). RNFL thinning was greatest in the nasal, temporal, and superior regions. The combined peripapillary ganglion cell layer and inner plexiform layer (GCL-IPL) showed significant thinning in SZ and BD eyes compared to HC eyes (n = 4, SMD = −0.39, −0.44, −0.28, respectively). No statistically significant differences were identified in other retinal or choroidal regions. Clinical variables were unrelated to the RNFL or GCL-IPL thickness by meta-regression.

Conclusion

The observed retinal layer thinning is consistent with the classic gray- and white-matter atrophy observed on neuroimaging in SZ and BD patients. OCT may be a useful biomarker tool in studying the neurobiology of psychosis.
Masters of the ‘masters of the universe’? Monetary, fiscal and financial dominance in the Eurozone
Authors: Diessner Sebastian , Lisi Giulio
Published: March 2019

The rise of central bankers to the status of new ‘masters of the universe’ has been matched by mounting allegations of political overreach. In the Eurozone, for instance, the European Central Bank has increasingly been accused of straying into the fiscal realm. Why do politically independent central banks engage intensely and publicly with government policies, thereby threatening the neat separation between monetary and fiscal policy that was meant to protect central banks themselves from interference? While existing political economy accounts have focused squarely on the issues of government debt and central bankers’ fears of fiscal dominance, we argue for the emerging role of ‘financial dominance’ throughout the crisis, thereby shedding light on the structural forces that master the new masters of the universe. To this end, we pursue a mixed-methods approach, combining quantitative text analysis techniques with a qualitative understanding of the context in which central banks communicate on fiscal policy.
Unequal policy responsiveness in the Netherlands
Authors: Schakel Wouter
Published: March 2019

Scholars have long recognized that equality in policy responsiveness is potentially undermined by the existence of economic inequality. However, there is still a lack of empirical research testing whether and how this actually occurs, especially outside of the USA. This study takes up the question whether unequal representation also exists in a country that is in some ways a least-likely case, namely the Netherlands. It does so by linking public opinion to policy on 291 potential policy changes between 1979 and 2012. This reveals, first, that policy responsiveness is much stronger for high incomes than for low or median incomes. Second, an exploration of the underlying causal mechanisms finds support for the role of political participation of wealthier versus poorer citizens, while the socioeconomic background of parliamentarians relative to the broader public does not seem to matter. Corporate lobbying may also contribute to unequal responsiveness.
Exploring Genetic Diversity and Signatures of Horizontal Gene Transfer in Nodule Bacteria Associated with Lotus japonicus in Natural Environments
Authors: Bamba Masaru , Aoki Seishiro , Kajita Tadashi , Setoguchi Hiroaki , Watano Yasuyuki , Sato Shusei , Tsuchimatsu Takashi
Published: March 2019

To investigate the genetic diversity and understand the process of horizontal gene transfer (HGT) in nodule bacteria associated with Lotus japonicus, we analyzed sequences of three housekeeping and five symbiotic genes using samples from a geographically wide range in Japan. A phylogenetic analysis of the housekeeping genes indicated that L. japonicus in natural environments was associated with diverse lineages of Mesorhizobium spp., whereas the sequences of symbiotic genes were highly similar between strains, resulting in remarkably low nucleotide diversity at both synonymous and nonsynonymous sites. Guanine-cytosine content values were lower in symbiotic genes, and relative frequencies of recombination between symbiotic genes were also lower than those between housekeeping genes. An analysis of molecular variance showed significant genetic differentiation among populations in both symbiotic and housekeeping genes. These results confirm that the Mesorhizobium genes required for symbiosis with L. japonicus behave as a genomic island (i.e., a symbiosis island) and suggest that this island has spread into diverse genomic backgrounds of Mesorhizobium via HGT events in natural environments. Furthermore, our data compilation revealed that the genetic diversity of symbiotic genes in L. japonicus-associated symbionts was among the lowest compared with reports of other species, which may be related to the recent population expansion proposed in Japanese populations of L. japonicus.
Empoasca papayae (Hemiptera: Cicadellidae)-Mediated Transmission of Papaya Meleira Virus-Mexican Variant in Mexico
Authors: García-Cámara Isabel , Tapia-Tussell Raúl , Magaña-Álvarez Anuar , Cortés Velázquez Alberto , Martín-Mex Rodolfo , Moreno-Valenzuela Oscar , Pérez-Brito Daisy
Published: March 2019

Papaya meleira virus (PMeV) causes sticky disease in Carica papaya in Brazil and Mexico. Despite its economic importance and the need for effective phytosanitary control, it remains unknown whether any insect is the vector of this virus. The aim of this work was to identify potential insect vectors of the PMeV-Mexican variant (PMeV-Mx) and determine whether these potential vectors are capable of transmitting the virus. Adult insects were collected in papaya fields in the south-southeast region of Mexico and were identified morphologically and molecularly. Their abundance and frequency were determined, and quantitative reverse transcription polymerase chain reaction was performed to establish if they carried PMeV-Mx. The Cicadellidae family (Hemiptera) was the most diverse and abundant, and Empoasca papayae was the most abundant species and had the highest virus titers. PMeV-Mx transmission assays were conducted under controlled conditions using E. papayae on C. papaya ‘Maradol’. E. papayae was a carrier of PMeV-Mx at 6 h after exposure, and its viral titer increased with time, peaking at 2.125 pg/μl of PMeV-Mx RNA from 20 ng/µl of cDNA, 5 days after exposure (dae). From 14 days after plants were exposed to insects, PMeV-Mx was detected and quantified in 100% of the evaluated papaya plants, whose viral RNA titer increased from 0.06 (21 dae) to 26.6 pg/μl of PMeV-Mx RNA (60 dae) from 20 ng/µl of cDNA. Three months later, these plants developed sticky disease symptoms, demonstrating that E. papayae is capable of transmitting PMeV-Mx to C. papaya ‘Maradol’.
Red meat allergy in children and adults
Authors: Wilson Jeffrey M. , Platts-Mills Thomas A.E.
Published: March 2019

Purpose of review

To highlight recent advances in our understanding of the clinical features, prevalence, and pathophysiology of red meat allergy.

Recent findings

Allergic reactions to red (i.e. mammalian) meat have historically been considered rare and described primarily in young atopic children. It is now clear that red meat allergy is not uncommon in some parts of the world in other age groups. Strikingly, the majority of these cases relate to specific IgE to galactose-α-1,3-galactose, an oligosaccharide of nonprimate mammals. The mechanism of sensitization in this syndrome relates to bites of certain hard ticks and the clinical reactions often have a delay of 3 to 6 h. An additional form of red meat allergy relates to inhalant sensitization to mammalian proteins. The best characterized example involves cat-sensitized patients with specific IgE to cat serum albumin who can react to ingested pork because of cross-sensitization to pork serum albumin.

Red meat allergy is more common than previously appreciated and relates to at least three different forms that are distinguished by mechanisms of sensitization and have characteristic clinical and immunologic features.
Mental Health Disorders are More Common in Colorectal Cancer Survivors and Associated With Decreased Overall Survival
Authors: Lloyd Shane , Baraghoshi David , Tao Randa , Garrido-Laguna Ignacio , Gilcrease Glynn W. , Whisenant Jonathan , Weis John R. , Scaife Courtney , Pickron Thomas B. , Huang Lyen C. , Monroe Marcus M. , Abdelaziz Sarah , Fraser Alison M. , Smith Ken R. , Deshmukh Vikrant , Newman Michael , Rowe Kerry G. , Snyder John , Samadder Niloy J. , Hashibe Mia
Published: March 2019

Objectives:

To determine the risk and risk factors for mental illness among colorectal cancer (CRC) survivors across short-term and long-term follow-up periods.

Methods:

We used the Utah Cancer Registry to identify CRC survivors diagnosed between 1997 and 2013. Mental health diagnoses were available in electronic medical records and statewide facilities data that were linked by the Utah Population Database. CRC survivors were matched to individuals from a general population cohort. The risk of developing a mental illness was compared between cohorts. The association between mental illness and mortality was also analyzed.

Results:

In total, 8961 CRC survivors and 35,897 individuals in a general population cohort were identified. CRC survivors were at increased risk for any mental health diagnosis at 0 to 2 years (hazard ratio [HR], 3.70; 95% confidence interval [CI], 3.47-3.95), >2 to 5 years (HR, 1.23; 95% CI, 1.09-1.38), and >5 years (HR, 1.20; 95% CI, 1.07-1.36) after cancer diagnosis. CRC survivors were also at increased risk of depressive disorders specifically during the same time periods. At >5 years, CRC survivors still had an increased risk of developing many mental health diagnoses. Factors associated with increased risk of any mental health disorder among CRC survivors included colostomy and Charlson Comorbidity Index of 1+. There was an increased risk of death for CRC survivors diagnosed with any mental health disorder (HR, 2.18; 95% CI, 2.02-2.35) and depression (HR, 2.10; 95% CI, 1.92-2.28).

Conclusions:

CRC survivors are at increased risk for mental health disorders in the short-term and long-term. Survivors who develop mental health disorders also experience decreased survival.
RELAXING NASAL RETINOTOMY TECHNIQUE FOR CLOSURE OF A MACULAR HOLE THAT REOPENED AFTER PRIMARY VITRECTOMY
Authors: Knight Darren , Yu Jeffrey J. , Adrean Sean D.
Published: March 2019

Purpose:

To describe relaxing nasal retinotomy as a technique to achieve closure of a recurrent macular hole.

Methods:

A patient with juxtafoveal telangiectasia presented with recurrent macular hole after primary vitrectomy and internal limiting membrane peel. During repeat surgery, a superonasal retinotomy was performed to allow for release of tangential traction contributing to the macular hole.

Results:

Intraoperative ocular coherence tomography demonstrated decrease in size of the macular hole immediately after retinotomy. At follow-up, both the macular hole and retinotomy site had closed completely.

Conclusion:

In patients with small macular holes that fail primary vitrectomy, nasal relaxing retinotomy can contribute to successful hole closure.
Hemodynamic monitoring in the extracorporeal membrane oxygenation patient
Authors: Krishnan Sundar , Schmidt Gregory A.
Published: March 2019

Purpose of review

Hemodynamic monitoring in ECMO patients requires familiarity with the underlying pathophysiology and circulatory mechanics of extracorporeal flow. This review discusses the various monitoring modalities relevant to the management of patients on venovenous ECMO (VV ECMO) and venoarterial (VA ECMO). We emphasize tools to judge the adequacy of perfusion, predict the response to fluid boluses, measure right ventricular function, assess left ventricular distention (for VA ECMO), and monitor the process of weaning from ECMO. We emphasize how differences between VV ECMO and VA ECMO are reflected in distinct approaches to monitoring.

Recent findings

Point-of-care ultrasound and near-infrared spectroscopy can play a significant role in monitoring of global and regional perfusion.

Recent literature in hemodynamic monitoring of ECMO patients is discussed, with comparison of VV ECMO and VA ECMO. Many common monitoring tools lack validity during ECMO: by taking into account the unique physiology of the ECMO circulation, selected methods can aid in the care of these complex patients.
Genetic causes of surfactant protein abnormalities
Authors: Nogee Lawrence M.
Published: March 2019

Purpose of review

Mutations in genes encoding proteins critical for the production and function of pulmonary surfactant cause diffuse lung disease. Timely recognition and diagnosis of affected individuals is important for proper counseling concerning prognosis and recurrence risk.

Recent findings

Involved genes include those encoding for surfactant proteins A, B, and C, member A3 of the ATP-binding cassette family, and for thyroid transcription factor 1. Clinical presentations overlap and range from severe and rapidly fatal neonatal lung disease to development of pulmonary fibrosis well into adult life. The inheritance patterns, course, and prognosis differ depending upon the gene involved, and in some cases the specific mutation. Treatment options are currently limited, with lung transplantation an option for patients with end-stage pulmonary fibrosis. Additional genetic disorders with overlapping pulmonary phenotypes are being identified through newer methods, although these disorders often involve other organ systems.

Genetic disorders of surfactant production are rare but associated with significant morbidity and mortality. Diagnosis can be made invasively through clinically available genetic testing. Improved treatment options are needed and better understanding of the molecular pathophysiology may provide insights into treatments for other lung disorders causing fibrosis.
Peripheral Downbeat Positional Nystagmus: Apogeotropic Posterior Canal or Anterior Canal BPPV
Authors: Helminski Janet Odry
Published: March 2019

Background and Purpose:

Downbeat nystagmus (DBN) during the Dix-Hallpike test (DHT) suggests excitation of the anterior canal (AC) or inhibition of the posterior canal (PC) underlying benign paroxysmal positional vertigo (BPPV). This case series describes 2 individuals presenting with DBN in positional testing suggestive of a PC BPPV variant termed apogeotropic PC-BPPV and due to inhibition of the PC.

Case Descriptions:

Case 1 illustrates a DBN during positional testing (PC inhibition) that changes to an upbeating nystagmus (PC excitation) representing the otoconial material changing location and direction of movement within the PC. Case 2 describes a canal jam in the nonampullary segment of the PC.

Differential Diagnosis:

Apogeotropic PC-BPPV can cause DBN due to inhibition of the vestibular afferent. Apogeotropic PC-BPPV may be due to a canal jam of debris within the nonampullary segment or cupulolithiasis with debris attached to the inferior-most aspect of the cupula within the PC. It can be difficult to differentiate AC-BPPV from the apogeotropic PC-BPPV variant. In both forms, the affected canal may be provoked in 1 or both positions of the DHT and straight head hanging position. However, in AC-BPPV there may only be a slight or absent torsional component toward the involved ear. In apogeotropic PC-BPPV, a strong torsion away from the involved ear is typically observed. The straight head hanging position may resolve AC-BPPV or convert apogeotropic PC-BPPV to typical PC-BPPV.

These 2 cases illustrate atypical variants of BPPV that clinicians must consider in their interpretation of DBN during positional testing, particularly in the absence of other neurological signs.
Pediatric Abdominal Pain in Children Presenting to the Emergency Department
Authors: Lee Wei Hao , O'Brien Sharon , Skarin Dmitry , Cheek John A. , Deitch Jessica , Nataraja Ramesh , Craig Simon , Borland Meredith L. ,   on behalf of PREDICT
Published: March 2019

Background

Undifferentiated abdominal pain is a common pediatric presentation to the emergency department (ED).

Objectives

The objective of this study was to describe the prevalence of clinically significant abdominal pathology (CSAP) including appendicitis, patterns of imaging and pathology tests, and management and outcomes of children with abdominal pain in ED.

Methods

A prospective multicenter observational cohort pilot study of children under the age of 16 years presenting to 4 Australian EDs with abdominal pain was performed for a 1-month period at each site. The primary outcome was to describe the prevalence of CSAP and appendicitis. Age, sex, length of stay, surgery or interventional procedure, investigations, and analgesia use were recorded.

Results

There were 555 presentations with abdominal pain during the study period with a median age of 9 years (interquartile range, 6–12 years). Eighty-two patients (14.8%; 95% confidence interval, 11.8–17.7) had CSAP, of which 41 (7.4%, 5.2–9.6) had appendicitis. Three hundred forty-eight (62.7%, 58.7–66.7) were discharged directly from ED, and 207 (37.3%, 33.2–41.3) were admitted. Two hundred fifty-five (45.9%, 41.8–50.1) had pathology tests, and 173 (31.2%, 27.3–35.1) had imaging tests in ED. Of those contacted for telephone follow-up, 100 (50.5%, 43.5–57.5) of 198 reported ongoing pain after discharge, and 13.1% (8.4–17.8) had missed over a week of school due to abdominal pain.

Conclusions

The prevalence of CSAP and appendicitis in our study was 14.8% (11.8–17.7) and 7.4% (5.2–9.6), respectively. Fewer than half of patients received blood tests, and a third received imaging during their ED attendance. The presentation of abdominal pain conveys a significant health burden on families with time off school and ongoing symptoms of pain.
Assessment of Pharmacokinetic, Pharmacodynamic Profile, and Tolerance of Gadopiclenol, A New High Relaxivity GBCA, in Healthy Subjects and Patients With Brain Lesions (Phase I/IIa Study)
Authors: Hao Jing , Bourrinet Philippe , Desché Pierre
Published: March 2019

Objectives

The aim of this study was to evaluate the pharmacokinetics, safety profile, and pharmacodynamics of gadopiclenol, a new high relaxivity macrocyclic gadolinium-based contrast agent, in healthy subjects and patients with brain lesions.

Materials and Methods

This was a single ascending dose phase I/IIa study. Phase I was double-blind, randomized, placebo-controlled and included 54 healthy subjects. In each dose group (0.025, 0.05, 0.075, 0.1, 0.2, and 0.3 mmol/kg), 6 subjects received gadopiclenol and 3 received placebo (NaCl 0.9%) in intravenous injection. Phase IIa was open-label and included 12 patients with brain lesions, 3 per dose group (0.05, 0.075, 0.1, and 0.2 mmol/kg). Concentrations were measured in plasma samples collected before administration and over a 24-hour period postadministration and in urine specimens (phase I) collected until 7 days after administration. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacodynamic assessments included a qualitative evaluation of the visualization of brain structures/lesions and quantitative measurements (signal-to-noise ratio, contrast-to-noise ratio) on magnetic resonance imaging. A clinical and biological safety follow-up was performed up to 7 days after administration for phase I and up to 1 day after administration for phase IIa.

Results

In healthy subjects (male, 50%; median age, 26.0 years), the pharmacokinetics of gadopiclenol is considered linear with mean maximum concentration Cmax values ranging from 248.7 to 3916.4 μg/mL. Gadopiclenol was excreted in an unchanged form via the kidneys, eliminated from plasma with a terminal elimination half-life (t1/2) of 1.5 to 2 hours. There was no difference in the pharmacokinetics between males and females. After administration of gadopiclenol, the contrast enhancement scores in brain structures were improved in all dose groups. Similar rates of related adverse events were observed with gadopiclenol (36.1%) and placebo (33.3%). No clinically significant modifications in biochemistry, hematology, urinalysis, electrocardiogram parameters, and vital signs were reported.

In patients (male, 58%; median age, 53.0 years), a similar pharmacokinetic and safety profile was observed, and sufficient contrast enhancement was seen at all tested doses.

Conclusions

The pharmacokinetics of gadopiclenol is dose-independent in healthy subjects and patients with brain lesions. Its good safety profile is in line with that reported for other macrocyclic gadolinium-based contrast agents. Preliminary pharmacodynamic results in patients suggest that gadopiclenol is a promising macrocyclic contrast agent with the potential use of lower dose for clinical routine magnetic resonance imaging scans.

The study is registered on ClinicalTrials.gov under the trial registration number NCT03603106.
Appearance of Florid Cemento-Osseous Dysplasia on SPECT/CT
Authors: Yang Dorothy Daiyi , Ghuman Abeer , Stratton Richard , Hall Margaret , Parthipun Arum
Published: March 2019

Florid cemento-osseous dysplasia, a benign fibro-osseous condition, is diagnosed based on characteristic radiographic appearances of multifocal round or lobulated sclerotic lesions associated with the teeth in multiple quadrants of the jaws. We report a case of a 73-year-old woman who presented with a painless sharp bony area on the right side of her maxilla. SPECT/CT of facial bones demonstrated multifocal intense increased uptake in both the maxilla and mandible, corresponding to ill-defined florid sclerotic periapical lesions seen on CT, in keeping with a classical appearance of florid cemento-osseous dysplasia.
Therapeutic Response to Rituximab in IgG4-Related Hypophysitis Evidenced on 18F-FDG PET and MRI
Authors: Vauchot Fabien , Bourdon Aurélie , Hay Boramy , Mariano-Goulart Denis , Ben Bouallègue Fayçal
Published: March 2019

Baseline 18F-FDG PET and MRI were performed in a patient with IgG4-related hypophysitis, showing a 15-mm hypervascular hypermetabolic lesion with sellar and suprasellar extension. Lack of response after 10 months of first-line corticosteroid therapy was demonstrated on both 18F-FDG PET and MRI. Three months later, after 2 injections of 1 g of rituximab associated with continued corticosteroid therapy, MRI showed substantial shrinkage of the pituitary lesion with minimal residual Gd enhancement, whereas 18F-FDG PET evidenced complete metabolic response. As such, joint 18F-FDG PET and MRI assessment during therapy may have a potential interest for treatment response evaluation in pituitary IgG4-related disease.
Novel advances in monitoring and therapeutic approaches in idiopathic intracranial hypertension
Authors: Mitchell James L. , Mollan Susan P. , Vijay Vivek , Sinclair Alexandra J.
Published: March 2019

Purpose of review

The current article appraises the recent developments in idiopathic intracranial hypertension (IIH), with particular attention to novel therapeutic avenues and advanced clinical assessment and monitoring with optical coherence tomography and telemetric intracranial pressure devices.

Recent findings

The incidence of IIH is increasing. The first consensus guidelines for IIH have been published detailing investigation and management algorithms for adult IIH. Improved understanding, clinical assessment and monitoring are emerging with the use of optical coherence tomography. Intracranial pressure telemetry is providing unique insights into the physiology of raised intracranial pressure in IIH. There are now an increasing number of ongoing clinical trials evaluating weight loss methods and novel targeted therapies, such as 11ß-HSD1 inhibition and Glucagon-like peptide 1 (GLP-1) receptor agonists.

Several studies are evaluating new therapies for IIH. Monitoring techniques are advancing, aiding diagnosis and allowing the clinician to accurately evaluate changes in papilloedema and intracranial pressure.