MyMedR

Displaying publications 21 - 40 of 48 in total

Abstract:

Sort:

Tunability of Pickering particle features of whey protein isolate via remodeling partial unfolding during ultrasonication-assisted complexation with chitosan/chitooligosaccharide

Yu H, Zheng Y, Zhou C, Liu L, Wang L, Cao J, et al.

Carbohydr Polym, 2024 Feb 01;325:121583.
PMID: 38008470 DOI: 10.1016/j.carbpol.2023.121583

The potential of ultrasonication-driven molecular self-assembly of whey protein isolate (WPI) with chitosan (CS)/chitooligosaccharide (COS) to stabilize Pickering emulsions was examined, based on CS/COS ligands-induced partial unfolding in remodeling the Pickering particles features. Multi-spectral analysis suggested obvious changes in conformational structures of WPI due to interaction with CS/COS, with significantly higher unfolding degrees of WPI induced by COS. Non-covalent interactions were identified as the major forces for WPI-CS/COS conjugates. Ultrasonication enhanced electrostatic interaction between CS's -NH3 groups and WPI's -COO- groups which improved emulsification activity and storability of WPI-COS stabilized Pickering emulsion. This was attributed to increased surface hydrophobicity and decreased particle size compared to WPI-CS associated with differential unfolding degrees induced by different saccharide ligands. CLSM and SEM consistently observed smaller emulsion droplets in WPI-COS complexes than WPI-CS/COS particles tightly adsorbed at the oil-water interface. The electrostatic self-assembly of WPI with CS/COS greatly enhanced the encapsulation efficiency of quercetin than those stabilized by WPI alone and ultrasound further improved encapsulation efficiency. This corresponded well with the quantitative affinity parameters between quercetin and WPI-CS/COS complexes. This investigation revealed the great potential of glycan ligands-induced conformational transitions of extrinsic physical disruption in tuning Pickering particle features.
Gelatin based preservation technologies on the quality of food: a comprehensive review

Ying Q, Zhan S, Yu H, Li J, Jia R, Wei H, et al.

Crit Rev Food Sci Nutr, 2024 Jun 07.
PMID: 38850027 DOI: 10.1080/10408398.2024.2361298

Gelatin has played a great potential in food preservation because of its low price and superior film forming characteristics. This review provides a comprehensive overview of the latest research progress and application of gelatin preservation technologies (film, coating, antifreeze peptide, etc.), discussing their preservation mechanisms and efficiency through the viewpoints of quality and shelf life of animal and aquatic products as well as fruits and vegetables. It showed that bioactive and intelligent gelatin-based films exhibit antibacterial, antioxidant, water resistance and pH responsive properties, making them excellent for food preservation. In addition, pH responsive properties of films also intuitively reflect the freshness of food by color. Similarly, gelatin and its hydrolysate can be widely used in antifreeze peptides to reduce the mass loss of food during freezing and extend the shelf life of frozen food. However, extensive works are still required to extend their commercial application values.
Fulltext Mitochondrial Respiration Is Reduced in Atherosclerosis, Promoting Necrotic Core Formation and Reducing Relative Fibrous Cap Thickness

Yu EPK, Reinhold J, Yu H, Starks L, Uryga AK, Foote K, et al.

Arterioscler Thromb Vasc Biol, 2017 12;37(12):2322-2332.
PMID: 28970293 DOI: 10.1161/ATVBAHA.117.310042

OBJECTIVE: Mitochondrial DNA (mtDNA) damage is present in murine and human atherosclerotic plaques. However, whether endogenous levels of mtDNA damage are sufficient to cause mitochondrial dysfunction and whether decreasing mtDNA damage and improving mitochondrial respiration affects plaque burden or composition are unclear. We examined mitochondrial respiration in human atherosclerotic plaques and whether augmenting mitochondrial respiration affects atherogenesis.
APPROACH AND RESULTS: Human atherosclerotic plaques showed marked mitochondrial dysfunction, manifested as reduced mtDNA copy number and oxygen consumption rate in fibrous cap and core regions. Vascular smooth muscle cells derived from plaques showed impaired mitochondrial respiration, reduced complex I expression, and increased mitophagy, which was induced by oxidized low-density lipoprotein. Apolipoprotein E-deficient (ApoE-/-) mice showed decreased mtDNA integrity and mitochondrial respiration, associated with increased mitochondrial reactive oxygen species. To determine whether alleviating mtDNA damage and increasing mitochondrial respiration affects atherogenesis, we studied ApoE-/- mice overexpressing the mitochondrial helicase Twinkle (Tw+/ApoE-/-). Tw+/ApoE-/- mice showed increased mtDNA integrity, copy number, respiratory complex abundance, and respiration. Tw+/ApoE-/- mice had decreased necrotic core and increased fibrous cap areas, and Tw+/ApoE-/- bone marrow transplantation also reduced core areas. Twinkle increased vascular smooth muscle cell mtDNA integrity and respiration. Twinkle also promoted vascular smooth muscle cell proliferation and protected both vascular smooth muscle cells and macrophages from oxidative stress-induced apoptosis.
CONCLUSIONS: Endogenous mtDNA damage in mouse and human atherosclerosis is associated with significantly reduced mitochondrial respiration. Reducing mtDNA damage and increasing mitochondrial respiration decrease necrotic core and increase fibrous cap areas independently of changes in reactive oxygen species and may be a promising therapeutic strategy in atherosclerosis.
Fulltext Genomic evidence for the Chinese mountain cat as a wildcat conspecific (Felis silvestris bieti) and its introgression to domestic cats

Yu H, Xing YT, Meng H, He B, Li WJ, Qi XZ, et al.

Sci Adv, 2021 Jun;7(26).
PMID: 34162544 DOI: 10.1126/sciadv.abg0221

The Qinghai-Tibet Plateau endemic Chinese mountain cat has a controversial taxonomic status, whether it is a true species or a wildcat (Felis silvestris) subspecies and whether it has contributed to cat (F. s. catus) domestication in East Asia. Here, we sampled F. silvestris lineages across China and sequenced 51 nuclear genomes, 55 mitogenomes, and multilocus regions from 270 modern or museum specimens. Genome-wide analyses classified the Chinese mountain cat as a wildcat conspecific F. s. bieti, which was not involved in cat domestication of China, thus supporting a single domestication origin arising from the African wildcat (F. s. lybica). A complex hybridization scenario including ancient introgression from the Asiatic wildcat (F. s. ornata) to F. s. bieti, and contemporary gene flow between F. s. bieti and sympatric domestic cats that are likely recent Plateau arrivals, raises the prospect of disrupted wildcat genetic integrity, an issue with profound conservation implications.
Regulating tumor microenvironments by a lymph node-targeting adjuvant via tumor-specific CTL-derived IFNγ

Xu X, Yi C, Feng T, Ge Y, Liu M, Wu C, et al.

Clin Immunol, 2023 Aug;253:109685.
PMID: 37406980 DOI: 10.1016/j.clim.2023.109685

Inducing tumor-specific T cell responses and regulating suppressive tumor microenvironments have been a challenge for effective tumor therapy. CpG (ODN), the Toll-like receptor 9 agonist, has been widely used as adjuvants of cancer vaccines to induce T cell responses. We developed a novel adjuvant to improve the targeting of lymph nodes. CpG were modified with lipid and glycopolymers by the combination of photo-induced RAFT polymerization and click chemistry, and the novel adjuvant was termed as lipid-glycoadjuvant@AuNPs (LCpG). OVA protein was used as model antigen and melanoma model was established to test the immunotherapy effect of the adjuvant. In tumor model, the antitumor effect and mechanism of LCpG on the response of CTLs were examined by flow cytometry and cell cytotoxicity assay. The effects of LCpG on macrophage polarization and Tregs differentiation in tumor microenvironment were also studied by cell depletion assay and cytokine neutralization assay. We also tested the therapeutic effect of the combination of the adjuvant and anti-PD-1 treatment. LCpG could be rapidly transported to and retained longer in the lymphoid nodes than unmodified CpG. In melanoma model, LCpG controlled both primary tumor and its metastasis, and established long-term memory. In spleen and tumor draining lymphoid nodes, LCpG activated tumor-specific Tc1 responses, with increased CD8+ T-cell proliferation, antigen-specific Tc1 cytokine production and specific-tumor killing capacity. In tumor microenvironments, antigen-specific Tc1 induced by the LCpG promoted CTL infiltration, skewed tumor associated macrophages to M1 phenotype, regulated Treg and induced proinflammatory cytokines production in a CTL-derived IFN-γ-dependent manner. In vivo cell depletion and adoptive transfer experiments confirmed that antitumor activity of LCpG included vaccine was mainly dependent on CTL-derived IFN-γ. The anti-tumor efficacy of LCpG was dramatically enhanced when combined with anti-PD1 immunotherapy. LCpG was a promising adjuvant for vaccine formulation which could augment tumor-specific Tc1 activity, and regulate tumor microenvironments.
Fulltext Identification and genomic analysis of temperate Halomonas bacteriophage vB_HmeY_H4907 from the surface sediment of the Mariana Trench at a depth of 8,900 m

Su Y, Zhang W, Liang Y, Wang H, Liu Y, Zheng K, et al.

Microbiol Spectr, 2023 Sep 20;11(5):e0191223.
PMID: 37728551 DOI: 10.1128/spectrum.01912-23

Viruses play crucial roles in the ecosystem by modulating the host community structure, mediating biogeochemical cycles, and compensating for the metabolism of host cells. Mariana Trench, the world's deepest hadal habitat, harbors a variety of unique microorganisms that have adapted to its extreme conditions of low temperatures, high pressure, and nutrient scarcity. However, our knowledge about isolated hadal phage strains in the hadal trench is still limited. This study reported the discovery of a temperate phage, vB_HmeY_H4907, infecting Halomonas meridiana H4907, isolated from surface sediment from the Mariana Trench at a depth of 8,900 m. To our best knowledge, it is the deepest isolated siphovirus from the ocean. Its 40,452 bp linear dsDNA genome has 57.64% GC content and 55 open reading frames, and it is highly homologous to its host. Phylogenetic analysis and average nucleotide sequence identification reveal that vB_HmeY_H4907 is separated from the isolated phages and represents a new family, Suviridae, with eight predicted proviruses and six uncultured viral genomes. They are widely distributed in the ocean, suggesting a prevalence of this viral family in the deep sea. These findings expand our understanding of the phylogenetic diversity and genomic features of hadal lysogenic phages, provide essential information for further studies of phage-host interactions and evolution, and may reveal new insights into the lysogenic lifestyles of viruses inhabiting the hadal ocean. IMPORTANCE Halomonas phage vB_HmeY_H4907 is the deepest isolated siphovirus from the ocean, and it represents a novel abundant viral family in the ocean. This study provides insights into the genomic, phylogenetic, and ecological characteristics of the new viral family, namely, Suviridae.
Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

Huang Q, Zhao G, Chen Y, Wu P, Li S, Peng C, et al.

J Urol, 2023 Jan;209(1):99-110.
PMID: 36194169 DOI: 10.1097/JU.0000000000002952

PURPOSE: We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest.
MATERIALS AND METHODS: Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed.
RESULTS: Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up.
CONCLUSIONS: Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.
Fulltext LGR5 Activates Noncanonical Wnt Signaling and Inhibits Aldosterone Production in the Human Adrenal

Shaikh LH, Zhou J, Teo AE, Garg S, Neogi SG, Figg N, et al.

J Clin Endocrinol Metab, 2015 Jun;100(6):E836-44.
PMID: 25915569 DOI: 10.1210/jc.2015-1734

CONTEXT: Aldosterone synthesis and cellularity in the human adrenal zona glomerulosa (ZG) is sparse and patchy, presumably due to salt excess. The frequency of somatic mutations causing aldosterone-producing adenomas (APAs) may be a consequence of protection from cell loss by constitutive aldosterone production.
OBJECTIVE: The objective of the study was to delineate a process in human ZG, which may regulate both aldosterone production and cell turnover.
DESIGN: This study included a comparison of 20 pairs of ZG and zona fasciculata transcriptomes from adrenals adjacent to an APA (n = 13) or a pheochromocytoma (n = 7).
INTERVENTIONS: Interventions included an overexpression of the top ZG gene (LGR5) or stimulation by its ligand (R-spondin-3).
MAIN OUTCOME MEASURES: A transcriptome profile of ZG and zona fasciculata and aldosterone production, cell kinetic measurements, and Wnt signaling activity of LGR5 transfected or R-spondin-3-stimulated cells were measured.
RESULTS: LGR5 was the top gene up-regulated in ZG (25-fold). The gene for its cognate ligand R-spondin-3, RSPO3, was 5-fold up-regulated. In total, 18 genes associated with the Wnt pathway were greater than 2-fold up-regulated. ZG selectivity of LGR5, and its absence in most APAs, were confirmed by quantitative PCR and immunohistochemistry. Both R-spondin-3 stimulation and LGR5 transfection of human adrenal cells suppressed aldosterone production. There was reduced proliferation and increased apoptosis of transfected cells, and the noncanonical activator protein-1/Jun pathway was stimulated more than the canonical Wnt pathway (3-fold vs 1.3-fold). ZG of adrenal sections stained positive for apoptosis markers.
CONCLUSION: LGR5 is the most selectively expressed gene in human ZG and reduces aldosterone production and cell number. Such conditions may favor cells whose somatic mutation reverses aldosterone inhibition and cell loss.
Fulltext Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene

Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, et al.

Nat Genet, 2013 Oct;45(10):1160-7.
PMID: 23974870 DOI: 10.1038/ng.2745

Allelic heterogeneity in disease-causing genes presents a substantial challenge to the translation of genomic variation into clinical practice. Few of the almost 2,000 variants in the cystic fibrosis transmembrane conductance regulator gene CFTR have empirical evidence that they cause cystic fibrosis. To address this gap, we collected both genotype and phenotype data for 39,696 individuals with cystic fibrosis in registries and clinics in North America and Europe. In these individuals, 159 CFTR variants had an allele frequency of ł0.01%. These variants were evaluated for both clinical severity and functional consequence, with 127 (80%) meeting both clinical and functional criteria consistent with disease. Assessment of disease penetrance in 2,188 fathers of individuals with cystic fibrosis enabled assignment of 12 of the remaining 32 variants as neutral, whereas the other 20 variants remained of indeterminate effect. This study illustrates that sourcing data directly from well-phenotyped subjects can address the gap in our ability to interpret clinically relevant genomic variation.
Menstrual and Reproductive Factors, Hormone Use, and Risk of Pancreatic Cancer: Analysis From the International Pancreatic Cancer Case-Control Consortium (PanC4)

Lujan-Barroso L, Zhang W, Olson SH, Gao YT, Yu H, Baghurst PA, et al.

Pancreas, 2016 11;45(10):1401-1410.
PMID: 27088489

OBJECTIVES: We aimed to evaluate the relation between menstrual and reproductive factors, exogenous hormones, and risk of pancreatic cancer (PC).
METHODS: Eleven case-control studies within the International Pancreatic Cancer Case-control Consortium took part in the present study, including in total 2838 case and 4748 control women. Pooled estimates of odds ratios (ORs) and their 95% confidence intervals (CIs) were calculated using a 2-step logistic regression model and adjusting for relevant covariates.
RESULTS: An inverse OR was observed in women who reported having had hysterectomy (ORyesvs.no, 0.78; 95% CI, 0.67-0.91), remaining significant in postmenopausal women and never-smoking women, adjusted for potential PC confounders. A mutually adjusted model with the joint effect for hormone replacement therapy (HRT) and hysterectomy showed significant inverse associations with PC in women who reported having had hysterectomy with HRT use (OR, 0.64; 95% CI, 0.48-0.84).
CONCLUSIONS: Our large pooled analysis suggests that women who have had a hysterectomy may have reduced risk of PC. However, we cannot rule out that the reduced risk could be due to factors or indications for having had a hysterectomy. Further investigation of risk according to HRT use and reason for hysterectomy may be necessary.
Fulltext The schizophrenia genetics knowledgebase: a comprehensive update of findings from candidate gene studies

Liu C, Kanazawa T, Tian Y, Mohamed Saini S, Mancuso S, Mostaid MS, et al.

Transl Psychiatry, 2019 08 27;9(1):205.
PMID: 31455759 DOI: 10.1038/s41398-019-0532-4

Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.
Recovery of endoscopy services in the era of COVID-19: recommendations from an international Delphi consensus

Bhandari P, Subramaniam S, Bourke MJ, Alkandari A, Chiu PWY, Brown JF, et al.

Gut, 2020 11;69(11):1915-1924.
PMID: 32816921 DOI: 10.1136/gutjnl-2020-322329

The COVID-19 pandemic has had a profound impact on provision of endoscopy services globally as staff and real estate were repurposed. As we begin to recover from the pandemic, a cohesive international approach is needed, and guidance on how to resume endoscopy services safely to avoid unintended harm from diagnostic delays. The aim of these guidelines is to provide consensus recommendations that clinicians can use to facilitate the swift and safe resumption of endoscopy services. An evidence-based literature review was carried out on the various strategies used globally to manage endoscopy during the COVID-19 pandemic and control infection. A modified Delphi process involving international endoscopy experts was used to agree on the consensus statements. A threshold of 80% agreement was used to establish consensus for each statement. 27 of 30 statements achieved consensus after two rounds of voting by 34 experts. The statements were categorised as pre-endoscopy, during endoscopy and postendoscopy addressing relevant areas of practice, such as screening, personal protective equipment, appropriate environments for endoscopy and infection control precautions, particularly in areas of high disease prevalence. Recommendations for testing of patients and for healthcare workers, appropriate locations of donning and doffing areas and social distancing measures before endoscopy are unique and not dealt with by any other guidelines. This international consensus using a modified Delphi method to produce a series of best practice recommendations to aid the safe resumption of endoscopy services globally in the era of COVID-19.
The Global Spine Care Initiative: care pathway for people with spine-related concerns

Haldeman S, Johnson CD, Chou R, Nordin M, Côté P, Hurwitz EL, et al.

Eur Spine J, 2018 09;27(Suppl 6):901-914.
PMID: 30151811 DOI: 10.1007/s00586-018-5721-y

PURPOSE: The purpose of this report is to describe the development of an evidence-based care pathway that can be implemented globally.
METHODS: The Global Spine Care Initiative (GSCI) care pathway development team extracted interventions recommended for the management of spinal disorders from six GSCI articles that synthesized the available evidence from guidelines and relevant literature. Sixty-eight international and interprofessional clinicians and scientists with expertise in spine-related conditions were invited to participate. An iterative consensus process was used.
RESULTS: After three rounds of review, 46 experts from 16 countries reached consensus for the care pathway that includes five decision steps: awareness, initial triage, provider assessment, interventions (e.g., non-invasive treatment; invasive treatment; psychological and social intervention; prevention and public health; specialty care and interprofessional management), and outcomes. The care pathway can be used to guide the management of patients with any spine-related concern (e.g., back and neck pain, deformity, spinal injury, neurological conditions, pathology, spinal diseases). The pathway is simple and can be incorporated into educational tools, decision-making trees, and electronic medical records.
CONCLUSION: A care pathway for the management of individuals presenting with spine-related concerns includes evidence-based recommendations to guide health care providers in the management of common spinal disorders. The proposed pathway is person-centered and evidence-based. The acceptability and utility of this care pathway will need to be evaluated in various communities, especially in low- and middle-income countries, with different cultural background and resources. These slides can be retrieved under Electronic Supplementary Material.
The Global Spine Care Initiative: methodology, contributors, and disclosures

Johnson CD, Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, et al.

Eur Spine J, 2018 09;27(Suppl 6):786-795.
PMID: 30151808 DOI: 10.1007/s00586-018-5723-9

PURPOSE: The purpose of this report is to describe the Global Spine Care Initiative (GSCI) contributors, disclosures, and methods for reporting transparency on the development of the recommendations.
METHODS: World Spine Care convened the GSCI to develop an evidence-based, practical, and sustainable healthcare model for spinal care. The initiative aims to improve the management, prevention, and public health for spine-related disorders worldwide; thus, global representation was essential. A series of meetings established the initiative's mission and goals. Electronic surveys collected contributorship and demographic information, and experiences with spinal conditions to better understand perceptions and potential biases that were contributing to the model of care.
RESULTS: Sixty-eight clinicians and scientists participated in the deliberations and are authors of one or more of the GSCI articles. Of these experts, 57 reported providing spine care in 34 countries, (i.e., low-, middle-, and high-income countries, as well as underserved communities in high-income countries.) The majority reported personally experiencing or having a close family member with one or more spinal concerns including: spine-related trauma or injury, spinal problems that required emergency or surgical intervention, spinal pain referred from non-spine sources, spinal deformity, spinal pathology or disease, neurological problems, and/or mild, moderate, or severe back or neck pain. There were no substantial reported conflicts of interest.
CONCLUSION: The GSCI participants have broad professional experience and wide international distribution with no discipline dominating the deliberations. The GSCI believes this set of papers has the potential to inform and improve spine care globally. These slides can be retrieved under Electronic Supplementary Material.
The Global Spine Care Initiative: model of care and implementation

Johnson CD, Haldeman S, Chou R, Nordin M, Green BN, Côté P, et al.

Eur Spine J, 2018 09;27(Suppl 6):925-945.
PMID: 30151805 DOI: 10.1007/s00586-018-5720-z

PURPOSE: Spine-related disorders are a leading cause of global disability and are a burden on society and to public health. Currently, there is no comprehensive, evidence-based model of care for spine-related disorders, which includes back and neck pain, deformity, spine injury, neurological conditions, spinal diseases, and pathology, that could be applied in global health care settings. The purposes of this paper are to propose: (1) principles to transform the delivery of spine care; (2) an evidence-based model that could be applied globally; and (3) implementation suggestions.
METHODS: The Global Spine Care Initiative (GSCI) meetings and literature reviews were synthesized into a seed document and distributed to spine care experts. After three rounds of a modified Delphi process, all participants reached consensus on the final model of care and implementation steps.
RESULTS: Sixty-six experts representing 24 countries participated. The GSCI model of care has eight core principles: person-centered, people-centered, biopsychosocial, proactive, evidence-based, integrative, collaborative, and self-sustaining. The model of care includes a classification system and care pathway, levels of care, and a focus on the patient's journey. The six steps for implementation are initiation and preparation; assessment of the current situation; planning and designing solutions; implementation; assessment and evaluation of program; and sustain program and scale up.
CONCLUSION: The GSCI proposes an evidence-based, practical, sustainable, and scalable model of care representing eight core principles with a six-step implementation plan. The aim of this model is to help transform spine care globally, especially in low- and middle-income countries and underserved communities. These slides can be retrieved under Electronic Supplementary Material.
The Global Spine Care Initiative: World Spine Care executive summary on reducing spine-related disability in low- and middle-income communities

Haldeman S, Nordin M, Chou R, Côté P, Hurwitz EL, Johnson CD, et al.

Eur Spine J, 2018 09;27(Suppl 6):776-785.
PMID: 30151809 DOI: 10.1007/s00586-018-5722-x

PURPOSE: Spinal disorders, including back and neck pain, are major causes of disability, economic hardship, and morbidity, especially in underserved communities and low- and middle-income countries. Currently, there is no model of care to address this issue. This paper provides an overview of the papers from the Global Spine Care Initiative (GSCI), which was convened to develop an evidence-based, practical, and sustainable, spinal healthcare model for communities around the world with various levels of resources.
METHODS: Leading spine clinicians and scientists around the world were invited to participate. The interprofessional, international team consisted of 68 members from 24 countries, representing most disciplines that study or care for patients with spinal symptoms, including family physicians, spine surgeons, rheumatologists, chiropractors, physical therapists, epidemiologists, research methodologists, and other stakeholders.
RESULTS: Literature reviews on the burden of spinal disorders and six categories of evidence-based interventions for spinal disorders (assessment, public health, psychosocial, noninvasive, invasive, and the management of osteoporosis) were completed. In addition, participants developed a stratification system for surgical intervention, a classification system for spinal disorders, an evidence-based care pathway, and lists of resources and recommendations to implement the GSCI model of care.
CONCLUSION: The GSCI proposes an evidence-based model that is consistent with recent calls for action to reduce the global burden of spinal disorders. The model requires testing to determine feasibility. If it proves to be implementable, this model holds great promise to reduce the tremendous global burden of spinal disorders. These slides can be retrieved under Electronic Supplementary Material.
Fulltext Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients

Geier CB, Ellison M, Cruz R, Pawar S, Leiss-Piller A, Zmajkovicova K, et al.

J Clin Immunol, 2022 Nov;42(8):1748-1765.
PMID: 35947323 DOI: 10.1007/s10875-022-01312-7

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
Fulltext Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk

Ghoneim DH, Zhu J, Zheng W, Long J, Murff HJ, Ye F, et al.

Cancer Epidemiol Biomarkers Prev, 2020 Dec;29(12):2735-2739.
PMID: 32967863 DOI: 10.1158/1055-9965.EPI-20-0651

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome.
METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data.
RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex.
CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk.
IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
Fulltext Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Mocci E, Kundu P, Wheeler W, Arslan AA, Beane-Freeman LE, Bracci PM, et al.

Cancer Res, 2021 Jun 01;81(11):3134-3143.
PMID: 33574088 DOI: 10.1158/0008-5472.CAN-20-3267

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10-8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P interaction = 3.08 × 10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r 2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
Fulltext Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk

Yuan F, Hung RJ, Walsh N, Zhang H, Platz EA, Wheeler W, et al.

Cancer Res, 2020 Sep 15;80(18):4004-4013.
PMID: 32641412 DOI: 10.1158/0008-5472.CAN-20-0447

Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10-6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. SIGNIFICANCE: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links