bluuebunny/crossref_metadata_2025 huggingface dataset:
Lyophilized Human Platelets Restore Hemostasis in the Presence of the P2Y12 Inhibitors Cangrelor, Ticagrelor and Clopidogrel
Authors: Dickerson Matthew , Lee Amber , Hale Anne , Moskowitz Keith A.
Published: November 2020

• Background: P2Y12 inhibitors block platelet ADP receptors thereby reducing clotting capacity. In an emergency, these agents must be reversed or therapeutically overcome to stop bleeding. Additionally, prior to and during elective procedures these inhibitors must be withdrawn, thereby increasing thrombotic risk. Lyophilized human platelets (Thrombosomes®) are stabilized platelet derived hemostatic agents currently under Phase 2 clinical development for thrombocytopenia and have potential as antiplatelet reversal agents.

• Aims: The aim of this study was to determine if lyophilized human platelets are resistant to the antiplatelet effect of P2Y12 inhibitors and therefore restore hemostasis in the presence of P2Y12 inhibitors.

• Methods: Fresh drawn platelet rich plasma (PRP) was treated with pharmacological concentrations of P2Y12 inhibitors cangrelor or ticagrelor and confirmed to inhibit ADP-stimulated aggregation on the PAP-8E Platelet Aggregometer. Changes in hemostatic properties of the P2Y12 inhibitor treated PRP were also tested under shear force on the Total Thrombus formation Analysis System (T-TAS®). P2Y12 inhibitor treated PRP samples were dosed with lyophilized platelets and tested for return of hemostatic properties by T-TAS. NOD SCID mice were used in a tail snip model to determine hemostatic efficacy of Thrombosomes® after super pharmacological doses of clopidogrel treatment.

• Results: Fresh PRP derived platelet aggregation response to ADP was inhibited by cangrelor or ticagrelor whereas lyophilized platelets did not respond to either inhibitor. Normal thrombus formation of PRP as measured by T-TAS occurred at 19.5± 1.5 minutes (n=4) but increases to 28.0±3.0 minutes with cangrelor (n=4) or 28.0±3.0 minutes with ticagrelor (n=5) treatment. The addition of 150k/µL lyophilized platelets to P2Y12-inhibited PRP reduced time to thrombus formation to lower than PRP alone; 15.5 ±0.5 minutes in the presence of cangrelor (n=3) versus 17.5 ±1.5 minutes in the presence of ticagrelor (n=5). In the in vivo tail snip mouse model animals treated with super pharmacological dose of clopidogrel bled for 18.0±10.0 minutes (n=5) unlike those not treated that only bleed for 9.5±2.5 minutes (n=6). Lyophilized platelet treated clopidogrel animals stopped bleeding at 12.5 ±4.5 minutes (n=5) after tail snip.

• Conclusion: Lyophilized human platelets, unlike normal platelets were resistant to the antiplatelet effects of P2Y12 inhibitors. In vitro and in vivo studies reveal that lyophilized human platelets can be used to recover the anti-thrombotic effect of P2Y12 antagonists, potentially allowing continued drug compliance prior to elective procedures and as a possible treatment for emergent acute bleeding while on P2Y12 antagonist therapy.

Disclosures

Dickerson: Cellphire Inc.: Current Employment. Lee:Cellphire, Inc.: Current Employment. Hale:Cellphire: Current Employment. Moskowitz:Cellphire Inc.: Current Employment.
NCOR2 Mutations Are Associated with IMiD Resistance in Human Myeloma Cells
Authors: Mori Tomoaki , Panaroni Cristina , Onyewadume Chukwuamaka , Raje Noopur S.
Published: November 2020

The immunomodulatory drug thalidomide, and its analogs, lenalidomide, and pomalidomide (IMiDs) have significantly changed the treatment paradigm of multiple myeloma (MM). Despite this progress, IMiD resistance develops in the majority of patients resulting in the development of refractory disease. Cereblon (CRBN), a direct target, has been implicated in IMiD resistance. However, alternate mechanisms of IMiD resistance independent of CRBN remain largely unknown.

To understand and study the mechanisms responsible for the development of IMiD resistance, we created lenalidomide-resistant (Len-R) and pomalidomide-resistant (Pom-R) human myeloma MM.1s cell lines, by continuous culture in the presence of lenalidomide or pomalidomide for 3 months. Whole genome sequencing of these 2 resistant cell lines compared with parental MM.1s revealed 172 genes with exonic mutations in both Len-R and Pom-R myeloma cells. Furthermore, a protein-protein interaction (PPI) network was constructed based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The PPI network demonstrated 8 genes that scored a high degree of protein-protein interaction. Among these genes, we identified NCOR2, a corepressor that negatively regulates gene expression, as a downregulated gene in resistant cell lines.

To study this further, we created NCOR2 knock out MM.1s cell lines using CRISPR/cas9 gene modification. Our data demonstrates that depletion of NCOR2 confers IMiD resistance independent to CRBN. Interestingly, Len-R, Pom-R and NCOR2 knock out MM.1s showed increased MYC protein expression, which is essential for myeloma cell survival and proliferation. A BET inhibitor, known to disrupt the binding of BRD4 to chromatin, inhibited the proliferation of Len-R and Pom-R and NCOR2 knock out MM.1s by completely suppressing MYC expression. These results indicate that NCOR2 down regulation in IMiD resistant cells induces MYC upregulation which may in part result in IMiD resistance. Our findings reveal a novel molecular mechanism associated with IMiD resistance, independent of CRBN and suggest that NCOR2-MYC pathway may be a new target for IMiD refractory patients.

Disclosures

Raje: Celgene: Consultancy.
Defining the Super Massive Transfusion in US and Coalition Forces during Combat Operations in Afghanistan and Iraq
Authors: Schauer Steven Gremel , Fisher Andrew , Bynum James , Cap Andrew P.
Published: November 2020

Introduction: Hemorrhage is the leading cause of potentially preventable death on the battlefield. After hemorrhage control, the resuscitation with blood products is essential to restore circulating volume and prevent coagulopathy. While massive transfusion (MT) occurs frequently after major trauma, it remains unclear who the subset of casualties is that define a super massive transfusion which would require mobilization of additional resources. We seek to determine what defines a super MT as this would help allocate resources.

Methods: This is a secondary analysis of a previously described dataset from the Department of Defense Trauma Registry. In this analysis, we isolated US and Coalition casualties that received at least 1 unit of packed red cells or whole blood. To describe the super MT, we sought the top quartile of total products administered within the first 24 hours.

Results: Out of the 28222 casualties within our dataset, we identified 2204 US military and 498 Coalition that met inclusion for this analysis. The median number of total products administered within the first 24 hours was 16 with 39 total product units at the 75th percentile, which included 691 casualties. Of those in the super MT group, their median injury severity score was higher (29 versus 18, p<0.001), they were most frequently injured by explosive (84% versus 69%, p<0.001), they had a higher mean emergency department pulse (116 versus 103, p<0.001), lower mean systolic 109 versus 122, p<0.001), and higher mean international normalized ratio (1.53 versus 1.28, p<0.001). They more frequently had serious injuries to the thorax (29% versus 22%, p<0.001), abdomen (32% versus 17%, p<0.001), and extremities (85% versus 64%, p<0.001). Super MT was associated with worse survival (86% versus 92%, p<0.001).

Conclusions: In our dataset, we identified the top 25th percentile of total product administration within the first 24 hours at 39 total product units. More data is needed to define this population early in their clinical course to better mobile resources early when needed.

Disclosures

No relevant conflicts of interest to declare.
Rare Case Report of Adult T-Cell Leukemia / Lymphoma (ATLL), in the City of Macau- Rio Grande Do Norte; Brazil
Authors: Ferreira Hugo Henrique de Freitas , Silva Alessandra Suelen Jardim , Júnior Lenilton Silva DA Silva , Oliveira Gustavo Henrique de Medeiros , Araujo Maria das Graças Pereira , Soares Victor lima , Bahia Frank , Oliveira Taissa Moura , Silva Dany GKC , Sales Valéria SF , Paiva Aldair Sousa , Cavalcanti Geraldo Barroso
Published: November 2020

Introduction:Adult T-cell leukemia / lymphoma (ATLL) is a rare type of malignant haemopathy with the Human T-Cell Lymphotropic Virus type I (HTLV-1) as its etiologic agent. The clinical picture includes skin lesions, hypercalcemia, elevated lactate dehydrogenase (LDH), adenomegaly, myelopathy and leukocytosis with atypical TCD4 lymphocytes.Objective:To report a case of a patient from the city of Macau-RN, with ATLL, presenting skin lesions, weight loss (> 13%), leukocytosis and supraclavicular lymph node enlargement. Case Description: Male patient, bricklayer, 67-year-old, hypertensive, was admitted to a hospital in Natal-RN, with severe itching, diffuse exanthematic skin lesions for 13 days, adynamia, associated with progressive, weight loss (P: 73Kg, 63Kg -13.6%), hyporexia, feverish (37.8 ° C), insidious and progressive drowsiness. Physical examination showed palpable lymphadenomegaly in the right supraclavicular chain, 1 cm, mobile and painless. Painful abdomen on deep palpation in the right hypochondrium and left iliac fossa, moderate hepatosplenomegaly. The blood count showed leukocytosis with the presence of atypical lymphocytes with convoluted nucleus (Flow-Cell), Creatinine (6.81), urea 349, hyperuricemia (14.9 mg / dL), hypercalcemia (12.8), LDH (723), Alkaline phosphatase (1388) GGT (183). Abdominal, kidney and urinary tract ultrasound revealed acute pancreatitis with signs of saponification (steatonecrosis of peripancreatic fat) and bilateral acute parenchymal nephropathy, respectively. The transthoracic echocardiogram identified aortic and mitral valve sclerosis. Immunophenotyping by flow cytometry found lymphoproliferative disease of mature TCD4 + cells, and the diagnosis of ATLL was confirmed by the serological reagent for HTLV-1. From then on, adequate treatment for ATLL was started with reversion of the clinical period, currently being followed up on an outpatient basis.Conclusions:The multiprofessional performance with accurate clinical investigation associated and specific laboratory exams such as immunophenotyping by flow cytometry and serological tests are essential for the early diagnosis and treatment of ATLL, a rare entity in the state of Rio Grande do Norte., Brazil and that high mortality when not diagnosed and treated early.

Disclosures

No relevant conflicts of interest to declare.
CD200 expression marks leukemia stem cells in human AML
Authors: Ho Jenny M. , Dobson Stephanie M. , Voisin Veronique , McLeod Jessica , Kennedy James A. , Mitchell Amanda , Jin Liqing , Eppert Kolja , Bader Gary , Minden Mark D. , Dick John E. , Wang Jean C. Y.
Published: November 2020

The leukemia stem cell (LSC) populations of acute myeloid leukemia (AML) exhibit phenotypic, genetic, and functional heterogeneity that contribute to therapy failure and relapse. Progress toward understanding the mechanistic basis for therapy resistance in LSCs has been hampered by difficulties in isolating cell fractions that enrich for the entire heterogeneous population of LSCs within individual AML samples. We previously reported that CD200 gene expression is upregulated in LSC-containing AML fractions. Here, we show that CD200 is present on a greater proportion of CD45dim blasts compared with more differentiated CD45high cells in AML patient samples. In 75% (49 of 65) of AML cases we examined, CD200 was expressed on ≥10% of CD45dim blasts; of these, CD200 identified LSCs within the blast population in 9 of 10 (90%) samples tested in xenotransplantation assays. CD200+ LSCs could be isolated from CD200+ normal HSCs with the use of additional markers. Notably, CD200 expression captured both CD34– and CD34+ LSCs within individual AML samples. Analysis of highly purified CD200+ LSC-containing fractions from NPM1-mutated AMLs, which are commonly CD34–, exhibited an enrichment of primitive gene expression signatures compared with unfractionated cells. Overall, our findings support CD200 as a novel LSC marker that is able to capture the entire LSC compartment from AML patient samples, including those with NPM1 mutation.
Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma
Authors: Pasquini Marcelo C. , Hu Zhen-Huan , Curran Kevin , Laetsch Theodore , Locke Frederick , Rouce Rayne , Pulsipher Michael A. , Phillips Christine L. , Keating Amy , Frigault Matthew J. , Salzberg Dana , Jaglowski Samantha , Sasine Joshua P. , Rosenthal Joseph , Ghosh Monalisa , Landsburg Daniel , Margossian Steven , Martin Paul L. , Kamdar Manali K. , Hematti Peiman , Nikiforow Sarah , Turtle Cameron , Perales Miguel-Angel , Steinert Patricia , Horowitz Mary M. , Moskop Amy , Pacaud Lida , Yi Lan , Chawla Raghav , Bleickardt Eric , Grupp Stephan
Published: November 2020

Tisagenlecleucel is a CD19 chimeric antigen receptor (CAR) T-cell therapy approved for treatment of pediatric and young adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and adults with non-Hodgkin lymphoma (NHL). The initial experience with tisagenlecleucel in a real-world setting from a cellular therapy registry is presented here. As of January 2020, 511 patients were enrolled from 73 centers, and 410 patients had follow-up data reported (ALL, n = 255; NHL, n = 155), with a median follow-up of 13.4 and 11.9 months for ALL and NHL, respectively. Among patients with ALL, the initial complete remission (CR) rate was 85.5%. Twelve-month duration of response (DOR), event-free survival, and overall survival (OS) rates were 60.9%, 52.4%, and 77.2%, respectively. Among adults with NHL, the best overall response rate was 61.8%, including an initial CR rate of 39.5%. Six-month DOR, progression-free survival, and OS rates were 55.3%, 38.7%, and 70.7%, respectively. Grade ≥3 cytokine release syndrome and neurotoxicity were reported in 11.6% and 7.5% of all patients, respectively. Similar outcomes were observed in patients with in-specification and out-of-specification products as a result of viability <80% (range, 61% to 79%). This first report of tisagenlecleucel in the real-world setting demonstrates outcomes with similar efficacy and improved safety compared with those seen in the pivotal trials.
Household air pollution and under-five mortality in sub-Saharan Africa: an analysis of 14 demographic and health surveys
Authors: Bickton Fanuel Meckson , Ndeketa Latif , Sibande Grace Thandekire , Nkeramahame Juvenal , Payesa Chipiliro , Milanzi Edith B.
Published: November 2020

Background

Globally, over four million deaths are attributed to exposure to household air pollution (HAP) annually. Evidence of the association between exposure to HAP and under-five mortality in sub-Saharan Africa (SSA) is insufficient. We assessed the association between exposure to HAP and under-five mortality risk in 14 SSA countries.

Methods

We pooled Demographic and Health Survey (DHS) data from 14 SSA countries (N = 164376) collected between 2015 and 2018. We defined exposure to HAP as the use of biomass fuel for cooking in the household. Under-five mortality was defined as deaths before age five. Data were analyzed using mixed effects logistic regression models.

Results

Of the study population, 73% were exposed to HAP and under-five mortality was observed in 5%. HAP exposure was associated with under-five mortality, adjusted odds ratio (OR) 1.33 (95% confidence interval (CI) [1.03–1.71]). Children from households who cooked inside the home had higher risk of under-five mortality compared to households that cooked in separate buildings [0.85 (0.73–0.98)] or outside [0.75 (0.64–0.87)]. Lower risk of under-five mortality was also observed in breastfed children [0.09 (0.05-0.18)] compared to non-breastfed children.

Conclusions

HAP exposure may be associated with an increased risk of under-five mortality in sub-Saharan Africa. More carefully designed longitudinal studies are required to contribute to these findings. In addition, awareness campaigns on the effects of HAP exposure and interventions to reduce the use of biomass fuels are required in SSA.
SAlign–a structure aware method for global PPI network alignment
Authors: Ayub Umair , Haider Imran , Naveed Hammad
Published: November 2020

Background

High throughput experiments have generated a significantly large amount of protein interaction data, which is being used to study protein networks. Studying complete protein networks can reveal more insight about healthy/disease states than studying proteins in isolation. Similarly, a comparative study of protein–protein interaction (PPI) networks of different species reveals important insights which may help in disease analysis and drug design. The study of PPI network alignment can also helps in understanding the different biological systems of different species. It can also be used in transfer of knowledge across different species. Different aligners have been introduced in the last decade but developing an accurate and scalable global alignment algorithm that can ensures the biological significance alignment is still challenging.

Results

This paper presents a novel global pairwise network alignment algorithm, SAlign, which uses topological and biological information in the alignment process. The proposed algorithm incorporates sequence and structural information for computing biological scores, whereas previous algorithms only use sequence information. The alignment based on the proposed technique shows that the combined effect of structure and sequence results in significantly better pairwise alignments. We have compared SAlign with state-of-art algorithms on the basis of semantic similarity of alignment and the number of aligned nodes on multiple PPI network pairs. The results of SAlign on the network pairs which have high percentage of proteins with available structure are 3–63% semantically better than all existing techniques. Furthermore, it also aligns 5–14% more nodes of these network pairs as compared to existing aligners. The results of SAlign on other PPI network pairs are comparable or better than all existing techniques. We also introduce $$\hbox {SAlign}^{\mathrm{mc}}$$

SAlign
mc

, a Monte Carlo based alignment algorithm, that produces multiple network alignments with similar semantic similarity. This helps the user to pick biologically meaningful alignments.

Conclusion

The proposed algorithm has the ability to find the alignments that are more biologically significant/relevant as compared to the alignments of existing aligners. Furthermore, the proposed method is able to generate alternate alignments that help in studying different genes/proteins of the specie.
LncRNA IMFlnc1 promotes porcine intramuscular adipocyte adipogenesis by sponging miR-199a-5p to up-regulate CAV-1
Authors: Wang Jing , Chen Ming-yue , Chen Jun-feng , Ren Qiao-ling , Zhang Jia-qing , Cao Hai , Xing Bao-song , Pan Chuan-ying
Published: November 2020

Background

Local Chinese local pig breeds have thinner muscle fiber and higher intramuscular-fat (IMF) content. But its regulation mechanism has not been discussed in-depth. Studies indicated that long non coding RNAs (lncRNAs) play important role in muscle and fat development.

Results

The lncRNAs expressional differences in the longissimus dorsi (LD) muscle were identified between Huainan pigs (local Chinese pigs, fat-type, HN) and Large White pigs (lean-type, LW) at 38, 58, and 78 days post conception (dpc). In total, 2131 novel lncRNAs were identified in 18 samples, and 291, 305, and 683 differentially expressed lncRNAs (DELs) were found between these two breeds at three stages, respectively. The mRNAs that co-expressed with these DELs were used for GO and KEGG analysis, and the results showed that muscle development and energy metabolism were more active at 58 dpc in HN, but at 78 dpc in LW pigs. Muscle cell differentiation and myofibril assembly might associated with earlier myogenesis and primary-muscle-fiber assembly in HN, and cell proliferation, insulin, and the MAPK pathway might be contribute to longer proliferation and elevated energy metabolism in LW pigs at 78 dpc. The PI3K/Akt and cAMP pathways were associated with higher IMF deposition in HN. Intramuscular fat deposition-associated long noncoding RNA 1 (IMFlnc1) was selected for functional verification, and results indicated that it regulated the expressional level of caveolin-1 (CAV-1) by acting as competing endogenous RNA (ceRNA) to sponge miR-199a-5p.

Conclusions

Our data contributed to understanding the role of lncRNAs in porcine-muscle development and IMF deposition, and provided valuable information for improving pig-meat quality.
Genome-wide identification of the restorer-of-fertility-like (RFL) gene family in Brassica napus and expression analysis in Shaan2A cytoplasmic male sterility
Authors: Ning Luyun , Wang Hao , Li Dianrong , Li Yonghong , Chen Kang , Chao Hongbo , Li Huaixin , He Jianjie , Li Maoteng
Published: November 2020

Background

Cytoplasmic male sterility (CMS) is very important in hybrid breeding. The restorer-of-fertility (Rf) nuclear genes rescue the sterile phenotype. Most of the Rf genes encode pentatricopeptide repeat (PPR) proteins.

Results

We investigated the restorer-of-fertility-like (RFL) gene family in Brassica napus. A total of 53 BnRFL genes were identified. While most of the BnRFL genes were distributed on 10 of the 19 chromosomes, gene clusters were identified on chromosomes A9 and C8. The number of PPR motifs in the BnRFL proteins varied from 2 to 19, and the majority of BnRFL proteins harbored more than 10 PPR motifs. An interaction network analysis was performed to predict the interacting partners of RFL proteins. Tissue-specific expression and RNA-seq analyses between the restorer line KC01 and the sterile line Shaan2A indicated that BnRFL1, BnRFL5, BnRFL6, BnRFL8, BnRFL11, BnRFL13 and BnRFL42 located in gene clusters on chromosomes A9 and C8 were highly expressed in KC01.

Conclusions

In the present study, identification and gene expression analysis of RFL gene family in the CMS system were conducted, and seven BnRFL genes were identified as candidates for the restorer genes in Shaan2A CMS. Taken together, this method might provide new insight into the study of Rf genes in other CMS systems.
Comparative cellular, physiological and transcriptome analyses reveal the potential easy dehulling mechanism of rice-tartary buckwheat (Fagopyrum Tararicum)
Authors: Li Hong-You , Wu Chao-Xin , Lv Qiu-Yu , Shi Tao-Xiong , Chen Qi-Jiao , Chen Qing-Fu
Published: November 2020

Background

Tartary buckwheat has gained popularity in the food marketplace due to its abundant nutrients and high bioactive flavonoid content. However, its difficult dehulling process has severely restricted its food processing industry development. Rice-tartary buckwheat, a rare local variety, is very easily dehulled, but the cellular, physiological and molecular mechanisms responsible for this easy dehulling remains largely unclear.

Results

In this study, we integrated analyses of the comparative cellular, physiological, transcriptome, and gene coexpression network to insight into the reason that rice-tartary buckwheat is easy to dehull. Compared to normal tartary buckwheat, rice-tartary buckwheat has significantly brittler and thinner hull, and thinner cell wall in hull sclerenchyma cells. Furthermore, the cellulose, hemicellulose, and lignin contents of rice-tartary buckwheat hull were significantly lower than those in all or part of the tested normal tartary buckwheat cultivars, respectively, and the significant difference in cellulose and hemicellulose contents between rice-tartary buckwheat and normal tartary buckwheat began at 10 days after pollination (DAP). Comparative transcriptome analysis identified a total of 9250 differentially expressed genes (DEGs) between the rice- and normal-tartary buckwheat hulls at four different development stages. Weighted gene coexpression network analysis (WGCNA) of all DEGs identified a key module associated with the formation of the hull difference between rice- and normal-tartary buckwheat. In this specific module, many secondary cell wall (SCW) biosynthesis regulatory and structural genes, which involved in cellulose and hemicellulose biosynthesis, were identified as hub genes and displayed coexpression. These identified hub genes of SCW biosynthesis were significantly lower expression in rice-tartary buckwheat hull than in normal tartary buckwheat at the early hull development stages. Among them, the expression of 17 SCW biosynthesis relative-hub genes were further verified by quantitative real-time polymerase chain reaction (qRT-PCR).

Conclusions

Our results showed that the lower expression of SCW biosynthesis regulatory and structural genes in rice-tartary buckwheat hull in the early development stages contributes to its easy dehulling by reducing the content of cell wall chemical components, which further effects the cell wall thickness of hull sclerenchyma cells, and hull thickness and mechanical strength.
Association of hemoglobin glycation index and its interaction with obesity/family history of hypertension on hypertension risk: a community-based cross-sectional survey
Authors: Mi Jing , Song Jian , Zhao Yingying , Wu Xuesen
Published: November 2020

Background

Hemoglobin glycation index (HGI) is considered to be a convenient measurable indicator to assess the inter-individual variation of HbA1c. In the present study, we tested the relationship between HGI and risk of hypertension, and further explored the possible interacting influences of HGI with other such factors on hypertension risk among Chinese individuals.

Methods

The eligible subjects were chosen from a community-based cross-sectional survey in China. We collected relevant data and clinical indicators for each participant. HGI was calculated as “measured HbA1c-predicted HbA1c” and divided into four categories according to quartile. The following indicators were used to assess interactive effects: (1) relative excess risk due to interaction (RERI); (2) attributable proportion due to interaction (AP); and (3) synergy index (SI). Statistical analysis was performed using R software.

Results

Specifically, 1777 eligible participants were selected in this cross-sectional survey. There were 433 subjects who were identified to have hypertension (24.4%). A significant increase in the prevalence of hypertension from Q1 to Q4 of HGI was observed (p < 0.001). Multivariable logistic model demonstrated that subjects at the highest HGI group had a substantially increased risk of being hypertensive than subjects in the first quartile of HGI, as indicated by the OR value of 1.87 (95% CI 1.26–2.78). Moreover, a significant interaction between family history of hypertension and HGI on hypertension risk was detected (RERI: 1.36, 95% CI 0.11–2.63; AP: 0.43, 95% CI 0.17–0.69; and SI:2.68, 95% CI 1.10–6.48). The interactive effect between HGI and abdominal obesity was also found to be significant, as estimated by the value of RERI (1.04, 95% CI 0.24–1.85), AP (0.33, 95% CI 0.11–0.56) and SI (1.96, 95% CI 1.01–3.79). However, in the analysis of the interaction between HGI and general obesity, only the AP value (0.28, 95% CI 0.01–0.54) was observed to be significant.

Conclusion

High HGI was independently associated with the risk of hypertension. Moreover, HGI significantly shared interactions with obesity and family history of hypertension that influenced the risk of hypertension.
An assessment of chromosomal alterations detected by fluorescence in situ hybridisation in pancreatobiliary tract malignancy
Authors: Pu Xiaohong , Zheng Hongwei , Yang Xin , Ye Qing , Fan Zhiwen , Yang Jun , Fan Xiangshan , Zhou Xiaoping , Qiu Yudong , Huang Qin , Wu Hongyan , Chen Jun
Published: November 2020

Background

Using fluorescence in situ hybridisation (FISH) to detect any gain of chromosomes 3, 7, or 17 and loss of the 9p21 locus has been proven to be sensitive in the diagnosis of pancreatobiliary tumors. However, both genetic and environmental factors contribute to the pathogenesis of pancreatobiliary tumors. Therefore, it is unknown whether this method is suitable for Chinese patients with pancreatobiliary tumors. This study aims to compare the sensitivity, specificity, predictive values and accuracy of cytology, ERCP/MRCP and FISH based on Chinese patients with pancreatobiliary tumors,and to analyze differences between brushing-based and formalin-fixed paraffin-embedded (FFPE)-based FISH.

Methods

A total of 66 brush cytology specimens obtained during ERCP were detected by FISH and cytology test respectively to compare the sensitivity, specificity, predictive values and accuracy. Besides, FFPE-based FISH was performed on 46 corresponding paraffin sections of pancreatobiliary tumors obtained by surgical resection.

Results

Our findings demonstrate that FISH greatly improves diagnostic sensitivity and negative predictive value compared to ERCP/MRCP and cytology without much reduction in specificity and positive predictive value. However, our results also indicate that FFPE-based FISH could not effectively identify the false-negative of brushing-based FISH.

Conclusions

We believe that FISH can effectively distinguish true positive and false positive results of cytological or radiological suspicions of malignancy. However, FFPE-based FISH still does not precisely recognize the false-negative of brushing-based FISH. Both cytology-based and PPFE-based FISH had limitation in some specimens.
Granulomatous cholangitis mimicking hilar cholangiocarcinoma: a case report
Authors: Fujisaki Shigeru , Takashina Motoi , Sakurai Ken-ichi , Tomita Ryouichi , Takayama Tadatoshi
Published: November 2020

Background

Hilar biliary stricture caused by isolated fungal infections in immunocompetent patients are considered to be extremely rare and difficult to the diagnose from the outset.

Case presentation

We report a unique case of granulomatous cholangitis based on isolated biliary fungal infection manifesting as obstructive jaundice and mimicking hilar cholangiocarcinoma in an immunocompetent woman. A 67-year-old Japanese woman was referred to our hospital for obstructive jaundice. She had been followed up for hypochondroplasia by the referring physician. Her total bilirubin level was 5.4 mg/dL. Viral hepatitis screening was found to be negative, and serum IgG4 was within normal limits; however, her CA19-9 level was high. Abdominal computed tomography revealed dilatation of the intrahepatic bile ducts. Abdominal echogram detected a solid mass in the hilar bile duct. Her magnetic resonance cholangiopancreatography has also revealed an abrupt stenosis of the primary biliary confluence with upstream dilatation of the intrahepatic bile ducts. Endoscopic nasobiliary drainage was then performed to improve the obstructive jaundice. Although biliary cytology did not reveal malignant findings, the bile duct in the hilum showed severe stenosis, and hilar cholangiocarcinoma could not be completely excluded. The patient had a developmental disorder based on chondrodystrophy. To avoid excessive surgical stress, such as hepatic lobectomy, we performed resection of the extrahepatic bile duct and Roux-en-Y hepaticojejunostomy reconstruction. Intraoperative frozen sections of the resection margins were determined to be negative for tumor. The resected specimen showed multiple strictures inside the common bile duct, numerous calculi in the lumen, and little free space. The final pathological diagnosis was granulomatous cholangitis due to fungal infection. The patient’s postoperative course was deemed uneventful. She was discharged from our hospital 23 days after surgery without antifungal treatment.

Conclusions

For a unique case of granulomatous cholangitis based on isolated biliary fungal infection mimicking hilar cholangiocarcinoma, we were able to avoid excessive invasion and performed appropriate surgical management.
Validity and reliability testing of the Spanish version of the BESTest and mini-BESTest in healthy community-dwelling elderly
Authors: Dominguez-Olivan Pilar , Gasch-Gallen Angel , Aguas-Garcia Esmeralda , Bengoetxea Ana
Published: November 2020

Background

The Balance Evaluation Systems Test (BESTest) and its abbreviated version, the Mini-BESTest are clinical examination of balance impairment, but its psychometric properties have not yet been tested in European Spanish. We aimed to assess the psychometric properties of BESTest and Mini-BESTest in Spanish in community-dwelling elderly people.

Methods

We designed a cross-sectional transcultural adaptation and validation study.

Convenience sample of thirty (N-30) adults aged 65 to 89 years old without balance problems were recruited. Two physiotherapists assessed participants at the same time. Internal consistency of Spanish BESTest and Mini-BESTest was carried out by obtaining the Cronbach Alpha. The reproducibility between raters was studied with the Intraclass Correlation Coefficient. The Pearson correlation coefficient was calculated by comparing the relationship between the BESTest, mini-BESTest, Berg Balance Scale (BBS) and Falls Efficacy Scale-International (FES-I).

Results

BESTest and Mini-BESTest showed good internal consistency. BESTest and Mini-BESTest total scores showed an excellent inter-rater agreement. There was a significant correlation between total score of the BESTest and the Mini-BESTest (r = 0.65; p < 0.001). BESTest had a moderate association with BBS and a strong association with FES-I. Mini-BESTest had a fair correlation with BBS and FES-I. Total scores obtained by women at BESTest and at Mini-BESTest were significantly lower than those reached by men. The differences observed in all the test when disaggregating data by sex require further research.

Conclusions

Spanish versions of BESTest and Mini-BESTest are comprehensible for new raters. They are reliable tools to provide information on which particular balance systems show impairment in community dwelling older adults. Elderly women had a worse quality of balance and a greater perception of their risk of falling.

Trial registration

This study was registered in ClinicalTrials.gov with NCT 03403218 on 2018/01/17.
The use of intravenous iron in pregnancy: for whom and when? A survey of Australian and New Zealand obstetricians
Authors: Smith-Wade Sarah , Kidson-Gerber Giselle , Shand Antonia , Grzeskowiak Luke , Henry Amanda
Published: November 2020

Background

Iron deficiency anaemia in pregnancy (IDAP) affects 11–18% of Australian pregnancies and is associated with adverse perinatal outcomes. National prescribing data suggests the use of intravenous iron in pregnancy is increasingly common. This study aimed to: 1) Establish the current patterns of intravenous iron use by Fellows of the Royal Australian and New Zealand College of Obstetricians (FRANZCOG) when treating iron deficiency and IDAP including immediately postpartum and; 2) Assess FRANZCOG opinions regarding potential trial of intravenous iron for first-line treatment of IDAP.

Methods

An online survey of RANZCOG Fellows practicing obstetrics was distributed in September 2018. Results were analysed descriptively and responses compared by clinician demographics using Chi-squared testing.

Results

Of 484 respondents (21% of FRANZCOG), 457 were currently practicing obstetrics. Most prescribed intravenous iron in pregnancy (96%) and/or postpartum (85%). Most intravenous iron was prescribed for IDAP (98%) rather than iron deficiency without anaemia (53%), and for IDAP most commonly second-line to failed oral iron supplementation and first-line in special circumstances (59%). Intravenous iron prescribing was associated with shorter time since FRANZCOG completion (p = 0.01), public hospital practice (p = 0.008) and higher hospital birth numbers (p = 0.01). Most respondents (90%) would consider a randomised controlled trial of first-line intravenous iron for IDAP, although views on appropriate thresholds differed.

Conclusions

Almost all respondents prescribed intravenous iron for IDAP, and while mostly used for second-line treatment over half sometimes used it first-line. With accelerating intravenous iron use, further research is required into its optimal use in pregnancy, recognizing important clinical outcomes and cost effectiveness.
Postnatal care education in health facilities in Accra, Ghana: perspectives of mothers and providers
Authors: Owen Medge D. , Colburn Elizabeth , Tetteh Cecilia , Srofenyoh Emmanuel K.
Published: November 2020

Background

The recent use of antenatal care (ANC) has steadily improved in low- and middle-income countries (LMIC), but postnatal care (PNC) has been widely underutilized. Most maternal and newborn deaths occur during the critical postnatal period, but PNC does not receive adequate attention or support, particularly in Sub-Saharan Africa. In Ghana, the majority of mothers attend four ANC assessments, but far fewer receive the four recommended PNC visits. This study sought to understand perceptions toward PNC counselling administered prior to discharge among both mothers and healthcare providers in the Greater Accra Region of Ghana.

Methods

Facility assessments were conducted among 13 health facilities to determine the number and type of deliveries, staffing, timing of discharge following delivery and the PNC schedule. Structured interviews were conducted for 172 mothers over four-months in facilities, which included one regional hospital, four district hospitals, and eight sub-district level hospitals. Additionally, healthcare providers from 12 of the 13 facilities were interviewed. Data were analyzed with Chi-square or students t-test, as appropriate, with p < 0.05 considered statistically significant.

Results

Ninety-nine percent of mothers received PNC instructions prior to hospital discharge, the majority of which were given in a group format. Mothers in the regional hospital were significantly more likely to have been informed about maternal danger signs but were less likely to know the PNC schedule than were mothers in district and sub-district facilities. No mother recalled more than four maternal or five newborn danger signs. Thirty-eight percent of facilities did not have PNC guidelines. Most patient and providers reported positive attitudes toward the level of PNC education, however, knowledge was inconsistent regarding the number and timing of PNC visits as well as other critical information. Only 23% of patients reported having a contact number to call for concerns.

Conclusions

Despite overall positive feelings toward PNC among Ghanaian mothers and providers, there are significant gaps in PNC education that must be addressed in order to recognize problems and to prevent serious complications. Improvements in pre-discharge PNC counseling should be provided in Ghana to give mothers and babies a better chance at survival in the critical postnatal period.
Easy and effective test to evaluate tear-film stability for self-diagnosis of dry eye syndrome: blinking tolerance time (BTT)
Authors: Hwang Hyung Bin , Ku Yong Ho , Kim Eun Chul , Kim Hyun Seung , Kim Man Soo , Hwang Ho Sik
Published: November 2020

Background

The tear film breakup time (tBUT) is a clinical evaluation of evaporative dry eye disease assessed by instilling topical fluorescein into the eyes. In the present study, we introduce a new diagnostic test, blinking tolerance time (BTT), for self-evaluation of tear-film stability. We compared the results with the tBUT and validated the BTT test for self-assessment of tear film instability.

Methods

This was a prospective controlled study involving 212 eyes of 106 participants 20–79 years of age. A total of 114 eyes of 57 dry eye patients and 98 eyes of 49 healthy subjects were included in the study. All patients and subjects were administered the following tests to diagnose dry eye disease: Ocular Surface Disease Index, BTT, tBUT, slit-lamp examination, corneal stain score, and Schirmer I test (without anesthesia). Patients and subjects were instructed not to blink for as long possible after reset blinking. The time interval between the reset blink and the next blink was measured. The mean of 3 tBUT values in both the right and left eyes was defined as tBUTBE. Correlations between the BTT and tBUTBE were also evaluated. To evaluate the diagnostic efficacy of the BTT and tBUT tests, receiver operating characteristic (ROC) curves were generated to obtain a cutoff score, and the sensitivities of the tests against the specificity at all possible thresholds were plotted.

Results

Spearman’s correlation analysis revealed a significant weakly positive correlation between BTT and tBUTBE (r = 0.447; p = 0.000). The intraclass correlation coefficient (ICC) of the tBUT was 0.679 (95% confidence interval [CI]: 0.575–0.765) and the ICC of the BTT was 0.904 (95% CI: 0.867–0.932). The area under the ROC curve did not significantly differ between the tBUTBE (0.678) and BTT (0.628, p = 0.641). When the cutoff value of the BTT test was set to 8.1 s, the sensitivity was 63.3% and the specificity was 56.1%.

Conclusion

The BTT test is a simple, inexpensive, and effective method for self-diagnosing dry eye that can also be used in the clinical setting.
Etiology of intellectual disability in individuals from special education schools in the south of Brazil
Authors: Oliveira Luan Freitas , Chaves Tiago Fernando , Baretto Nathacha , de Luca Gisele Rozone , Barbato Ingrid Tremel , Barbato Filho Jorge Humberto , Ocampos Maristela , Maris Angelica Francesca
Published: November 2020

Background

Intellectual Disability (ID) is characterized by significant limitations that affect intellectual functioning, adaptive behavior, and practical skills which directly interfere with interpersonal relationships and the environment. In Western countries, individuals with ID are overrepresented in the health system, often due to associated comorbidities, and its life-time cost places ID as one of the most expensive conditions of all diagnoses in the International Classification of Diseases. Most of the people affected (75%) live in low-income countries, suffer from malnutrition, lack health care, and do not have access to adequate treatment. The aim of this study was to obtain an estimate of the diagnostic status as well as the prevalence of familial ID among individuals with serious (moderate or severe) ID in a region of the State of Santa Catarina, investigating attendees of special education schools of the Florianópolis Macroregion.

Methods

This was a cross-sectional study conducted between August 2011 and August 2014, through a semi-structured screening questionnaire for the collection of relevant developmental, clinical, familial and educational data, applied in an interview to guardians of students of special education schools of the macroregion of Florianópolis.

Results

The participant special schools enrolled close to 1700 students during the study period and the questionnaire was applied to 849 (50.5%). The male to female ratio of the participants was 1.39:1. Clear etiologic explanations were relatively scarce (24%); most diagnoses referring only to the type and the degree of impairment and for the majority (61.4%) the cause was unknown. About half were sporadic cases within their families (considering three generations). For 44.2% at least one other case of an ID-related condition in the extended family was mentioned, with 293 (34.5%) representing potential familial cases.

Conclusion

Here we describe the epidemiological profile, the available diagnostics, etiology, family history and possible parental consanguinity of participants with ID of special education schools in the South of Brazil. The main results show the need for etiological diagnosis and uncover the relevance of potential hereditary cases in a population where consanguineous unions have a relatively low frequency (0,6%) and highlight the need for public health actions.
Increasing trends in incidence of preterm birth among 2.5 million newborns in Guangzhou, China, 2001 to 2016: an age-period-cohort analysis
Authors: Lu Jinhua , Wei Dongmei , Shen Songying , Xia Xiaoyan , He Jianrong , Sun Yan , Lam Kin Bong Hubert , Bao Wei , Xia Huimin , Qiu Xiu
Published: November 2020

Background

The incidence of preterm birth (PTB, < 37 weeks of gestation) has been increasing in China and many other countries in recent years. However, the causes of the increase were not well understood. The current study aims to examine the contribution of maternal age, period of delivery, and maternal birth cohorts to long-term trends in preterm birth in Guangzhou, China.

Methods

In a retrospective population-based study, data were obtained from 2,535,000 singleton live births with 20–43 gestational weeks from 2001 to 2016 and recorded in the Guangzhou Perinatal Health Care and Delivery Surveillance System, in China. The age-period-cohort models were applied to investigate the temporal changes in incidences of PTB, stratified by parity.

Results

The incidence of preterm birth steadily increased from 5.1% in 2001 to 5.9% in 2016, with larger rise in primiparous mothers (from 5.0 to 5.9%) compared to multiparous mothers (from 5.6 to 5.9%). A J-shaped and a V-shaped relationship were found between maternal age and PTB among primiparous and multiparous mothers, respectively. A linear cohort effect was found among primiparous mothers with the lowest risk of PTB [risk ratio (RR) = 0.81, 95% confidence interval (CI): 0.74 to 0.89] in 1961 and the highest risk (RR = 1.06, 95% CI: 1.00 to 1.13) in 1997 compared to the mothers born in 1981. An inverse U-shaped association between maternal birth cohort and PTB was found in multiparous mothers. There were weak decreasing period effects on the trend of overall PTB among multiparous mothers and on the trend of extremely (< 27 weeks) or very (28–31 weeks) PTB among both parity groups during the period of 2001–2012.

Conclusions

Our findings showed the PTB incidences had been increasing in the past 16 years in Guangzhou, China and both maternal age and cohort effects contributed to these trends. Further studies are recommended on the impact of altered maternal age and parity on premature births and corresponding public education and public health policies.