bluuebunny/crossref_metadata_2025 huggingface dataset:
HEMOGRAMS AND MYELOGRAMS OF HEALTHY FEMALE MICE OF C-57 BROWN AND CFW STRAINS
Authors: ENDICOTT K. M. , GUMP HAZEL
Published: November 2019

The hemogram and myelogram of healthy female mice 2 months old of two strains, C-57 brown and CFW albino, are presented. The average cellularity of marrow has been determined and the marrow differential has been corrected with this figure to establish a normal index of the total quantity of each type of cell. The average weight of the body and of the submaxillary lymph nodes, thymus, spleen, and kidney are presented.
A METHOD FOR THE SEPARATION OF LEUKOCYTES FROM WHOLE BLOOD BY FLOTATION ON SERUM ALBUMIN
Authors: VALLEE BERT L. , HUGHES WALTER L. , GIBSON JOHN G.
Published: November 2019

A technic for the separation of leukocytes from whole blood, utilizing the known difference in density of leukocytes and erythrocytes, is described. Complete separation is effected by means of solutions of serum albumin adjusted to the correct physicochemical properties.
THE PREPARATION OF MORPHOLOGICALLY INTACT LEUKOCYTES FROM PERIPHERAL BLOOD BY MEANS OF GRAMICIDIN AND LYSOLECITHIN
Authors: SINGER THOMAS P. , SILBERBACH INGELORE , SCHWARTZ SAMUEL
Published: November 2019

A method involving the combined use of gramicidin and lysolecithin is described for the rapid and apparently quantitative isolation of morphologically intact leukocytes from circulating blood. The mixture of these two compounds gives rapid and complete lysis of erythrocytes. The use of either gramicidin or of lysolecithin alone in sufficient amount to completely lyse the red cells results in morphological damage to the leukocytes. For some as yet unknown reason, however, the combined use of these two agents in a definite ratio results in cancellation of this leukocyte damaging effect. The cells thus prepared appear to be consistently more intact morphologically than any yet prepared in this laboratory.
Phosphorylated HSP27 associates with the activation-dependent cytoskeleton in human platelets
Authors: Zhu Y , O'Neill S , Saklatvala J , Tassi L , Mendelsohn ME
Published: November 2019

The three prominently phosphorylated 29-kD proteins in thrombin- activated human platelets are forms of the mammalian 27-kD heat-shock protein (HSP27). Though the function of HSP27 is not yet known, its phosphorylation is highly correlated with platelet secretion, and recent evidence in nonhematopoietic cells suggests that HSP27 regulates cortical actin filament assembly. Therefore, the subcellular location and phosphorylation state of HSP27 in resting and thrombin-activated platelets was studied. Platelets were fractionated by established Triton X-100 lysis methods followed by differential centrifugation to obtain the 14,000g fraction (low-speed cytoskeleton), 100,000g fraction (membrane skeleton), and the 100,000g supernatant fraction containing soluble cytosolic proteins. In resting platelets, HSP27 was present principally in the 100,000g supernatant fraction. Platelet activation with thrombin led to translocation of the majority of HSP27 to the low- speed cytoskeleton. This association was reversible by DNase, supporting the idea that HSP27 is a specific component of the actin cytoskeleton. Immunofluorescence studies similarly showed HSP27 is cytoplasmic in resting platelets but colocalizes with actin in fully spread, glass-activated platelets. Immunoprecipitation studies showed a small amount of constitutively phosphorylated HSP27 in resting platelets, but phosphorylation of the majority of HSP27 after thrombin activation. After activation, virtually all phosphorylated HSP27 was found in the low-speed cytoskeletal fraction, and each of the three phosphorylated forms of HSP27 were present by two-dimensional autoradiography. Furthermore, in time-course studies, the phosphorylation of HSP27 occurred just before localization of HSP27 to the low-speed pellet. These results show that, after platelet activation, HSP27 is first phosphorylated and then translocated from the cytoplasm to the assembling cytoskeleton, and suggest that HSP27 phosphorylation may be important to the binding of HSP27 to cytoskeletal components and the cytoskeletal rearrangements characteristic of platelet activation.
Monoclonal antibodies directed against the Epstein-Barr virus-encoded nuclear antigen 1 (EBNA1): immunohistologic detection of EBNA1 in the malignant cells of Hodgkin's disease
Authors: Grasser FA , Murray PG , Kremmer E , Klein K , Remberger K , Feiden W , Reynolds G , Niedobitek G , Young LS , Mueller-Lantzsch N
Published: November 2019

Monoclonal antibodies directed against the Epstein-Barr virus nuclear protein 1 (EBNA1) were used to examine conventional paraffin sections from a series of EBV-associated lymphoproliferative disorders by immunohistochemistry. The presence of latent EBV infection in tumor cells was determined by in situ hybridization for the Epstein-Barr virus early RNAs (EBERs). Of those EBER-positive cases a total of 28 of 40 cases of Hodgkin's disease, 3 of 3 cases of Burkitt's lymphoma, and 8 of 8 cases of human immunodeficiency virus-associated cerebral B-cell lymphoma expressed detectable amounts of EBNA1. In the positive cases, expression was confined to the tumor cells. No reactivity was detected in EBV-negative cases of the above tumors or in 8 cases of EBV-negative cases of large cell anaplastic non-Hodgkin lymphoma. This report provides the first unequivocal evidence for the expression of the EBNA1 protein in the tumor cells of Hodgkin's disease and validates an important reagent with which to analyze the role of EBV in various virus-associated malignancies.
One hundred twenty-five adult patients with primary acute leukemia autografted with marrow purged by mafosfamide: a 10-year single institution experience
Authors: Laporte JP , Douay L , Lopez M , Labopin M , Jouet JP , Lesage S , Stachowiak J , Fouillard L , Isnard F , Noel-Walter MP
Published: November 2019

A total of 125 acute leukemia adult patients were autografted with bone marrow (BM) purged by mafosfamide (ASTA Z) during the period of January 1983 to January 1993. The median follow-up period was 64 months (range, 3 to 126). There were 84 acute myeloblastic leukemias (AMLs) and 41 acute lymphoblastic leukemias (ALLs). At time of autologous BM transplantation (ABMT); 64 AMLs were in first complete remission (CR1), and 20 were in second CR (CR2); 35 ALL were in CR1, and 6 were in CR2. The median age of the patients was 33 years (range, 16 to 55). The median interval between achieving CR and autografting was 5 months (range, 1.3 to 23). The pretransplant regimen consisted of cyclophosphamide (120 mg/kg) and total body irradiation. All patients were grafted with autologous BM treated in vitro with mafosfamide used at levels individually adjusted in 95 patients and at a standard dose in 30 patients. The initial richness in granulomacrophagic progenitors (CFU-GM) of the harvested BMs was 5.16 x 10(4) CFU-GM/kg (range, 0.55 to 33). After mafosfamide purging, the residual CFU-GM number was 0.021 x 10(4)/kg (range, 0 to 1.78). The probability of successful engraftment was significantly higher and the time to engraftment was significantly shorter in ALL. Of 33 patients grafted with BM containing no residual CFU-GM, those with AML (n = 22) had platelet recoveries that were significantly longer than those for AML patients receiving BM with residual CFU-GM. At 8 years, patients autografted in CR1 for AML and ALL had a leukemia-free survival (LFS) of 58% and 56%, respectively, with a relapse incidence (RI) of 25% and 37%, respectively. Patients autografted in CR2 for AML had an LFS of 34% and an RI of 48% at 5 years. The incidence of late relapses was significantly higher in ALLs. By multivariate analysis, four factors were found to influence favorably engraftment in addition to a diagnosis of ALL, a younger age, ABMT performed in CR1, the adjusted dose technique of purging, and a shorter interval from CR to ABMT. Two factors were correlated with a better outcome. (1) The LFS was significantly higher and the transplant-related mortality significantly lower in patients who received richer BM. (2) The RI was significantly lower in patients autografted within 150 days from CR. Our results reinforce the view that ABMT is one approach to improve the outcome of adult patients with acute leukemia.(ABSTRACT TRUNCATED AT 250 WORDS)
Successful engraftment of T-cell-depleted haploidentical "three-loci" incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum
Authors: Aversa F , Tabilio A , Terenzi A , Velardi A , Falzetti F , Giannoni C , Iacucci R , Zei T , Martelli MP , Gambelunghe C
Published: November 2019

Patients who undergo transplantation with haploidentical “three-loci” mismatched T-cell-depleted bone marrow (BM) are at high risk for graft failure. To overcome the host-versus-graft barrier, we increased the size of the graft inoculum, which has been shown to be a major factor in controlling both immune rejection and stem cell competition in murine models. Seventeen patients (mean age, 23.2 years; range, 6 to 51 years) with end-stage chemoresistant leukemia were received transplants of a combination of BM with recombinant human granulocyte colony- stimulating factor-mobilized peripheral blood progenitor cells from HLA- haploidentical “three-loci” incompatible family members. The average concentration of colony-forming unit-granulocyte-macrophage in the final inoculum was sevenfold to 10-fold greater than that found in BM alone. The sole graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion of the graft by the soybean agglutination and E- rosetting technique. The conditioning regimen included total body irradiation in a single fraction at a fast dose rate, antithymocyte globulin, cyclophosphamide and thiotepa to provide both immunosuppression and myeloablation. One patient rejected the graft and the other 16 had early and sustained full donor-type engraftment. One patient who received a much greater quantity of T lymphocytes than any other patient died from grade IV acute GVHD. There were no other cases of GVHD > or = grade II. Nine patients died from transplant-related toxicity, 2 relapsed, and 6 patients are alive and event-free at a median follow-up of 230 days (range, 100 to 485 days). Our results show that a highly immunosuppressive and myeloablative conditioning followed by transplantation of a large number of stem cells depleted of T lymphocytes by soybean agglutination and E-rosetting technique has made transplantation of three HLA-antigen disparate grafts possible, with only rare cases of GVHD.
Acute promyelocytic leukemia cases with nonreciprocal PML/RARa or RARa/PML fusion genes
Authors: Lafage-Pochitaloff M , Alcalay M , Brunel V , Longo L , Sainty D , Simonetti J , Birg F , Pelicci PG
Published: November 2019

Tumor-associated chromosome translocations usually lead to the formation of two reciprocal fusion genes: one thought to be involved in the transformation process, the other the mechanical consequence of the translocation event. In the case of acute promyelocytic leukemia (APL) blasts, the 15;17 chromosome translocation generates the putatively transforming PML/RARa fusion gene and its reciprocal RARa/PML. We report APL cases with submicroscopic 15;17 recombinations leading to the formation of nonreciprocal PML/RARa or RARa/PML fusion genes. Therefore, each of the two reciprocal translocation products may be independently formed and selected by the leukemic phenotype, implying that both are involved in tumorigenesis.
Induction of phagocytosis by a protein tyrosine kinase
Authors: Indik ZK , Park JG , Pan XQ , Schreiber AD
Published: November 2019

The transmission of extracellular signals to cellular targets by many noncatalytic surface receptors is dependent on interaction between cytoplasmic protein tyrosine kinases (PTKs) and tyrosine-containing sequences in the cytoplasmic domain of the receptor or an associated subunit. Isoforms of each of the three classes of the noncatalytic Fc gamma receptors, Fc gamma RI, Fc gamma RII, and Fc gamma RIII, are able to transmit a phagocytic signal in transfected COS-1 cells. Both Fc gamma RI and Fc gamma RIIIA require the gamma subunit for this signaling event. The protein tyrosine kinase Syk dramatically enhances phagocytosis mediated by both these receptors and increases the number of cells able to mediate phagocytosis. Two gamma chain cytoplasmic YXXL sequences are required for this effect. The action of Syk is less pronounced on the phagocytic Fc gamma RII receptor, Fc gamma RIIA, which does not require the gamma chain for phagocytosis. However, Syk allows phagocytosis by the nonphagocytic Fc gamma RII receptor Fc gamma RIIB2, which contains only a single YXXL sequence, when an additional tyrosine-containing sequence, YMTL, is introduced. These studies indicate that the efficiency of phagocytosis is markedly enhanced by the presence of a specific protein tyrosine kinase.
Paroxysmal nocturnal hemoglobinuria clone in bone marrow of patients with pancytopenia
Authors: Nakakuma H , Nagakura S , Iwamoto N , Kawaguchi T , Hidaka M , Horikawa K , Kagimoto T , Shido T , Takatsuki K
Published: November 2019

The lack of glycosylphosphatidylinositol (GPI)-anchored membrane proteins such as decay-accelerating factor (DAF) and CD59 on blood cells has a diagnostic value in paroxysmal nocturnal hemoglobinuria (PNH). Because PNH often develops in patients with aplastic anemia (AA), we attempted to detect a PNH clone in the bone marrow (BM) of patients with AA and pancytopenia before affected cells were evident in the peripheral blood (PB). We used flow cytometry with monoclonal antibodies against DAF and CD59 for the detection of the clone. Affected cells were observed in the BM of 3 of 7 patients with AA and 1 of 3 patients with pancytopenia of unknown origin, but not in their PB. All 8 patients with apparent PNH had affected cells in their BM and PB. On the basis of the early appearance of the PNH clone in the BM, a prospective 4-month follow-up study of the PB cells was performed. The study showed the release of affected mature cells first in granulocytes, then in monocytes, and finally in lymphocytes. Ham's test was positive before affected erythrocytes were detected by flow cytometry. Our findings indicate that detection of the PNH clone in BM could be predictive of the development of PNH in patients with AA and pancytopenia.
New glucose-6-phosphate dehydrogenase mutations associated with chronic anemia
Authors: Mason PJ , Sonati MF , MacDonald D , Lanza C , Busutil D , Town M , Corcoran CM , Kaeda JS , Stevens DJ , al-Ismail S
Published: November 2019

We have identified the glucose-6-phosphate dehydrogenase mutations responsible for enzyme deficiency in nine individuals with chronic nonspherocytic hemolytic anemia. We found the variants Tokyo, Iowa, Shinshu, and Guadalajara in British subjects and Kobe in an Italian. In addition we have determined the variant Corum has the mutation 820 G-->A and have found in British subjects the mis-sense mutations 224 T-->C, 488 G-->A and 833 C-->T which have not been described before. Some, but not all, of the mutations involve amino acids located near putative substrate binding sites.
High-dose etoposide, cyclophosphamide, and total body irradiation with allogeneic bone marrow transplantation for patients with acute myeloid leukemia in untreated first relapse: a study by the North American Marrow Transplant Group
Authors: Brown RA , Wolff SN , Fay JW , Pineiro L , Collins RH Jr , Lynch JP , Stevens D , Greer J , Herzig RH , Herzig GP
Published: November 2019

Relapse is a major cause of treatment failure following allogeneic bone marrow transplantation (BMT) for acute myeloid leukemia (AML). To reduce the risk of relapse following BMT for patients with hematologic malignancy, our group developed a novel preparative regimen which combines high-dose etoposide with cyclophosphamide and total body irradiation (VPCyTBI). We now report the outcome of therapy with VPCyTBI followed by allogeneic BMT for 40 patients with AML in untreated first relapse. With the exception of increased stomatitis, the toxicity of this regimen was similar to that reported by others for CyTBI. Forty-four months after transplant the actuarial probabilities of disease-free survival (DFS), persistent or recurrent leukemia, and transplant related mortality were .29, .44, and .47 respectively. DFS was improved (P < .01) and risk of persistent or recurrent leukemia reduced (P = .005) among patients with significant (grade > or = 2) acute GVHD. Patients with 30% or more blasts on pre-BMT bone marrow examination were not at increased risk for persistent or recurrent leukemia. We conclude that VPCyTBI with allogeneic BMT is effective therapy for AML in untreated first relapse and that a randomized trial comparing this regimen with CyTBI is warranted.
Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus
Authors: Morii E , Tsujimura T , Jippo T , Hashimoto K , Takebayashi K , Tsujino K , Nomura S , Yamamoto M , Kitamura Y
Published: November 2019

The mi locus of mice encodes a member of the basic-helix-loop-helix-leucine zipper (bHLH-Zip) protein family of transcription factors (hereafter called MITF). Because the expression of the mouse mast cell protease 6 (MMCP-6) gene is remarkably reduced in mast cells of mi/mi mutant mice, we investigated the effect of MITF on the transcription of the MMCP-6 gene. First, we introduced the normal (+) MITF cDNA into mi/mi cultured mast cells using the retroviral vector. Overexpression of +-MITF but not mi-MITF normalized the expression of the MMCP-6 gene, indicating the involvement of +-MITF in the MMCP-6 gene transactivation. Second, we analyzed the promoter of the MMCP-6 gene by the transient cotransfection assay. The luciferase construct under the control of the MMCP-6 promoter and the cDNA encoding +-MITF or mi-MITF were cotransfected into NIH/ 3T3 fibroblasts. The coexpression of +- MITF but not mi-MITF increased the luciferase activity 10-fold. We found a CACATG and a CATCTG motif in the MMCP-6 promoter, both of which are generally recognized by bHLH-Zip-type transcription factors. We also found a GACCTG motif that was strongly bound by +-MITF. These three motifs were necessary for the 10-fold transactivation ability of the MMCP-6 promoter by +-MITF. Mutations of each motif significantly reduced the transactivation, suggesting that +-MITF directly transactivated the MMCP-6 gene through these three motifs.
The erythropoietin gene is expressed strongly in the mammalian mesonephric kidney
Authors: Wintour EM , Butkus A , Earnest L , Pompolo S
Published: November 2019

In the ovine fetus at 41 days of gestation (term is 150 days), there are two sets of kidneys, mesonephrol and metanephrol. We have examined the expression of the erythropoietin (Epo) gene in both types of kidneys by competitive reverse transcriptase-polymerase chain reaction and hybridization histochemistry and compared the expression to that of the 60-day fetal metanephros. At 41 days, the Epo gene was expressed in both mesonephros and metanephros, as well as in the fetal liver. The cells expressing the Epo gene in the mesonephros were interstitial cells in the vicinity of the proximal tubules.
Pyrrolidine dithiocarbamate inhibits the production of interleukin-6, interleukin-8, and granulocyte-macrophage colony-stimulating factor by human endothelial cells in response to inflammatory mediators: modulation of NF-kappa B and AP-1 transcription factors activity
Authors: Munoz C , Pascual-Salcedo D , Castellanos MC , Alfranca A , Aragones J , Vara A , Redondo MJ , de Landazuri MO
Published: November 2019

Endothelial cells (EC) play a key role in the inflammatory response, both by the production of proinflammatory cytokines and by their interaction with leukocytes. Molecular genetic analysis has demonstrated that functional NF-kappa B sites are involved in the transcription of interleukin-6 (IL-6), IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) genes in response to inflammatory mediators. Thus, we have explored the effect of two inhibitors of the NF-kappa B activation, pyrrolidine dithiocarbamate (PDTC) and N-acetylcysteine (NAC), on the production of these cytokines by EC. Both PDTC and NAC inhibited, in a dose-dependent manner, the synthesis of IL-6, IL-8, and GM-CSF induced by tumor necrosis factor (TNF)-alpha or bacterial lipopolysaccharides (LPS) in human umbilical vein endothelial cells (HUVEC). PDTC appeared to prevent IL-6, IL-8, and GM-CSF gene transcription, as it blocked the induction of specific mRNA by TNF-alpha or LPS. The TNF-alpha mediated transcriptional activation of a chloramphenicol acetyltransferase (CAT) plasmid containing three copies of the -72 kappa B binding site from the IL-6 promoter was abrogated by PDTC. According to transfection experiments, electrophoretic mobility shift assays (EMSA) demonstrated that the antioxidant prevented the induction of NF-kappa B DNA-binding activity by TNF-alpha. Under the same conditions, PDTC by itself or in combination with TNF-alpha, enhanced the DNA-binding activity of AP-1, as well as c-fos and c-jun mRNA levels. Altogether, these results indicate that the antioxidant PDTC specifically inhibits the transcription of IL-6, IL-8, and GM-CSF genes through the inhibition of the NF-kappa B activation, while increasing the expression of AP-1. Our data make evident the antiinflammatory and immunoregulatory potential of the pharmacological inhibition of the NF-kappa B activation. In addition, PDTC and related molecules may be a useful tool to explore the expression of genes involved in the inflammatory response.
Airway G-CSF identifies neutrophilic inflammation and contributes to asthma progression
Authors: Kim Young-Min , Kim Hyekang , Lee Seungwon , Kim Sora , Lee Jong-Uk , Choi Youngwoo , Park Han Wook , You Gihoon , Kang Hansol , Lee Seyoung , Park Jong-Sook , Park Yunji , Park Hae-Sim , Park Choon-Sik , Lee Seung-Woo
Published: November 2019

Stratification of asthmatic patients based on relevant biomarkers enables the prediction of responsiveness against immune-targeted therapies in patients with asthma. Individualised therapy in patients with eosinophilic asthma has yielded improved clinical outcomes; similar approaches in patients with neutrophilic asthma have yet to be developed. We determined whether colony-stimulating factors (CSFs) in the airway reflect the inflammatory phenotypes of asthma and contribute to disease progression of neutrophilic asthma.

We analysed three different mouse models of asthma and assessed cytokine profiles in sputum from human patients with asthma stratified according to inflammatory phenotype. In addition, we evaluated the therapeutic efficacy of various cytokine blockades in a mouse model of neutrophilic asthma.

Among the CSFs, airway granulocyte CSF (G-CSF) contributes to airway neutrophilia by promoting neutrophil development in bone marrow and thereby distinguishes neutrophilic inflammation from eosinophilic inflammation in mouse models of asthma. G-CSF is produced by concurrent stimulation of the lung epithelium with interleukin (IL)-17A and tumour necrosis factor (TNF)-α; therefore, dual blockade of upstream stimuli using monoclonal antibodies or genetic deficiency of the cytokines in IL-17A×TNF-α double-knockout mice reduced the serum level of G-CSF, leading to alleviation of neutrophilic inflammation in the airway. In humans, the sputum level of G-CSF can be used to stratify patients with asthma with neutrophil-dominated inflammation.

Our results indicated that myelopoiesis-promoting G-CSF and cytokines as the upstream inducing factors are potential diagnostic and therapeutic targets in patients with neutrophilic asthma.
Preservation of renal function in cardiac surgery patients with low cardiac output syndrome: levosimendan vs beta agonists
Authors: Guerrero Orriach Jose Luis , Navarro Arce I. , Hernandez Rodriguez P. , Raigón Ponferrada A. , Malo Manso A. , Ramirez Aliaga M. , Ramirez Fernandez A. , Escalona Belmonte J. J. , Bellido Estevez I. , Gomez Luque A. , Barrera Serrano R. , Toledo Medina C. S. , Rubio Navarro M. , Cruz Mañas J.
Published: November 2019

Background

Some studies have been performed to assess the effects of levosimendan on cardiac function when administered to cardiac surgery patients with low cardiac output syndrome (LCOS) in the immediate postoperative period. Levosimendan is an inotropic agent for the treatment of low cardiac output syndrome that seems to have a protective effect on renal function.

Methods

It is a quasi-experimental study. A total of 100 patients with LCOS received either beta-agonists or levosimendan. We assessed the incidence of postoperative kidney failure in cardiac surgery patients. In patients who had kidney failure at diagnosis of LCOS, we examined whether differences existed in the evolution of kidney failure based on the treatment administered for LCOS. The parameters measured included haemodynamics, oxygen supply, and renal function as assessed by the AKI scale. ANOVA, Student’s t-test and Wilcoxon or Friedman tests were used.

Results

Up to 30% of cardiac surgery patients had kidney failure at diagnosis of LCOS. Kidney failure at discharge from the ICU was more frequent in patients who received beta-agonist drugs as compared to those who received levosimendan (p < 0.05).

Conclusion

The incidence of kidney failure decreased with the postoperative administration of levosimendan to cardiac surgery patients with LCOS, as compared to beta-agonists.

Trial registration

Current Controlled Trials ISRCTN 46058317. Date of registration: 7/10/2019.

Retrospectively registered.
Combined associations of hs-CRP and cognitive function with all-cause mortality among oldest-old adults in Chinese longevity areas: a prospective cohort study
Authors: Chen Chen , Liu Yingchun , Cao Zhaojin , Yin Zhaoxue , Zhao Feng , Lv Yuebin , Liu Zuyun , Mao Chen , Song Shixun , Liu Ling , Qu Yingli , Ji Saisai , Duan Jun , Wang Jiaonan , Kraus Virginia Byers , Zeng Yi , Shi Xiaoming
Published: November 2019

Background

Inflammatory markers, such as high sensitivity C-reactive protein (hs-CRP), and cognitive impairment (CI) are associated with mortality; CRP is related to the deterioration of CI. However, it is still unknown whether these two indices predict mortality independent of each other. Furthermore, their joint effect on all-cause mortality has not been well established, especially in oldest-old adults.

Methods

Based on data from the 2012 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS), we included 1447 oldest-old adults (mean age 84.7 years and 58.7% were female, weighted) with information on hs-CRP (stratified by a cutoff value of 3.0 mg/L) and cognition (quantified by Mini-Mental Status Examination (MMSE) scored according to the personal educational level) at baseline. Mortality was assessed in followed 2014 and 2017 waves. Cox proportional hazards regression models were used, with adjustment for hs-CRP and cognition (mutually controlled) and several traditional mortality risk factors.

Results

During a median follow-up period of 32.8 months (Q1-Q3, 9.7–59.0 months), 826 participants died. Hs-CRP [HR > 3.0 mg/L vs ≤ 3.0 mg/L: 1.64 (95% CI, 1.17, 2.30)] and cognition [HR CI vs normal: 2.30 (95% CI, 1.64, 3.21)] each was independent predictor of all-cause mortality, even after accounting for each other and other covariates. Monotonic and positive associations were observed in combined analyses, in which the highest mortality risk was obtained in elders with both high hs-CRP> 3.0 mg/L and CI [HR: 3.56 (95% CI, 2.35, 5.38)].The combined effects were stronger in male and younger oldest-old (aged 80–89 years).

Conclusion

High hs-CRP and CI, both individually and jointly, were associated with increased all-cause mortality risks in Chinese oldest-old. Intervention strategies for preventing inflammation and maintaining adequate cognitive function may be more important in male and younger oldest-old for reducing mortality risk.
Comparison of radiographic and functional results of die-punch fracture of distal radius between volar locking plating (VLP) and external fixation (EF)
Authors: Zhou Yanqing , Zhu Yanbin , Zhang Xiong , Tian Dehu , Zhang Bing
Published: November 2019

Purpose

The aim of this study is to investigate the radiographic and functional results of die-punch fracture of distal radius treated by volar locking plate (VLP) or external fixation (EF).

Methods

Between January 2015 and June 2018, 87 patients who were treated with EF or VLP were included in this study. At postoperative 6 months and at least 12 months, radiographic and functional outcomes were evaluated, and compared between two groups using SPSS 21.0.

Results

The follow-up period was 15.6 months in average, and at the mean 8.5 weeks bony union was achieved in all patients. At 6-month visit, patients in VLP group had significantly better wrist flexion (79.2° vs. 71.8°) and pronation (79.5° vs. 75.2°) than those in EF group, but the difference was non-significant at the last visit (> 12 months); as for other parameters, no significant differences were observed. No significant difference was found between both groups in term of volar tilt, radial inclination, radial height, ulnar variance, or Gartland–Werley score and DASH. The articular step-off was significantly greater in EF than VLP group (0.6 mm vs. 0.3 mm, p < 0.001). The overall incidence of complications seemed higher in EF group (25% vs. 14%), but not approaching to the statistical significance level.

Conclusions

Patients with VLP fixation of die-punch fractures had better wrist flexion and pronation at 6-month visit and more favorable wrist joint congruence at the last visit, but ultimately their outcome was comparable with those treated by EF.
Comparison of the umbilical cord Blood’s anti-Mullerian hormone level in the newborns of mothers with polycystic ovary syndrome (PCOS) and healthy mothers
Authors: Tadaion Far Faezeh , Jahanian Sadatmahalleh Shahideh , Ziaei Saeideh , Kazemnejad Anoshirvan
Published: November 2019

Background

Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases. At present, the cause of the disease is not fully understood, but many studies have shown that PCOS is associated with genetic and environmental factors. The present study aimed to assess the umbilical cord blood’s Anti-mullerian hormone (AMH) level in the newborns of mothers suffering from PCOS comparing to healthy mothers.

Methods

This prospective cohort study was conducted on 120 pregnant women with PCOS, who were selected through Rotterdam criteria, and 60 healthy pregnant women as the control group. The subjects in each group were divided into obese and non-obese mothers according to their body mass index (BMI) before pregnancy. The cord blood samples were collected from the offsprings on the time of childbirth. Finally, the circulating concentrations of AMH in both sexes of the newborns were determined by specific assays.

Results

The research results showed that the blood level of AMH was higher in the neonates of obese mothers with PCOS comparing to the controls (P < 0.001). Mean AMH level was higher in male neonates born from non-obese PCOS mothers than in the controls (P < 0.001); however, there was not a significant difference in the level of AMH in female neonates between these two groups (P = 0.264). Also the level of the above biomarker was higher in both sexes of the neonates belonging to obese PCOS mothers compared with the neonates born from non-obese PCOS mothers (P < 0.001).

Conclusion(s)

It can be said that the cord blood AMH level of neonates from obese women with PCOS is higher than that in the newborns of non-obese PCOS mothers. Further longitudinal studies are needed to confirm the clinical findings of the present research.
Thy-1 predicts poor prognosis and is associated with self-renewal in ovarian cancer
Authors: Connor Elizabeth V. , Saygin Caner , Braley Chad , Wiechert Andrew C. , Karunanithi Sheelarani , Crean-Tate Katie , Abdul-Karim Fadi W. , Michener Chad M. , Rose Peter G. , Lathia Justin D. , Reizes Ofer
Published: November 2019

Background

Ovarian cancer is the leading cause of gynecologic cancer death in the United States despite effective first-line systemic chemotherapy. Cancer stem cells (CSCs) retain the ability to self-renew and proliferate and may be a means of harboring disease that evades standard treatment strategies. We previously performed a high-throughput screen to assess differential protein expression in ovarian CSCs compared to non-CSCs and observed that Thy-1 was more highly expressed in CSCs. Our primary aim was to validate Thy-1 (CD90) as a cancer stem cell (CSC) marker in epithelial ovarian cancer (EOC), correlate with clinical outcomes, and assess as a potential therapeutic target.

Results

Kaplan Meier (KM) Plotter data were correlated with survival outcomes. Quantitative real-time PCR, flow cytometry, and immunoblots assessed RNA and protein expression. Limiting dilution assays assessed self-renewal capacity and proliferation assays assessed proliferative capacity. RNA in-situ hybridization was performed on patient specimens to assess feasibility. Thy-1 (CD90) is more highly expressed in ovarian CSCs than non-CSCs, in EOC compared to benign ovarian epithelium (P < 0.001), and is highest in serous EOC (P < 0.05). Serous ovarian cancers with high Thy-1 expression have poorer outcomes (median PFS 15.8 vs. 18.3 months, P = 0 < 0.001; median OS 40.1 v. 45.8 months, P = 0.036). Endometrioid ovarian cancers with high Thy-1 have poorer PFS, but no difference in OS (upper quartile PFS 34 v. 11 months, P = 0.013; quartile OS not reached, P = 0.69). In vitro, Thy-1 expression is higher in CSCs versus non-CSCs. EOC cells with high Thy-1 expression demonstrate increased proliferation and self-renewal. Thy-1 knockdown in EOC cells decreases proliferative capacity and self-renewal capacity, and knockdown is associated with decreased expression of stem cell transcription factors NANOG and SOX2. RNA in situ hybridization is feasible in ovarian cancer tissue specimens.

Conclusions

Thy-1 is a marker of ovarian CSCs. Increased expression of Thy-1 in EOC predicts poor prognosis and is associated with increased proliferative and self-renewal capacity. Thy-1 knockdown decreases proliferative and self-renewal capacity, and represents a potential therapeutic target.
Highlights and recent developments in skin allergy and related diseases in EAACI journals (2018)
Authors: Akdis C. A. , Bousquet J. , Grattan C. E. , Eigenmann P. A. , Hoffmann-Sommergruber K. , Agache I. , Jutel M.
Published: November 2019

The European Academy of Allergy and Clinical Immunology (EAACI) supports three journals: Allergy, Paediatric Allergy and Immunology as well as Clinical and Translational Allergy. The major goals of EAACI include (i) supporting health promotion in which the prevention of allergy and asthma plays a critical role and (ii) disseminating the knowledge of allergy to all stakeholders including the EAACI junior members. Substantial progress was made in 2018 in the identification of basic mechanisms of atopic dermatitis and urticaria and the translation of these mechanisms into clinics. Many large epidemiologic studies and meta-analyses have been the highlights of the last year.
Acceptability, feasibility, and efficacy of Internet cognitive behavioral therapy (iCBT) for pediatric obsessive-compulsive disorder: a systematic review
Authors: Babiano-Espinosa Lucía , Wolters Lidewij H. , Weidle Bernhard , op de Beek Vivian , Pedersen Sindre A. , Compton Scott , Skokauskas Norbert
Published: November 2019

Background

Obsessive-compulsive disorder (OCD) is a chronic mental health disorder characterized by recurring obsessions and compulsions affecting 1–3% of children and adolescents. Current treatment options are limited by accessibility, availability, and quality of care. New technologies provide opportunities to address at least some of these challenges. This paper aims to investigate the acceptability, feasibility, and efficacy of traditional cognitive behavioral therapy with Internet cognitive behavioral therapy (iCBT) for pediatric OCD according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Method

We searched EMBASE, Medline, PsycINFO, CENTRAL, LILACS, CINAHL, and Scopus. Results include articles from 1987 to March 2018. Main inclusion criteria were patients aged 4–18, primary diagnosis of OCD, and iCBT.

Results

Of the 2323 unique articles identified during the initial search, six studies with a total of 96 participants met our inclusion criteria: three randomized controlled trials, one single-case multiple-baseline design, one open-label trial, and one case series. Four studies reported a significant decrease in OCD severity on the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) following iCBT, one study reported significant decrease in CY-BOCS scores for iCBT relative to waitlist, and the case series reported (some) symptom reduction in all participants. Six studies reported high rates of feasibility, and five studies reported good acceptability of iCBT.

Conclusion

At present, evidence regarding acceptability, feasibility, and efficacy of iCBT for pediatric OCD is limited. Results are promising but need to be confirmed and refined in further research.

Systematic review registration

PROSPERO CRD4201808587
On an initial inverse problem for a diffusion equation with a conformable derivative
Authors: Binh Tran Thanh , Luc Nguyen Hoang , O’Regan Donal , Can Nguyen H.
Published: November 2019

In this paper, we consider the initial inverse problem for a diffusion equation with a conformable derivative in a general bounded domain. We show that the backward problem is ill-posed, and we propose a regularizing scheme using a fractional Landweber regularization method. We also present error estimates between the regularized solution and the exact solution using two parameter choice rules.
An experimental investigation on the effect of adhesive distribution on strength of bonded joints
Authors: Pisharody A. P. , Blandford B. , Smith D. E. , Jack D. A.
Published: November 2019

Adhesive joints are widely used due to their higher strengths, lower weights, lesser expenses and ease of fabrication than other methods of joining. Hence, they are used extensively in aerospace and automobile industries. High quality bonds require the use of fixtures which are essential to ensure proper curing and to attain uniform thickness. Improper adhesive application and method of fixturing can cause irregularities in the distribution of the adhesive along the overlap which could affect the joint strength. This is especially critical for aerospace components as the replacement of parts can be costly and time consuming. This paper presents a nondestructive test (NDT) methodology to quantify the bonded joints where the adhesive does not completely cover the overlap area. Single lap adhesive joints with carbon fiber adherents were fabricated using a two-part epoxy based adhesive. The adhesive region was fabricated to have various shapes including elliptical and circular of different sizes and a joint with full coverage for comparison. Polytetrafluoroethylene (PTFE) cutouts were used to mask regions of adhesive to achieve the desired coverage pattern. After fabrication all samples were ultrasonically scanned with a 10 MHz spherically focused immersion transducer using pulse-echo ultrasonics to determine the actual as tested adhesive distribution shape. The scans were able to resolve the shape of adhesive distribution across the overlap region of 25.4 × 25.4 mm and were correlated with the actual adhesive distribution at the interface after lap shear tests. Lap shear tests were then performed on the samples fabricated and the samples were loaded to failure. It was found that the shape and the orientation of the adhesive shape relative to the loading direction had an effect on failure strength.
Success factors for high-quality oak forest (Quercus robur, Q. petraea) regeneration
Authors: Mölder Andreas , Sennhenn-Reulen Holger , Fischer Christoph , Rumpf Hendrik , Schönfelder Egbert , Stockmann Johannes , Nagel Ralf-Volker
Published: November 2019

Background

Within the framework of close-to-nature forestry, oak forest (Quercus robur,Q. petraea) regeneration techniques that consider both silvicultural and nature conservation demands have become a very important issue. While there are many experimental and local studies that aim at disentangling the relationships between different environmental and silvicultural factors and the success of oak regeneration, systematic supra-regional studies at the greater landscape level are missing so far.

Against this background, the first objective (a) of this study was to present an efficient and sufficiently accurate sampling scheme for supra-regional forest regrowth inventories, which we applied to young oaks stands. The second, and major, objective (b) was to identify the crucial success factors for high-quality oak forest regeneration in northwest Germany.

Results

Objective (a): Factors that have been identified as potentially crucial for the success or failure of oak regeneration were either included in a field inventory procedure or extracted from forest inventory databases. We found that the collected data were suitable to be analyzed in a three-step success model, which was aimed at identifying the crucial success factors for high-quality oak forest regeneration.

Objective (b): Our modeling procedure, which included a Bayesian estimation approach with spike-and-slab priors, revealed that competitive pressure from the secondary tree species was the most decisive success factor; no competition, or low competition by secondary tree species appeared to be particularly beneficial for the success of high-quality oak regeneration. Also fencing and the absence of competitive vegetation (weeds, grass, bracken) seemed to be beneficial factors for the success of oak regeneration.

Conclusions

Trusting in biological automation was found to be mostly useless regarding economically viable oak forest regeneration. To efficiently organize oak regeneration planning and silvicultural decision-making within a forest enterprise, it is strongly recommended to initially evaluate the annual financial and personnel capacities for carrying out young growth tending or pre-commercial thinning and only then to decide on the extent of regenerated oak stands. Careful and adaptive regeneration planning is also indispensable to secure the long-term ecological continuity in oak forests. Oak regeneration should therefore preferably take place within the close vicinity of old oak stands or directly in them. The retention of habitat trees is urgently advised.
Standardization of the size and shape of virtual human body for apparel products
Authors: Kim Hye Suk , Choi Hee Eun , Park Chang Kyu , Nam Yun Ja
Published: November 2019

International virtual human body (VHB) standards from the International Organization for Standardization (ISO) specifically used in virtual garment systems in the apparel field, as suggested in ISO/TC 133/WG 2 (Working group 2), contain fundamental content regarding definitions of terms, attributes of composition, and the expression and alteration of VHBs. As the first attempt in the series of international standards dealing with VHBs, this study has dealt with fundamental content related to VHB size. Additional standardization is required to allow the size and shape of VHB to be reproducible. Therefore, this study suggests academic and industrial requirements from the perspective of standardization to identify and solve issues regarding the reproduction of human bodies in terms of VHB size and shape. This study is meaningful in that it provides an overview of current VHB standardization efforts, related proceedings, and additionally required assignments. The suggested industrial and academic requirements are anticipated to be helpful in the systematic development and utilization of VHB and general standardization work.
A feasibility randomised controlled trial of short-term fasting prior to CAPOX chemotherapy for stage 2/3 colorectal cancer: SWiFT protocol
Authors: Shingler Ellie , Perks Claire , Herbert Georgia , Ness Andy , Atkinson Charlotte
Published: November 2019

Background

Capecitabine and oxaliplatin (CAPOX) chemotherapy is a standard treatment for stage 2/3 colorectal cancer. Treatment is associated with dose-limiting toxicities such as neutropenia, vomiting, diarrhoea, and stomatitis. Short-term fasting prior to chemotherapy may help protect normal cells from the toxic effects of chemotherapy by allowing them to conserve energy for maintenance and repair. However, there is a lack of evidence to support the efficacy of short-term fasting in protecting against chemotherapy-related toxicities in humans, and it is not known whether people due to undergo chemotherapy will be willing and able to follow a short-term fast. Preliminary data confirming this is feasible are required before adequately powered trials can be designed and conducted.

Methods

The short-term, water only, fasting trial (SWiFT) is a two-armed feasibility randomised controlled trial, aiming to recruit 30 people scheduled to begin routine treatment with CAPOX chemotherapy for stage 2/3 colorectal cancer. Participants will be randomly allocated, in a 1:1 ratio, to either a 36-h fast or standard dietary advice prior to chemotherapy administration for the first 3 cycles of chemotherapy. The primary outcome measures will assess the feasibility of the trial and include: adherence to intervention, recruitment, retention, and data completion rates as well as the acceptability of the intervention which will be qualitatively assessed. The secondary outcome measures aim to provide further information on possible outcomes of interest for a definitive trial and include side effects of chemotherapy, quality of life, markers of cellular metabolism and inflammation, appetite, and sarcopenia.

Discussion

It is not known whether it is possible to recruit to a trial of short-term fasting in this population, or whether participants would be able to adhere to the intervention. Therefore, we aim to test the feasibility of a pre-chemotherapy, 36-h, water-only fast in people receiving CAPOX chemotherapy for stage 2/3 colorectal cancer.

Trial registration

This trial has been registered with the ISRCTN Registry. Trial registration no: ISRCTN17994717. Date of registration: 23 October 2018. URL: http://www.isrctn.com/ISRCTN17994717