bluuebunny/crossref_metadata_2025 huggingface dataset:
10-Year Outcomes after Allogeneic Hematopoietic Cell Transplantation (HCT) in Adolescent and Young Adults (AYA)
Authors: Hanna Rabi , Rybicki Lisa , Abounader Donna , Bolwell Brian J. , Dean Robert M , Duong Hien K. , Flagg Aron , Gerds Aaron T. , Hamilton Betty K. , Hill Brian T. , Kalaycio Matt E. , Sobecks Ron , Majhail Navneet S.
Published: October 2019

AYAs with cancer have been designated as a vulnerable population by the National Cancer Institute. This group, defined by the ages of 16-39 years, has not enjoyed the same survival improvements over the past several decades as older and younger cohorts. The reasons for outcome disparities among AYA leukemia patients are not well understood. Recent studies have compared outcomes of AYA HCT recipients with younger and older cohorts and reported no lag in survival improvements over time. However, long-term survival after allogeneic HCT in this age group has not been well described. We analyzed outcomes for 226 AYA patients with acute and chronic leukemia, myelodysplastic syndromes, aplastic anemia and lymphoma who were transplanted at our institution from 1/2000-3/2013. The median age at HCT was 29 years (range 15-39) and their median follow up was 5 years (range, <1– 14). Most patients had acute leukemia (65%) and received HCT using related donors (40%) or unrelated donors (60%, including 20 UCB). 92% patients received myeloablative conditioning, most commonly using Bu+Cy±VP16 (50%), TBI+VP16 (17%) or Cy+TBI (13%). Table shows 10 year outcomes in our cohort. The 100 day cumulative incidence of grade 2-4 acute GVHD was 42% (95% CI, 36-49) and 2 year incidence of chronic GVHD was 41% (95% CI, 34-47%). The most common causes of death were relapse (36%), infection (18%) and acute GVHD (14%). In multivariate analyses, risk factors associated with inferior overall survival included greater number of prior chemotherapy regimens, high HCT-CI risk score, presence of active disease at HCT, diagnosis of ALL, MDS or Hodgkin lymphoma, CMV positive serostatus and use of myeloablative conditioning. Since survival started to plateau at 2 years post-transplant, we compared the overall survival of 2 year survivors with that of the general age-, sex- and race-matched general population. Survival continued to remain significantly lower than the general population till 10 years post-HCT (Figure). In conclusion, AYAs who receive allogeneic HCT have favorable long-term survival. However, non-relapse mortality continues to be a significant issue in this population and providers should pay attention to screening and prevention of late complications.

Table: 10 year outcomes after allogeneic HCT in AYAs Probability (95% CI) Overall survival 43% (35-50) Relapse free survival 36% (29-43) Relapse* 29% (22-35) Non-relapse mortality* 37% (30-44) Second cancers* 7% (2-12) * Cumulative incidence estimates

Figure: Survival of AYA HCT recipients who were alive at 2 years vs. survival of age-, sex-, and race-matched general population Figure:. Survival of AYA HCT recipients who were alive at 2 years vs. survival of age-, sex-, and race-matched general population

Disclosures

No relevant conflicts of interest to declare.
Ineffective Erythropoiesis Is the Major Cause of Microcytic Anemia in the TSAP6/Steap3 Null Mouse Model
Authors: Blanc Lionel , Papoin Julien , Vidal Michel , Amson Robert , Telerman Adam , An Xiuli , Mohandas Narla
Published: October 2019

STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) is the major ferrireductase in the erythroblast. Also named TSAP6 (Tumor Supressor Activated Pathway 6) after it had been found to play a role in cancer, its total ablation in the mouse leads to severe microcytic and hypochromic red cells with moderate anemia. The protein function appears conserved among mammals, as patients carrying a nonsense mutation in the TSAP6/STEAP3 gene have been reported with hypochromic anemia. Here, we investigated the mechanism leading to the anemia. In the present study, using the TSAP6/Steap3 knockout mice, we undertook a comprehensive hematologic characterization of the red cell compartment. Red cell indices derived using ADVIA 120 blood counter confirmed the hypochromic microcytic anemia phenotype with a marked reduction in the mean corpuscular volume (MCV; 21.5fL ± 1.3fL in knockout vs 45.2fL ± 1.5fL in wild-type X ± SD, p<0.001) and mean cell hemoglobin content (MCH; 5.8pg ± 0.1pg vs 14.5pg ± 0.1pg, p<0.001). The reticulocyte count was marginally elevated (5.7% ± 1.2% vs 2.6% ± 0.4%, p<0.05) indicating that the anemia is proliferative. By phase contrast microscopy and transmission electron microscopy, we observed marked anisocytosis as well as the presence of fragmenting erythrocytes. Consistent with this observation, we found by ektacytometry decreased membrane mechanical stability of knockout red cells. Interestingly, we were unable to document significant changes in the expression levels of the major skeletal and transmembrane proteins to account for this decrease in the membrane stability.

As defects in either the production or destruction of red cells can lead to anemia, we measured red cell survival and erythropoiesis in these mice. No differences in red cell survival could be documented using biotin labeled red cells implying that decreased survival cannot account for the anemia. However, when we monitored erythropoiesis using Ter119, CD44 and Forward Scatter (FSC) as markers of terminal differentiation, we found a decreased number of proerythroblasts in the bone marrow of TSAP6/Steap3-/- animals (2.20% ± 0.49% vs 4.07% ± 0.77%, p<0.01). In addition, progression from the proerythroblastic to the orthochromatic stage was also affected, with accumulation of cells at the polychromatic stage. These findings imply that ineffective erythropoiesis is the dominant cause of anemia in these mice and that TSAP6/Steap3 may play a role during erythropoiesis beyond its role as ferrireductase. It is interesting to note that while the phenotype of microcytic red cells with decreased hemoglobin content in the TSAP6/Steap3 null mouse is similar to red cells in thalassemic and porphyria mice, there are distinct differences in the etiology of the hematologic phenotype.

Disclosures

No relevant conflicts of interest to declare.
Age As an Independent Clinical Predictor for Vitamin D Deficiency in Sickle Cell Disease
Authors: Han Jin , Saraf Santosh L. , Abbasi Taimur , Zhang Xu , Molokie Robert E. , Hassan Johara , Gowhari Michel , Alhandalous Chaher , Machado Roberto F. , Gordeuk Victor R.
Published: October 2019

Background: Vitamin D deficiency (VDD) is highly prevalent among patients with sickle cell disease (SCD). Although little is known about the risk factors for VDD in SCD, it has been shown that VDD is associated with chronic pain, bone fragility, and pulmonary function in SCD. In this study we investigated the potential clinical predictors for VDD in patients with SCD.

Method: In a retrospective, cross-sectional analysis, a total of 167 adults with SCD treated at the University of Illinois Medical Center with a baseline 25-hydroxy vitamin D (25-OHD) measurement were screened. Clinical variables were recorded from a clinic visit at least four weeks from a vaso-occlusive pain episode or red blood cell transfusion. Statistical association between 25-OHD and other clinical parameters were investigated.

Results: After stratifying the patients based on 25-OHD levels, we observed the median age was significantly younger in patients with lower 25-OHD levels (Table 1). When analyzing different age groups by Kruskal Wallis analysis, 25-OHD levels were significantly elevated in patients ≥ 40 years old (Figure 1). When using Spearman correlation analysis, the 25-OHD levels as a continuous variable positively correlated with increasing age (p<0.001); they also showed a significant negative relationships with creatinine clearance, total bilirubin, platelet count, and white blood cell count (Table 2). Using ordinal logistic regression, age was an independent predictor of 25-OHD levels, as a three-categorical variable, in SCD (OR 0.55, 95% CI: 0.38 – 0.81; p =0.002) after adjusting for gender, creatinine clearance, and vitamin D supplementation (Table 3), which means that younger patients has higher chance of VDD. In the patients with VDD (25-OHD <20 ng/mL), weekly supplementation with oral ergocalciferol (50,000 units for twelve weeks) substantially improved 25-OHD levels (9.9 vs 23.7 ng/mL, p<0.0001, N=24). During a median of 40-month follow-up (range 0 to 96 months), thirteen patients died, but the log rank test or multivariate Cox regression analysis failed to show statistical significance between 25-OHD levels and mortality after adjusting ESRD and baseline vitamin D supplementation, likely due to a short follow-up period and a small sample size.

Summary: Lower 25-OHD levels were associated with younger age in patients with SCD, especially patients younger than 40 years old. One possible explanation is that lower 25-OHD levels may be linked to higher mortality in SCD, but future research is needed to clarify the association between VDD and mortality in SCD.

Disclosures

No relevant conflicts of interest to declare.
Posttranslational Modification in Megakaryocytes Regulates β1 Integrin Expression, Migration and Platelet Production in Vivo
Authors: Giannini Silvia , Adelman Max , Begonja Antonija Jurak , Hoffmeister Karin M
Published: October 2019

Platelet recovery following bone marrow transplant and radiochemotherapy is crucial to prevent bleeding complications. Defects in glycosylation have been associated with decrease in blood platelet counts. However, the role of posttranslational modification in platelet production remains elusive. We here investigated the role of β1,4 galactosyltransferase 1 (β4GalT1), the key glycosyltransferase regulating lactosaminoglycan (LacNAc or βGal1,4 GlcNAc) expression by adding galactose (Gal) to terminal N-acetylglucosamine (GlcNAc), in platelet production. Stromal cell-derived factor 1 (SDF-1), but not thrombopoietin promotes megakaryocyte (MK) migration towards the bone marrow sinusoids, thereby increasing platelet production. SDF-1 (CXCL12) upregulated LacNAc expression in fetal liver wild type (WT), but not β4galt1-null megakaryocytes (MKs) lacking β4GalT1, suggesting that SDF-1 promotes LacNAc expression in vivo to regulate MK migration and platelet production. In support of this hypothesis, β4galt1-null mice had severe macrothrombocytopenia with increased bone marrow MK numbers, but normal platelet clearance. Ploidy, expression of the major glycoproteins (GPIbα/V/IX and αIIbβ3) and the surface expression of the SDF-1 receptor CXCR4 were normal in β4galt1-null bone marrow MKs. However, β4galt1-null bone marrow MKs had increased surface and total β1 integrin expression, as determined by flow cytometry, immunoblot and immunofluorescence. Mature CD42b/CD41 positive β4galt1-null MKs co-localized poorly with endoglin positive bone marrow sinusoids (49.9 ± 2.1 %), compared to WT MKs (72.4 ± 0.6 %). Expression of laminin, the major β1 integrin ligand, was upregulated in β4galt1-null MKs, suggesting that loss of LacNAc expression on β1 integrin increased its function. To exclude an extrinsic contribution to the failure of β4galt1-null MKs to migrate, β4galt1-null fetal liver (E14.5) hematopoietic cells (FLHCs) were transplanted in lethally irradiated WT mice. Transplanted β4galt1-null FLHCs restored bone marrow MKs, but failed to migrate to sinusoids and produce circulating platelets. In marked contrast, production of β4galt1-null white blood cells was normal. Together, our results suggest that SDF-1 upregulates β4GalT1-dependent LacNAc expression to promote MK migration and interaction with BM sinusoids, likely regulating MK β1 integrin expression and interaction with components of the extracellular matrix, specifically laminin. Understanding of the mechanisms regulating posttranslational modifications induced by various hematopoietic stimulating chemokines and cytokines will contribute to better platelet recovery following bone marrow transplant and radiochemotherapy.

Disclosures

No relevant conflicts of interest to declare.
Neutrophil Mobilization into Peritoneal Fluid
Authors: FRUHMAN GEORGE J.
Published: October 2019

Rats were injected intraperitoneally with various solutions, and the local cellular responses were studied using quantitative methods. Contrary to reports in the literature, pure saline did not evoke a local neutrophilia after it was injected intraperitoneally. Under similar conditions, bacterial lipopolysaccharides proved to be highly effective. Trace doses were most effective; larger doses caused a marked diminution of the response. Furthermore, a variety of nonbacterial substances were impotent when tested under comparable conditions.
THE TREATMENT OF LYMPHOBLASTIC LEUKEMIA WITH CRUDE MYELOKENTRIC ACID
Authors: MILLER F. R. , HERBUT P. A. , JONES H. W.
Published: October 2019

Eight cases of blastic lymphoid leukemia have been treated with myelokentric acid in crude form, because hypothetically in blastic lymphoid leukemia there is a deficiency of this material. The crude myelokentric acid was used because it was more easily obtained than partially purified material. Purification of biologically active materials by methods of extraction and precipitation necessarily results in a considerable loss of material. Thirteen partial remissions occurred following the administration of crude myelokentric acid. Seven of the 8 patients have died, and 5 necropsies were performed.

The necropsy material adds further weight to the belief that the remissions were induced by the myelokentric acid in that in all 5 necropsies there was a definite alteration in the histologic morphology as contrasted with the findings in the necropsies of the controls.

It seems inadvisable, however, to treat a large number of patients with this material because it is crude, it is relatively unavailable, and no standard dose has yet been devised.
CONTRIBUTION TO THE PATHOGENESIS OF HEMOPHILIA
Authors: PAVLOVSKY ALFREDO
Published: October 2019

The causes of the delayed coagulation of hemophilic blood seem to become clearer as time advances. On one side we have the investigations of the school of Minot, indicating a deficit in the globulin fraction; and on the other side are the works of those who maintain that there exists an excess of anticoagulant substances. We support the latter theory, although in our opinion the two theories do not contradict each other, since it might be possible that this anticoagulant substance would act on the globulin fraction diminishing its coagulant power. This substance could be identified with the anticephalin fraction of Tocantins.

With the idea that this substance might be less stable than the coagulant fractions (fibrinogen, prothrombin, and thromboplastin) we have tried to render it inactive by keeping the blood in a refrigerator for a certain length of time. Inactivity was obtained in some of our experiments. We know that the stability of this substance varies from one patient to the other, but we have not been able to fix the cause of these variations.

In conclusion, we consider that other means of neutralizing the action of this anticoagulant substance should be investigated. This inactivity once obtained, we should have advanced far in solving the intricate problem of hemophilia.
THE PATHOLOGY OF INFECTIOUS MONONUCLEOSIS
Authors: CUSTER R. PHILIP , SMITH EDWARD B.
Published: October 2019

This pathologic study is based on 9 autopsies and many biopsies in cases of infectious mononucleosis.

The gross changes were almost exclusively confined to enlargement of lymphoid tissues, especially the spleen. Nasopharyngeal lymphoid hyperplasia was constant, in one instance suggesting tumor. Other tissues presented no significant gross features related to the primary disease except for (1) rather consistent enlargement of the liver, (2) infrequent icterus, and (3) occasional cutaneous rash. Histologic observations revealed more or less generalized lesions resembling those of certain known virus diseases, notably perivascular aggregates of normal and abnormal lymphocytes. Reaction of this type inconstantly involved all tissues studied except the bone marrow; here lymphocytes were virtually absent in sections, but were present in aspirated marrow because of dilution with peripheral blood.

More specific changes were invariably noted in lymphoid tissues. The abnormal lymphocyte characteristic of the disease could be identified in thin, lightly stained sections. Lymph node reactions varied from a predominantly follicular hyperplasia to a blurred pattern simulating a malignant lymphoma; the latter was due to a lymphocytic and reticulo-endothelial proliferation in the medullary cords. The spleen displayed a lymphocytic infiltration in the thinned capsule and trabeculae, frequently dissolving the latter and rendering the organ liable to rupture. The pattern was partially effaced in most instances and the follicles widely spaced. Blood sinuses contained considerable numbers of normal and abnormal lymphocytes, and accumulations of these cells constantly cuffed intratrabecular arteries and lay beneath the intima of veins. Tonsils displayed ulceration and necrosis in several cases, and the lymphocytic proliferation closely resembled malignant tumor in a tonsil that enlarged rapidly.

A pneumonic exudate in 1 case was almost exclusively of round cell type, while in another the pneumonia was of the usual lobular type with a neutrophilic exudate. Small myocardial infiltrates which we noted probably explain the electrocardiographic changes described in infectious mononucleosis. Other findings of particular interest were the periportal lymphoid collars in the liver which sometimes attained the proportions seen in leukemia, and the presence of meningo-encephalitis in 4 of the 6 brains examined.

We believe that the majority of cells in the lymphocytic "infiltrates" of connective tissues and the perivascular collars are metaplastic rather than inwandering, i.e., that they are formed in situ and stem from cells of the reticulo-endothelial system.
THE EFFECT OF FOLIC ACID ON THE TOXICITY OF ITS ANALOGUE 4-AMINOPTEROYLGLUTAMIC ACID (AMINOPTERIN)
Authors: HIGGINS GEORGE M. , STEMBER MURIEL , MONSEN HARRY
Published: October 2019

A study of some of the toxic reactions of 4-aminofolic acid together with the modifications of these reactions induced by giving varying amounts of folic acid daily to white rats is reported.

Seven groups of young male rats ranging in weight from 110 to 130 Gm. were arranged. Aminopterin (4-aminofolic acid) was given intraperitoneally, in amounts equivalent to 50 micrograms daily, to all rats of six of these seven groups. Folic acid was given by mouth to these animals in such amounts as to provide 5, 10, 20, 30 or 50 mg. daily to each animal respectively of five of the six groups receiving aminopterin. One group received the analogue without the vitamin. One group of 8 animals received neither the vitamin nor its analogue.

Observations continued for six days, when all surviving animals were killed and necropsy was performed. Data were assembled on the appetite, body weights, the weights of adrenals, thymus and spleen, the distribution of leukocytes in the peripheral blood and the changes in the bone marrow. The following conclusions seem warranted:

1. Aminopterin is extremely toxic and incites within six days anorexia, extreme diarrhea with atony of the entire gastro-intestinal tract, adrenal hyperplasia, atrophy of the thymus and spleen, and an inhibition to development of myeloid cells in the bone marrow.

2. Small amounts of folic acid are essentially without effect on the toxicity of that amount of the analogue we chose to administer.

3. Larger amounts of folic acid daily (30 mg.) proved effective in essentially inhibiting the development of the severe toxic reactions for the six-day period.

4. The severe toxicity of aminopterin does not manifest itself until the third or or fourth day of its daily administration. The onset of these symptoms is thereafter extremely rapid.

5. Thirty milligrams of folic acid daily will not indefinitely counteract the toxic symptoms induced by 50 micrograms of aminopterin. In our experience, within twelve to fourteen days, the characteristic syndrome will appear in spite of the continuous administration of the vitamin.
FETAL AND ADULT HEMOGLOBINS IN THE BLOOD OF INFANTS AFFECTED WITH HEMOLYTIC DISEASE OF THE NEWBORN
Authors: PONDER ERIC , LEVINE PHILIP
Published: October 2019

A method is described by means of which the rapidly denatured adult Hb can be separated from the slowly denatured fetal Hb by denaturing with alkali and precipitating the denatured material at its isoelectric point. When applied to 15 normal cord bloods and to the cord bloods of 15 infants affected with hemolytic disease of the newborn, the method showed no significant difference in the percentage of fetal Hb present.
Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer
Authors: Cadranel Jacques , Canellas Anthony , Matton Lise , Darrason Marie , Parrot Antoine , Naccache Jean-Marc , Lavolé Armelle , Ruppert Anne-Marie , Fallet Vincent
Published: October 2019

Immune checkpoint inhibitor-related pneumonitis (ICI-P) during cancer treatment is rarely observed (<5%). ICI-P is more often observed in patients with nonsmall cell lung cancer (NSCLC) than in those with other cancers. Likewise, it is more common in those receiving programmed cell death (PD)-1/PD-1 ligand inhibitors rather than cytotoxic T-lymphocyte antigen (CTLA)-4 inhibitors alone. The frequency of ICI-P is higher when anti-PD-1 and anti-CTLA-4 are administered concomitantly. Despite the low fatality rate (≈13%), ICI-P is the leading cause of ICI-related deaths. This narrative review focuses on the epidemiology, clinical and radiological presentation and prognosis of ICI-P occurring in patients, especially those with advanced NSCLC. Emphasis is placed on the differences in terms of frequency or clinical picture observed depending on whether the ICI is used as monotherapy or in combination with another ICI or chemotherapy. Other pulmonary complications observed in cancer patients, yet not necessarily immune-related, are reviewed, such as sarcoid-like granulomatosis, tuberculosis or other infections. A proposal for pragmatic management, including differential diagnosis and therapeutic strategies, is presented, based on the ICI-P series reported in the literature and published guidelines.
Correction to: Assessing the leaching behavior of different gunshot materials in natural spring waters
Authors: Fäth Julian , Göttlein Axel
Published: October 2019

The authors note a correction to the original article [1]. Table 3 legend is incorrectly processed. This article presents the corrected version of Table 3.
Correction to: African evolutionary history inferred from whole genome sequence data of 44 indigenous African populations
Authors: Fan Shaohua , Kelly Derek E. , Beltrame Marcia H. , Hansen Matthew E. B. , Mallick Swapan , Ranciaro Alessia , Hirbo Jibril , Thompson Simon , Beggs William , Nyambo Thomas , Omar Sabah A. , Meskel Dawit Wolde , Belay Gurja , Froment Alain , Patterson Nick , Reich David , Tishkoff Sarah A.
Published: October 2019

Following publication of the original article [1], a typographical error in the formula for calculating di in the “Scans for local adaptation” subsection in the Method section, was identified. The correct formula should be
A national atlas of tsetse and African animal trypanosomosis in Mali
Authors: Diarra Boucader , Diarra Modibo , Diall Oumar , Bass Boubacar , Sanogo Youssouf , Coulibaly Etienne , Sylla Mahamadou , Zhao Weining , Paone Massimo , Cecchi Giuliano
Published: October 2019

Background

Tsetse-transmitted trypanosomosis is a deadly, neglected tropical disease and a major challenge for mixed crop-livestock agriculture in sub-Saharan Africa. It is caused by several species of the genusTrypanosoma. Information on the occurrence of tsetse flies and African animal trypanosomosis (AAT) is available for different areas of Mali. However, these data have never been harmonized and centralized, which prevents the development of comprehensive epidemiological maps and constrains an evidence-based planning of control actions. To address this challenge, we created a dynamic geo-spatial database of tsetse and AAT distribution in Mali.

Methods

A digital repository containing epidemiological data collected between 2000 and 2018 was assembled. In addition to scientific publications, the repository includes field datasheets, technical reports and other grey literature. The data were verified, harmonized, georeferenced and integrated into a single spatially-explicit database.

Results

For the tsetse component, approximately 19,000 trapping records, corresponding to 6000 distinct trapping locations and 38,000 flies were included in the database.Glossina palpalis gambiensiswas the most widespread and abundant species, and it was found in the southern, southern-central and western parts of the country.Glossina tachinoideswas only found in the South. Only a few specimens ofGlossina morsitans submorsitanswere detected. For the AAT component, approximately 1000 survey records were included, corresponding to 450 distinct survey sites and 37,000 tested bovines. AAT was found in all surveyed regions, although data for the tsetse-free North and North-East are lacking.Trypanosoma vivaxandTrypanosoma congolensewere the dominant species, whileTrypanosoma bruceiinfections were much less numerous.

Conclusions

The atlas of tsetse and AAT in Mali provides a synoptic view of the vector and disease situation at the national level. Still, major geographical gaps affect the North, the North-East and the West, and there is also a severe lack of data over the past five years. Trypanosomosis remains a major animal health problem in Mali. However, despite its prevalence and distribution, monitoring and control activities are presently very limited. Efforts should be made to strengthen the progressive control of AAT in Mali, and the atlas provides a new tool to identify priority areas for intervention.
Quantitative proteomic analysis and functional characterization of Acanthamoeba castellanii exosome-like vesicles
Authors: Lin Wei-Chen , Tsai Chia-Yun , Huang Jian-Ming , Wu Shang-Rung , Chu Lichieh Julie , Huang Kuo-Yang
Published: October 2019

Background

Pathogenic protozoans use extracellular vesicles (EVs) for intercellular communication and host manipulation.Acanthamoeba castellaniiis a free-living protozoan that may cause severe keratitis and fatal granulomatous encephalitis. Although several secreted molecules have been shown to play crucial roles in the pathogenesis ofAcanthamoeba, the functions and components of parasite-derived EVs are far from understood.

Methods

Purified EVs fromA. castellaniiwere confirmed by electron microscopy and nanoparticle tracking analysis. The functional roles of parasite-derived EVs in the cytotoxicity to and immune response of host cells were examined. The protein composition in EVs fromA. castellaniiwas identified and quantified by LC-MS/MS analysis.

Results

EVs fromA. castellaniifused with rat glioma C6 cells. The parasite-derived EVs induced an immune response from human THP-1 cells and a cytotoxic effect in C6 cells. Quantitative proteomic analysis identified a total of 130 proteins in EVs. Among the identified proteins, hydrolases (50.2%) and oxidoreductases (31.7%) were the largest protein families in EVs. Furthermore, aminopeptidase activities were confirmed in EVs fromA. castellanii.

Conclusions

The proteomic profiling and functional characterization of EVs fromA. castellaniiprovide an in-depth understanding of the molecules packaged into EVs and their potential mechanisms mediating the pathogenesis of this parasite.
Correction to: MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence
Authors:   MASK study group, Bousquet J.
Published: October 2019

Following publication of the original article [1], the authors reported that one of the collaborators’ names was spelled incorrectly. In this Correction the incorrect and correct author name are shown. In the author list of this Correction article, only the corresponding author and institutional author are presented.
Early outcomes of tapering jejunoplasty by antimesenteric seromuscular stripping and mucosal inversion for proximal jejunal atresia
Authors: Marei Mahmoud Marei , Abouelfadl Mohamed Hamed , Rawwash Ahmed Arafa Elsayed , Seleim Hamed Mahmoud , Mahmoud Wesam Mohamed , Yassin Tamer Yassin Mohamed , El-Tagy Gamal Hassan
Published: October 2019

Background

High jejunal atresia is associated with significant dilatation of the proximal segment. This poses two problems: (a) calibre discrepancy with the distal unused segment and (b) hypomotility causing stasis. Tapering jejunoplasty/enteroplasty could offer a practical solution in selected cases, leading to early establishment of feeds. This work aims to evaluate the outcome of tapering jejunoplasty including its effect on establishing enteral feeding in neonates with proximal jejunal atresia.

Results

Twenty-two neonates with jejunal atresia (types I, II and IIIa) were reviewed. Cases with multiple atresia, apple-peel variant and meconium ileus were excluded. The included cases fell retrospectively into two groups: group A (13 cases)—very proximal atresia and significant dilatation and group B (9 cases)—mid/distal jejunal atresia. For group A, we excised only the distal tip of the dilated bowel and stripped a seromuscular triangle up to the duodenojejunal flexure and inverted the mucosa along the antimesenteric border, followed by an end-to-oblique anastomosis. For group B, we performed a standard excision of a short proximal segment and an end-to-oblique anastomosis. There was no significant difference in the gestation age or birth weight between both groups. The mean operative time was 90 min for group A and 60 min for group B. The duration until full enteral feeds became tolerated, and parenteral nutrition was weaned accordingly was shorter in group A (mean 10.8 days) as compared to group B (mean 14.5 days), p = 0.045.

Conclusion

Tapering jejunoplasty by seromuscular stripping and mucosal inversion facilitates early establishment of feeds in proximal jejunal atresia.
Microtubules at focal adhesions – a double-edged sword
Authors: Seetharaman Shailaja , Etienne-Manneville Sandrine
Published: October 2019

Cell adhesion to the extracellular matrix is essential for cellular processes, such as migration and invasion. In response to cues from the microenvironment, integrin-mediated adhesions alter cellular behaviour through cytoskeletal rearrangements. The tight association of the actin cytoskeleton with adhesive structures has been extensively studied, whereas the microtubule network in this context has gathered far less attention. In recent years, however, microtubules have emerged as key regulators of cell adhesion and migration through their participation in adhesion turnover and cellular signalling. In this Review, we focus on the interactions between microtubules and integrin-mediated adhesions, in particular, focal adhesions and podosomes. Starting with the association of microtubules with these adhesive structures, we describe the classical role of microtubules in vesicular trafficking, which is involved in the turnover of cell adhesions, before discussing how microtubules can also influence the actin–focal adhesion interplay through RhoGTPase signalling, thereby orchestrating a very crucial crosstalk between the cytoskeletal networks and adhesions.
Accuracy of multiparametric magnetic resonance imaging for detecting extracapsular extension in prostate cancer: a systematic review and meta-analysis
Authors: Zhang Fan , Liu Chen-Lu , Chen Qian , Shao Sheng-Chao , Chen Shuang-Qing
Published: October 2019

Objective:

To evaluate the diagnostic accuracy of multiparametric MRI (mpMRI) for detecting extracapsular extension (ECE) in patients with prostate cancer (PCa).

Methods and materials:

We searched MEDLINE, PubMed, Embase and the Cochrane library up to December 2018. We included studies that used mpMRI to differentiate ECE from organ-confined PCa with a combination of T  2 weighted imaging (T  2WI), diffusion-weighted imaging, and dynamic contrast-enhanced MRI. All studies included had pathological diagnosis with radical prostatectomy. Two reviewers independently assessed the methodological quality of included studies by using Quality Assessment of Diagnostic Accuracy Studies 2 tool. We calculated pooled sensitivity, specificity, positive and negative predictive values, diagnostic odds ratios and receiver operating characteristic curve for mpMRI from 2 × 2 tables.

Results:

A total of 17 studies that comprised 3374 participants were included. The pooled data showed a sensitivity of 0.55 (95% confidence interval 0.43, 0.66]) and specificity of 0.87 (95% confidence interval 0.82, 0.91) for extracapsular extension detection in PCa.

Conclusion:

First, our meta-analysis shows moderate sensitivity and high specificity for mpMRI to differentiate ECE from organ-confined prostate cancer before surgery. Second, our meta-analysis shows that mpMRI had no significant differences in performance compared with the former meta-analysis with use of T  2WI alone or with additional functional MRI.

Advances in knowledge:

It is the first meta-analysis to evaluate the accuracy of mpMRI in combination of TWI, diffusion-weightedimaging and dynamiccontrast-enhanced-MRI for extracapsular extension detection.
A Billion Years of History within the Grevena-Deskati Watershed
Authors: Ghikas Dina , Rassios Anne Ewing
Published: October 2019

The river system of West Macedonia comprises the headwaters and western extent of the Aliakmon watershed.  This region has a unique and highly complex geologic history (Rassios, 2008; Rassios, 2011), many aspects of which can be inferred by examining conglomerate (river-cobble) formations in the region.  These formations contain all rock types found within the modern-day river basin, as well as some which are not found within today's basin.  River-deposited sediments and cobbles found along today’s Aliakmon and Venetikos River systems trace the courses of ancient river flows, and thus provide information about past climatic conditions and tectonic events.  The sediments making up conglomerate formations in the region are mature, containing cobbles which have been transported, consolidated, eroded and redeposited up to five times (Rassios and Grivas, 1998).  This recycling of cobbles leaves only the most durable rocks while softer rocks are destroyed via abrasion.  Prehistoric peoples availed themselves of this concentrated and convenient selection of high-quality stones for the purpose of fashioning tools and weapons.
Assessing the development and implementation of the Global Trigger Tool method across a large health system in Sicily
Authors: Parrinello Vincenzo , Grasso Elena , Saglimbeni Giuseppe , Patanè Gabriella , Scalia Alma , Murolo Giuseppe , Lachman Peter
Published: October 2019

Background: The Institute for Healthcare Improvement (IHI) has proposed a new method, the Global Trigger Tool (IHI GTT), to detect and monitor adverse events (AEs) and provide information to implement improvement. In 2015, the Sicilian Health System adopted IHI GTT to assess the number, types and severity levels of AEs. The GTT was implemented in 44 of 73 Sicilian public hospitals and 18,008 clinical records (CRs) were examined. Here we present the standardized application of the GTT and the preliminary results of 14,706 reviews of CRs.

Methods: IHI GTT was adapted, developed and implemented to the local context. Reviews of CRs were conducted by 199 professionals divided into 71 review teams consisting of three individuals: two of whom had clinical knowledge and expertise, and a physician to authenticate the AE. The reviewers entered data into a dedicated IT-platform. All 44 of the public hospitals were included, with approximately 300,000 yearly inpatient admissions out of a population of approximately 5 million. In total, 14,706 randomized CRs of inpatients from medicine, surgery, obstetric and ICU wards, from June 2015 to June 2018 were reviewed.

Results: In 975 (6.6%) CRs at least one AE was found. Approximately 20,000 patients of the 300,000 discharged each year in Sicily have at least one AE. In 5,574 (37.9%) CRs at least one trigger was found. A total of 1,542 AEs were found. The analysis of ROC curve shows that the presence of two triggers in a CR indicates with high probability the presence of an AE. The most frequent type of AE was in-hospital related infection.

Conclusions: The GTT is an efficient method to identify AEs and to track improvement of care. The analysis and monitoring of some triggers is important to prevent AEs. However, it is a labor-intensive method, particularly if the CRs are paper-based.
Epitope mapping of an uncertain endogenous antigen implies secretogranin II peptide splicing
Authors: Howlett David R. , Clarke Iain J. , Newton Russell P. , Hart John E.
Published: October 2019

Background: The search for a tissue-mass reducing reproductive hormone involved a bioassay-guided physicochemical fractionation of sheep blood plasma. This brought forth a candidate protein whose apparent mass on gels and in mass spectrometry (MS) was 7-8 kDa, implying a polypeptide of ~70 residues. Four purification runs gave Edman N-terminal sequences relating to 1MKPLTGKVKEFNNI14. This is bioinformatically obscure and has been resistant to molecular biological investigation. The sequence was synthesized as the peptide EPL001, against which was raised a goat polyclonal antiserum, G530. Used in an antigen capture campaign, G530 pointed to the existence of a novel derivative of secretogranin II (SgII), the neuroendocrine secretory vesicle helper protein and prohormone. The proposed SgII derivative was dubbed SgII-70, yet the sequence commonality between SgII and EPL001 is essentially NNI.

Methods: Immunohistochemical (IHC) labelling with G530 is reported within rat, mouse and human cerebrovasculature and in glandular elements of the mouse intestine. Epitope mapping involved IHC peptide preabsorption, allied to deductive bioinformatics and molecular modelling in silico.

Results: G530 is deemed monoepitopic in regard to both its synthetic antigen (EPL001) and its putative endogenous antigen (SgII related). The epitope within EPL001 of the anti-EPL001 antibody is inferred to be the contiguous C-terminal 9KEFNNI14. This is so because the G530 blockade data are consistent with the epitope in the mammalian endogenous antigen being part contiguous, part non-contiguous KE·F·NNI, ex hypothesi. The observed immunostaining is deduced to be due to pre-SgII-70, which has a non-C-terminal NNI, and SgII-70, which has an N-terminal MLKTGEKPV/N and a C-terminal NNI (these two motifs being in the reverse order in the SgII parent protein).

Conclusion: The present data are consistent with the hypothesis that the anti-EPL001 antibody binds to an SgII-related epitope. SgII is apparently subject to peptide splicing, as has been reported for the related chromogranin A.
Diversity of desmid algae (Charophyta: Conjugatophyceae) in the vicinity of Yugorsk city (KMAO-Yugra, Russia)
Authors: Shakhmatov Andrei S. , Pavlovskiy Evgeniy V.
Published: October 2019

The article provides an annotated list, which contains 35 species and subspecific taxa of desmid algae collected in 2015 in swamps near Yugorsk city, West Siberia. Twelve species (Closterium costatum, Cosmarium regnesi, Euastrum ansatum, E. gayanum, E. pulchellum, Staurastrum aculeatum, S. arcuatum var. subavicula, S. tohopekaligense, Staurodesmus dickiei var. circularis, S. glaber, Xanthidium cristatum, X. uncinatum) and one variety (Closterium closterioides var. intermedium) are new for the Khanty-Mansi Autonomous Okrug. Data on morphology and distribution of the species are provided.
DA FUNÇÃO SOCIAL À FUNÇÃO ECONÔMICA DA TERRA: impactos da Lei nº 13.465/17 sobre as políticas de regularização fundiária e o direito à cidade no brasil.
Authors: Alfonsin Betânia De Moraes , Pereira Pedro Prazeres Fraga , Lopes Débora Carina , Rocha Marco Antônio , Boll Helena Corrêa
Published: October 2019

O artigo analisa o novo modelo de Regularização Fundiária Urbana adotado pela Lei 13.465/17, demonstrando a ruptura paradigmática ocorrida em relação ao paradigma anterior consagrado pelo Estatuto da Cidade. A passagem de um modelo que priorizava o direito à cidade e a função social da propriedade para outro que privilegia a mera titulação e a função econômica da terra é desvelada a partir da análise comparativa de vários dispositivos legais. A pesquisa, realizada utilizando o método dialético, conclui que o Brasil, com tal alteração no marco legal da terra,  insere-se em um movimento internacional de financeirização da moradia, impondo uma derrota ao direito à cidade no primeiro país do mundo que o positivou em sua ordem jurídico-urbanística.
Palliative radiotherapy: what do nurses know?
Authors: Hayden Kim , Connolly Michael
Published: October 2019

Background:

palliative radiotherapy can improve quality of life for patients who are symptomatic of advanced cancers. However, this treatment modality is underused and is often mistimed, which negates its potential benefit.

Aim:

the aim of this study was to assess nursing knowledge of palliative radiotherapy in the context of caring for patients with a cancer diagnosis.

Methods:

a quantitative method of research was employed using a questionnaire to assess palliative radiotherapy knowledge among a purposive sample of 162 oncology and palliative care nurses.

Findings:

the response rate was 48.14%. More than half of respondents reported their knowledge of radiotherapy as insufficient for their practice and almost all agreed they would benefit from more education.

Conclusion:

nurses require more training to identify when palliative radiotherapy would be an effective symptom control option; specific areas of focus for developing future radiotherapy educational programmes are highlighted.
Skin Prick Test Reactivity to Common Aeroallergens among Allergic Rhinitis Patients in Jordan
Authors: M Al-Shagahin Hani , F Kharboush Ibrahim , Al-Zayadneh Enas , Alharazneh Abdelrahman , Albataineh Eman , Alqatamin Ala
Published: October 2019

The distribution and pattern of aeroallergens are significantly different between different countries and even in the different parts of the same country. The present study aims to evaluate the most common aeroallergens among allergic rhinitis patients in the city of Al-Karak, Jordan. A cross-sectional study was conducted at Department of Otorhinolaryngology, Mutah University, from March 2016-April 2018. Patients with a clinical diagnosis of allergic rhinitis were enrolled and Skin Prick Test (SPT) was performed using 11 common aeroallergens including, grass, weed, tree, mite, and mould in 140 patients. The results showed that the overall rate of sensitization to any allergen was 85.7%. It was shown that 69.3% of patients were poly-sensitized; while, 16.4% were sensitized to only one allergen. The majority of the common allergens were Olive tree pollen (51.4%), Dermatophagoides pteronyssinus (37.9%), respectively. Mould (Alternaria) was the least prevalent allergen (17.1%). The present study has shown the importance of Olive tree pollen which, is widely cultivated in Al-Karak, Jordan. The diagnosis of pollen allergen can be simplified by using a combination of a few common allergens.
Innate Immunity Signatures of Early Childhood Caries (ECC) and Severe Early Childhood Caries
Authors: Yuni Astuti Eko Sri , Made Sukrama I Dewa , Nova Mahendra Agung
Published: October 2019

Caries that affects children under the age of 6 is known as early childhood caries (ECC). According to the American Academy of Pediatric Dentistry (AAPD), ECC is defined as the presence of one or more teeth with caries (cavities or no cavities), missing teeth due to caries or the presence of restoration deciduous teeth in children under 71 months. If it occurred on the smooth surface of the tooth in children under 3 years of age, the disease is classified as severe early childhood caries (S-ECC). Streptococcus mutans plays important role in the etiology of caries of preschool children, which is a contagious pathological entity. The pathogen is an acidogenic and aciduric bacteria. The occurrence of caries is a complex process of interaction between host factors (teeth), microorganisms, substrates (carbohydrates) and the environment, including saliva. This mini review aims to summarize current findings on several markers of innate immune system related to ECC and S-ECC namely lysozyme, salivary lactoferrin, IL-8, CD36 of salivary neutrophils, and sCD14
Cardiotropic activity of estrogens during hormone replacement therapy in postmenopausal women
Authors: Karachentsev A. N. , Kukes V. G. , Kisrieva A. S. , Mazerkina E. A.
Published: October 2019

Cardiotropic activity of estrogens after a single administration and during 12-week substitute hormone therapy was studied during echocardiography and Doppler echocardiography in estrogen deficient women with natural or surgical postmenopause with negative cardiovascular (vasomotor) symptoms with hyperkinetic central hemodynamics, high arterial pressure, and disordered diastolic function of the left ventricle. The results confirm the cardioprotective and positive hemodynamic activity of substitute estrogens. Estrogens improved the initially disturbed diastolic and systolic function of the left ventricle, moderately decreased heart rate and systolic and diastolic arterial pressure. Time course of cardioprotective and hemodynamic effects of substitute monoestrogen therapy and estrogen/gestagen hormone therapy was virtually the same.
Diabetes mellitus incidence and prevalence in Moscow
Authors: Kuraeva T. L. , Sergeev A. S. , Lebedev N. B. , Babadzhanova G. Yu. , Kerimi N. B.
Published: October 2019

Epidemiologic survey of two diabetes mellitus types in Moscow has shown that the incidence of type I diabetes markedly increases from birth (0.012-0.013%) to the age of 10-14 (0.04-0.045 %), after which somewhat reduces (0.02-0.03 %) and thus persists up to 40. Type I diabetes prevalence increases from 0.002-0.004 % at the age of 0 to 4 years to 0.14-0.092 % by the age of 35-39 in men and women, respectively. Type II diabetes is diagnosed after the age of 20. At the age of 20 to 24 this diabetes incidence is lower than that of type I condition; at the age of 25-34 the incidence of both is approximately the same, and after 35 the incidence of type II is much higher than that of type I diabetes. Type II diabetes prevalence by the age of 40 is 0.074 and 0.122% in men and women, respectively. Prevalence of diabetes cases treated with diets and oral sugar-reducing drugs at the age 75 and older is 4.3 % in men and 5.5 % in women, of insulin- treated cases 1.2 and 0.5 %, respectively. The true prevalence of type II diabetes is however higher and that of type I condition lower than the resultant values; this is explained by a frequent prescription of insulin to elderly patients with type II diabetes because of complications or concomitant diseases.