bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation of T cells from adult human hematopoietic stem cells and progenitors in a fetal thymic organ culture system: stimulation by tumor necrosis factor-α
Authors: Weekx Steven F. A. , Snoeck Hans W. , Offner Fritz , De Smedt Magda , Van Bockstaele Dirk R. , Nijs Griet , Lenjou Marc , Moulijn Adriaan , Rodrigus Inez , Berneman Zwi N. , Plum Jean
Published: October 2019

To investigate the T-lymphopoietic capacity of human adult bone marrow (ABM) hematopoietic progenitor cells, CD34+Lin−, CD34+CD38+, and CD34++CD38− cells were cultured in a severe combined immunodeficient (SCID) mouse fetal thymic organ culture (FTOC). Direct seeding of these progenitors resulted in a moderate to severe cell loss, particularly for the CD34++CD38− cell fraction, and T cells could only be generated from the CD34+Lin− fraction. Preincubation for 36 hours with interleukin-3 (IL-3) and stem cell factor (SCF) led to an improved cell survival and proliferation, although T-cell development was seen only in the CD34+Lin− fraction. Addition of tumor necrosis factor (TNF)- to IL-3 + SCF-supplemented preincubation medium resulted in optimal cell survival, cell proliferation. and T-cell generation of all 3 cell fractions. The TNF- effect resulted in an up-regulation of CD127 (ie, the IL-7 receptor -chain) in a small subset of the CD34+ cells. No evidence could be generated to support the possibility that TNF- inhibits a cell population that suppresses T-cell differentiation. A quantitatively different T-cell generation potency was still seen between the 3 subpopulations: CD34+Lin− (100% success rate) > CD34+CD38+ (66%) > CD34++CD38− (25%). These data contrast with our previous findings using fetal liver and cord blood progenitors, which readily differentiate into T-lymphocytes in FTOC, even without prestimulation with cytokines. Our results demonstrate that adult CD34++CD38− cells, known to contain hematopoietic stem cells, can differentiate into T-lymphocytes and that a significant difference exists in T-lymphopoietic activity of stem cells derived from ontogenetically different sources.
Retinoic acid is a negative regulator for the differentiation of cord blood-derived human mast cell progenitors
Authors: Kinoshita Tatsuya , Koike Kenichi , Mwamtemi Hadija Hemed , Ito Susumu , Ishida Shuichi , Nakazawa Yozo , Kurokawa Yumi , Sakashita Kazuo , Higuchi Tsukasa , Takeuchi Kouichi , Sawai Nobukuni , Shiohara Masaaki , Kamijo Takehiko , Kawa Shigeyuki , Yamashita Tetsuji , Komiyama Atsushi
Published: October 2019

We examined the effects of retinoids on the human mast cell development using a serum-deprived culture system. When 10-week cultured mast cells derived from CD34+ cord blood cells were used as target cells, both all-trans retinoic acid (ATRA) and 9-cis RA inhibited the progeny generation under stimulation with stem cell factor (SCF) in a dose-dependent manner (the number of progeny grown by SCF plus RA at 10−7 mol/L was one tenth of the value obtained by SCF alone). The early steps in mast cell development appear to be less sensitive to RA according to the single CD34+c-kit+ cord blood cell culture study. The optimal concentration of RAs also reduced the histamine concentration in the cultured mast cells (3.00 ± 0.47 pg per cell in SCF alone, 1.44 ± 0.18 pg per cell in SCF+ATRA, and 1.41 ± 0.10 pg per cell in SCF+9-cis RA). RT-PCR analyses showed the expression of RAR, RARβ, RXR, and RXRβ messenger ribonucleic acid (mRNA) in 10-week cultured mast cells. The addition of an RAR-selective agonist at 10−10 mol/L to 10−7 mol/L decreased the number of mast cells grown in SCF, whereas an RXR-selective agonist at up to 10−8 mol/L was inactive. Among RAR subtype selective retinoids used at 10−9 mol/L to 10−7 mol/L, only the RAR agonist was equivalent to ATRA at 10−7 mol/L in its ability to inhibit mast cell growth. Conversely, the addition of excess concentrations of a RAR antagonist profoundly counteracted the retinoid-mediated suppressive effects. These results suggest that RA inhibits SCF-dependent differentiation of human mast cell progenitors through a specific receptor.
High-resolution Transmission Electron Microscopy Characterization of the Structure of Cu Precipitate in a Thermal-aged Multicomponent Steel
Authors: Han Lizhan , Liu Qingdong , Gu Jianfeng
Published: October 2019

High-dispersed nanoscale Cu precipitates often contribute to extremely high strength due to precipitation hardening, and whereas usually lead to degraded toughness for especially ferritic steels. Hence, it is important to understand the formation behaviors of the Cu precipitates. High-resolution transmission electron microscopy (TEM) is utilized to investigate the structure of Cu precipitates thermally formed in a high-strength low-alloy (HSLA) steel. The Cu precipitates were generally formed from solid solution and at the crystallographic defects such as martensite lath boundaries and dislocations. The Cu precipitates in the same aging condition have various structure of BCC, 9R and FCC, and the structural evolution does not greatly correlate with the actual sizes. The presence of different structures in an individual Cu precipitate is observed, which reflects the structural transformation occurring locally to relax the strain energy. The multiply additions in the steel possibly make the Cu precipitation more complex compared to the binary or the ternary Fe–Cu alloys with Ni or Mn additions. This research gives constructive suggestions on alloying design of Cu-bearing alloy steels.
Assessment of mercury pollution sources in beach sand and coastal soil by speciation analysis
Authors: Gallego José Luis R. , López-Antón Maria Antonia , de la Rosa Deva Martínez , Rodríguez-Valdés Eduardo , García-González Nerea , Rodríguez Elena , Martínez-Tarazona Maria Rosa
Published: October 2019

Background

An essential requisite for controlling and monitoring mercury in the environment is to identify its species in different types of soils and sediments, as this will help not only to establish its mobility in the environment and ecosystem and the degree of its toxicity, but also to establish the source of contamination. The objective of this work was to identify the origin of mercury in beach sands and soil taken from a coastal region with previously high mining and industrial activity by characterizing the mercury species using the technique known as thermal desorption (HgTPD).

Results

Apart from quartz, the main mineral species identified in the raw sands and soil were calcite, fluorite and barite. The concentration of mercury ranges from 5 to 23 µg g−1, and although it is distributed in different proportions in the function of the size, thermal desorption profiles demonstrated that the mercury species present in the samples do not vary with the mercury concentration and the particle size. By means of HgTPD, mercury oxide (HgO) was identified in the beach sands, whereas mercury sulfide (HgS) was found in the soil sample taken from the vicinity of the beach. Complementary methodologies foster the HgTPD conclusions and verify that mercury is present mostly in insoluble stable (HgS) or low-mobility (HgO) forms in the samples studied. Analyses by ICP-MS after sequential extraction and HPLC separation of mercury species show that inorganic mercury is the predominant form in the samples.

Conclusions

The technique HgTPD is a very useful tool to ascertain the origin of mercury in contaminated beach sands and shoreline soils. In the particular area studied in this work, the species identified indicate that previous mining activity was the source of the mercury and rule out the possibility that contamination is derived from coal combustion activities ongoing in the region.
Quantifying mechanisms in neurodegenerative diseases (NDDs) using candidate mechanism perturbation amplitude (CMPA) algorithm
Authors: Karki Reagon , Kodamullil Alpha Tom , Hoyt Charles Tapley , Hofmann-Apitius Martin
Published: October 2019

Background

Literature derived knowledge assemblies have been used as an effective way of representing biological phenomenon and understanding disease etiology in systems biology. These include canonical pathway databases such as KEGG, Reactome and WikiPathways and disease specific network inventories such as causal biological networks database, PD map and NeuroMMSig. The represented knowledge in these resources delineates qualitative information focusing mainly on the causal relationships between biological entities. Genes, the major constituents of knowledge representations, tend to express differentially in different conditions such as cell types, brain regions and disease stages. A classical approach of interpreting a knowledge assembly is to explore gene expression patterns of the individual genes. However, an approach that enables quantification of the overall impact of differentially expressed genes in the corresponding network is still lacking.

Results

Using the concept of heat diffusion, we have devised an algorithm that is able to calculate the magnitude of regulation of a biological network using expression datasets. We have demonstrated that molecular mechanisms specific to Alzheimer (AD) and Parkinson Disease (PD) regulate with different intensities across spatial and temporal resolutions. Our approach depicts that the mitochondrial dysfunction in PD is severe in cortex and advanced stages of PD patients. Similarly, we have shown that the intensity of aggregation of neurofibrillary tangles (NFTs) in AD increases as the disease progresses. This finding is in concordance with previous studies that explain the burden of NFTs in stages of AD.

Conclusions

This study is one of the first attempts that enable quantification of mechanisms represented as biological networks. We have been able to quantify the magnitude of regulation of a biological network and illustrate that the magnitudes are different across spatial and temporal resolution.
Quantitative iTRAQ-based proteomic analysis of differentially expressed proteins in aging in human and monkey
Authors: Wang Hao , Zhu Xiaoqi , Shen Junyan , Zhao En-Feng , He Dajun , Shen Haitao , Liu Hailiang , Zhou Yongxin
Published: October 2019

Background

The underlying physiological mechanisms associated with aging are still complex and unclear. As a very important tissue of human body, the circulatory system also plays a very important role in the process of aging. In this study, we use the isobaric tags for relative and absolute quantification (iTRAQ) method to identify differentially expressed proteins in plasma for humans and monkeys between young and aged. Western blotting and behavioral experiment in mice were performed to validate the expression of the candidate protein.

Results

Between the young / the old humans and the young / the old monkeys 74 and 69 proteins were found to be differently expressed, respectively. For the human samples, these included 38 up-regulated proteins and 36 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05).For the monkey samples, 51 up-regulated proteins and 18 down-regulated proteins (a fold change ≥1.3 or ≤ 0.667, p value ≤0.05). KEGG pathway analysis revealed that phagosome, focal adhesion, ECM-receptor interaction and PI3K/AKT signaling pathway were the most common pathways involved in aging. We found only IGFBP4 protein that existed in up-regulated proteins in aged both for human and monkey. In addition, the differential expression of IGFBP4 was validated by western blot analysis and IGFBP4 treatment mimicked aging-related cognitive dysfunction in mice.

Conclusions

This first, the integrated proteomics for the plasma protein of human and monkey reveal one protein-IGFBP4, which was validated by western blotting and behavioral analysis can promote the process of aging. And, iTRAQ analysis showed that proteolytic systems, and inflammatory responses plays an important role in the process of aging. These findings provide a basis for better understanding of the underlying mechanisms involved in aging.
Enhanced IFN-γ, but not IL-2, response to Mycobacterium tuberculosis antigens in HIV/latent TB co-infected patients on long-term HAART
Authors: Desalegn Girmay , Tsegaye Aster , Gebreegziabiher Dawit , Aseffa Abraham , Howe Rawleigh
Published: October 2019

Background

HIV-infected individuals with latent TB infection are at increased risk of developing active TB. HAART greatly reduces the incidence rate of TB in HIV-infected patients and reconstitutesMycobacterium tuberculosis (M. tuberculosis)-specific immune response in the first 12 months of therapy. The durability of the anti-mycobacterial immune restoration after a year of HAART however remains less investigated.

Method

A cross-sectional study was conducted to evaluateM. tuberculosis-specific functional immune responses in HIV/latent TB co-infected patients who were on HAART for at least 1.5 up to 9 years as compared to HAART-naïve patients. Three-hundred sixteen HIV-infected patients without active TB were screened by tuberculin skin testing forM. tuberculosisinfection and peripheral blood mononuclear cells (PBMCs) were isolated from 61 HIV/latent TB co-infected patients (30 HAART-naïve and 31 HAART-treated). IFN-γ and IL-2 ELISPOT as well as CFSE cell proliferation assays were performed after stimulation withM. tuberculosisantigens PPD and ESAT-6.

Result

The median frequency of PPD and ESAT-6 specific IFN-γ secreting cells was significantly higher in the HAART-treated patients as compared to HAART-naïve patients,p = 0.0021 andp = 0.0081 respectively. However, there was no significant difference in the median frequency of IL-2 secreting cells responding to PPD (p = 0.5981) and ESAT-6 (p = 0.3943) antigens between HAART-naïve and-treated groups. Both IFN-γ and IL-2 responses were independent of CD4+T cell count regardless of the HAART status. Notably, the frequency of PPD and ESAT-6 specific IL-2 secreting cells was positively associated with CD4+T cell proliferation while inversely correlated with duration of HAART, raising the possibility thatM. tuberculosis-specific IL-2 response that promote the antigen-specific CD4+T cell proliferation diminish with time on antiretroviral therapy in HIV/latent TB co-infected patients.

Conclusion

This study shows an increasedM. tuberculosis-specific IFN-γ, but not IL-2, response in HIV/latent TB co-infected patients with long-term HAART, consistent with only partial immune restoration. Future studies should, therefore, be done to prospectively define the rate and extent to which functional immune responses toM. tuberculosisare restored after long-term HAART.
Uncompleted emergency department care and discharge against medical advice in patients with neurological complaints: a chart review
Authors: Hoyer Carolin , Stein Patrick , Alonso Angelika , Platten Michael , Szabo Kristina
Published: October 2019

Background

Uncompleted emergency department care and against-medical-advice discharge represent relevant medical problems with impact on patient safety and potential medicolegal and socioeconomic consequences. They may also indicate structural or procedural problems in the emergency department (ED) relating to patient management and flow. While patients with neurological complaints frequently leave the ED against medical advice or without being seen, no dedicated analysis of this group of patients aiming at the identification of characteristics associated with irregular ED discharge has been performed so far.

Methods

A chart review was performed of all patients with neurological complaints presenting to a German interdisciplinary emergency department between January and December 2017 for neurological evaluation. Demographics, mode of presentation, process times, presenting symptoms and diagnosis were recorded. Patients leaving against medical advice after an informed consent discussion and signing of documentation (DAMA) or leaving prematurely without notifying ED staff (PL) were compared to the total of patients who were admitted or discharged (non-DAMA/PL).

Results

Of all patients presenting with neurological symptoms or complaints, 3% left against medical advice and 2.2% left prematurely. DAMA/PL patients were younger (p < .001), and they were more frequently self-presenting (p < 0.001). Headaches, seizures and sensory deficits were the most frequent presenting symptoms in DAMA/PL patients, and 56.1% of those presenting with a seizure had a history of epilepsy. The most common documented reason for leaving was the duration of door-to-doctor time.

Conclusions

Younger age, self-presenting mode of presentation and presentation with headache, seizures or sensory deficits are associated with premature leave or against-medical-advice discharge of patients with neurological complaints from the ED, and long waiting times were given as the major reason for leaving the ED. Increasing ED staff’s awareness of these factors and the optimization of pre-hospital assessment and demand management, thereby positively impacting on patient flow and ED process times, may help to prevent irregular discharges from the ED.
A prevalence survey of enteral parasites in preschool children in the Mangochi District of Malawi
Authors: Jones Timothy P. W. , Hart John D. , Kalua Khumbo , Bailey Robin L.
Published: October 2019

Background

Helminthic and protozoan infections are common, particularly in low- or middle-income countries. Although an association between parasite carriage and markers of poor growth have been shown in some studies, systematic reviews have suggested only a modest impact of clearing carriage. The prevalence of these pathogens and the effect that they have on growth in preschool children has never been investigated in Malawi.

Methods

One hundred ninety-three children aged 0–72 months were randomly recruited from rural villages in the Mangochi district of Malawi. Formol-ether concentration was performed on stool and the samples examined with a light microscope. Anthropometric data was taken for each child and the haemoglobin measured with a point of care test.

Results

The mean age of the children was 2 years 4 months. Overall prevalence of intestinal parasite infection was 37.3%. Protozoa were found in 28.5% of children, while helminths were found in 8.8%. The most commonly found organisms were Giardia lambia (12.4%), Entamoeba coli (10.4%) and Hookworm species (3.6%). Stunting was seen in 47.8% of children, 12.9% were underweight and 5.0% were wasted. No significant association was found between markers of poor growth and infection with any intestinal parasite.

Conclusions

We found that prevalence of helminth infection was low in preschool children living in the Mangochi district compared to international standards. However a significant proportion of the preschool population are infected with protozoa, particularly Giardia lambia. In this cohort, despite a significant prevalence of stunting, helminth infection was not significantly associated with any markers of poor growth. The significance of protozoal carriage and contribution to growth restriction in this context creates further avenues for future research.
Unexpected drug residuals in human milk in Ankara, capital of Turkey
Authors: Ergen Ayşe Meltem , Yalçın Sıddıka Songül
Published: October 2019

Background

Breast milk is a natural and unique nutrient for optimum growth and development of the newborn. The aim of this study was to investigate the presence of unpredictable drug residues in mothers’ milk and the relationship between drug residues and maternal-infant characteristics.

Methods

In a descriptive study, breastfed infants under 3 months of age and their mothers who applied for child health monitoring were enrolled for the study. Information forms were completed for maternal-infant characteristics, breastfeeding problems, crying and sleep characteristics of infants. Maternal and infant anthropometric measurements and maternal milk sample were taken. Edinburgh Postpartum Depression Scale was applied to mothers. RANDOX Infiniplex kit for milk was used for residual analysis.

Results

Overall, 90 volunteer mothers and their breastfed infants were taken into the study and the mean age of the mothers and their infants was 31.5 ± 4.2 years and 57.8 ± 18.1 days, respectively. Anti-inflammatory drug residues in breast milk were detected in 30.0% of mothers and all had tolfenamic acid. Overall, 94.4% had quinolone, 93.3% beta-lactam, 31.1% aminoglycoside and 13.3% polymycin residues. Drugs used during pregnancy or lactation period were not affected by the presence of residues. Edinburgh postpartum depression scores of mothers and crying and sleeping problems of infants were similar in cases with and without drug residues in breast milk. When controlling confounding factors, maternal body mass index alterations were detected to be significantly lower in mothers with anti-inflammatory drug residues in breast milk than in their counterparts (p = 0.017).

Conclusions

Our study suggests that there are unpredictable drug residues in the milk of many mothers. Anti-inflammatory drug exposure might affect maternal weight change during the postpartum period. Further studies are required to evaluate the impact of drug residues on maternal and infant health.
Maternal perceptions about caesarean section deliveries and their role in reducing perinatal and neonatal mortality in the Upper West Region of Ghana; a cross-sectional study
Authors: Naa Gandau Barnabas B. , Nuertey Benjamin D. , Seneadza Nana Ayegua Hagan , Akaateba Dominic , Azusong Emmanuel , Yirifere Judith Y. , Kankpeyeng Herta B. , Tette Edem M. A.
Published: October 2019

Background

Maternal perceptions about caesarean section contribute to delayed presentation of women for emergency obstetric care. This increases the risks of perinatal and neonatal mortality and slows down the reductions needed to achieve the sustainable development goal (SDG) target of reducing neonatal mortality and ending new-born deaths. The aim of the study is to determine maternal perceptions about caesarean section deliveries and their role in reducing neonatal mortality at a regional and a district hospital in the Upper West Region of Ghana.

Methods

This descriptive study was carried out at two hospitals in the Upper West Region, the most rural region in Ghana, between 15th January and 29th June, 2018. Maternal perceptions were examined among antenatal care attendants at the Upper West Regional Hospital (UWRH) and St Joseph’s Hospital Jirapa (SJH), a district hospital, using questionnaires administered by trained nurses.

Results

Altogether, 416 completed questionnaires were obtained, comprising 206 from expectant women attending the UWRH and 210 from SJH. Although the majority of women in this study preferred spontaneous vaginal delivery (87.4%, n = 348) to caesarean section, most of the respondents (n = 281, 73%) indicated their willingness to have a caesarean section if necessary. The main reason for not wanting a CS was the long recovery time (51.8%, n = 148). Almost half of women interviewed, representing 45.1% (180) did not know or feel that CS can promote child survival and about a fifth, 21.6% (85) believed that CS can have adverse effects on child survival. Factors associated with poor perception of CS included, no formal education, age less than 19 years and no employment.

Conclusion

Majority of women in this study had a positive attitude towards the uptake of CS if it becomes necessary. Lack of formal education, age less than 19 years and unemployment are associated with poor maternal perception of CS. Education to improve the perception of CS as a promoter of child survival is necessary and to discourage perceptions that it causes adverse perinatal or neonatal outcome particularly in at risk populations.
Allogeneic hematopoietic stem cell transplantation in two brothers with DNA ligase IV deficiency: a case report and review of the literature
Authors: Schober Sarah , Schilbach Karin , Doering Michaela , Cabanillas Stanchi Karin M. , Holzer Ursula , Kasteleiner Patrick , Schittenhelm Jens , Schaefer Juergen F. , Mueller Ingo , Lang Peter , Handgretinger Rupert
Published: October 2019

Background

DNA ligase IV deficiency is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV (LIG4) gene. DNA ligase IV is an essential protein for the development of a healthy immune system as well as for the protection of genomic integrity. Apart from typical stigmata, patients with DNA ligase IV deficiency are characterized by progressive bone marrow failure and a predisposition to malignancy. To our knowledge this reported case is the first description of two brothers with ligase IV deficiency who are treated with different hematopoietic stem cell transplantation (HSCT) regimens resulting in vastly divergent outcomes.

Case presentation

The cases of two brothers suffering from severe recurrent infections and growth retardation are described. The laboratory findings showed pancytopenia with significant lymphopenia. The two boys were diagnosed with DNA ligase IV deficiency, associated with severe combined immunodeficiency (SCID). Both patients received HSCT from two different matched unrelated donors (MUD) at the age of 33 and 18 months. The older brother succumbed post-transplant due to fatal side-effects 143 days after allogeneic HSCT. The younger brother – conditioned with a different regimen – received a T cell depleted graft 4 months later. No severe side-effects occurred, neither post-transplant nor in the following years. Ten years after HSCT the patient is well off, living a normal life and attending a regular high school. His immune system is fully reconstituted, resulting in a maximum of T cell receptor (TCR) diversity, which is a prerequisite for immune competence. However, he still suffers from microcephaly, dwarfism and dystrophy.

Conclusions

This case report gives an example of a successful HSCT as a treatment option in a genetic disorder such as ligase IV deficiency, using a rather mild conditioning regimen. Further studies are required to determine the viability and efficacy of this treatment option.
Open field study on the efficacy of fluralaner topical solution for long-term control of flea bite allergy dermatitis in client owned cats in Ile-de-France region
Authors: Briand Amaury , Cochet-Faivre Noelle , Prélaud Pascal , Armstrong Rob , Hubinois Céline
Published: October 2019

Background

Flea bite is considered to be the main cause of allergic dermatitis in cats. There is a need for treatments able to control clinical signs of allergic dermatitis associated with flea bite in cats.

This was an open pre-treatment versus post-treatment clinical field study. All cats included in the study presented pruritus, skin lesions or other evidence compatible with flea infestation. Skin lesions were assessed (using SCORFAD) at days 0, 28, 56 and 84 whereas pruritus severity was assessed (using PVAS) at days 0, 15, 28, 56 and 84. On day 0, The fluralaner (280 mg/ml) product (Bravecto® spot-on for cats) was supplied in pipettes containing 0.4, 0.89 and 1.79 ml for cats of 1.2–2.8 kg, > 2.8–6.25 kg and > 6.25–12.5 kg body weight, respectively. The other animals living in the same household also received fluralaner. Based on cytological examination at day 0, oral amoxicillin and clavulanic acid was prescribed for 21 days if indicated. For cats presenting intense pruritus and discomfort at day 0, oral prednisolone at 0.5 mg/kg was prescribed for 3 days.

Results

During the study all cats, except for one (cat number 10), improved significantly. Post-treatment median SCORFAD scores at all evaluations were significantly different from the pre-treatment score on day 0 (P values < 0.002 for all three post treatment examination days) with a score reduction of 49% on day 28, 79% on day 56 and 87% on day 84. The PVAS score decreased significantly over the study period for all cats but one (cat number 10). Post-treatment median PVAS scores at all evaluations were significantly different from the pre-treatment PVAS score on day 0 (P value < 0.002 for all four post-treatment days) with a reduction of 46% on day 15, 67% on day 28, 82% on day 56 and 92% on day 84. No adverse reaction or other health issue was reported during the study.

Conclusions

A single topical treatment with fluralaner results in a significant reduction of flea bite allergic dermatitis clinical signs in cats over the subsequent 12 weeks without any additional environmental treatment.
Phenotyping diabetic cardiomyopathy in Europeans and South Asians
Authors: Paiman Elisabeth H. M. , van Eyk Huub J. , Bizino Maurice B. , Dekkers Ilona A. , de Heer Paul , Smit Johannes W. A. , Jazet Ingrid M. , Lamb Hildo J.
Published: October 2019

Background

The pathogenesis and cardiovascular impact of type 2 diabetes (T2D) may be different in South Asians compared with other ethnic groups. The phenotypic characterization of diabetic cardiomyopathy remains debated and little is known regarding differences in T2D-related cardiovascular remodeling across ethnicities. We aimed to characterize the differences in left ventricular (LV) diastolic and systolic function, LV structure, myocardial tissue characteristics and aortic stiffness between T2D patients and controls and to assess the differences in T2D-related cardiovascular remodeling between South Asians and Europeans.

Methods

T2D patients and controls of South Asian and European descent underwent 3 Tesla cardiovascular magnetic resonance imaging (CMR) and cardiac proton-magnetic resonance spectroscopy (1H-MRS). Differences in cardiovascular parameters between T2D patients and controls were examined using ANCOVA and were reported as mean (95% CI). Ethnic group comparisons in the association of T2D with cardiovascular remodeling were made by adding the interaction term between ethnicity and diabetes status to the model.

Results

A total of 131 individuals were included (54 South Asians [50.1 ± 8.7 years, 33% men, 33 patients vs. 21 controls) and 77 Europeans (58.8 ± 7.0 years, 56% men, 48 patients vs. 29 controls)]. The ratio of the transmitral early and late peak filling rate (E/A) was lower in T2D patients compared with controls, in South Asians [− 0.20 (− 0.36; − 0.03),P = 0.021] and Europeans [− 0.20 (− 0.36; − 0.04),P = 0.017], whereas global longitudinal strain and aortic pulse wave velocity were similar. South Asian T2D patients had a higher LV mass [+ 22 g (15; 30),P < 0.001] (Pfor interaction by ethnicity = 0.005) with a lower extracellular volume fraction [− 1.9% (− 3.4; − 0.4),P = 0.013] (Pfor interaction = 0.114), whilst European T2D patients had a higher myocardial triglyceride content [+ 0.59% (0.35; 0.84),P = 0.001] (Pfor interaction = 0.002) than their control group.

Conclusions

Diabetic cardiomyopathy was characterized by impaired LV diastolic function in South Asians and Europeans. Increased LV mass was solely observed among South Asian T2D patients, whereas differences in myocardial triglyceride content between T2D patients and controls were only present in the European cohort. The diabetic cardiomyopathy phenotype may differ between subsets of T2D patients, for example across ethnicities, and tailored strategies for T2D management may be required.
Differential secretome of pancreatic cancer cells in serum-containing conditioned medium reveals CCT8 as a new biomarker of pancreatic cancer invasion and metastasis
Authors: Liu Peng , Kong Lingming , Jin Haoyi , Wu Yunhao , Tan Xiaodong , Song Bing
Published: October 2019

Background

Pancreatic cancer is a malignancy with a very poor prognosis. The emergence of liquid biopsy is expected to achieve accurate early diagnosis through detection of tumor-derived secreted proteins in the blood. Early diagnosis and treatment of pancreatic cancer could help to improve prognosis.

Methods

The pretreatment approach of samples can have a major effect on downstream analysis. In this study, we used a pair of homologous pancreatic cancer cell supernatants with different capacities for invasion and metastasis to examine secreted proteins in the conditioned media without the removal of fetal bovine serum, namely through size exclusion chromatography combined with high-abundance protein affinity chromatography to enrich low-concentration protein, followed by mass spectrometry using triple dimethyl labeling. Identification of proteins was performed using an online public database and western blot.

Results

Mass spectrometry data revealed 77 proteins with quantitative properties, of which 12 proteins had over a 1.5-fold difference (in the supernatant of the highly invasive pancreatic cancer cell line PC-1.0, the expression of 8 proteins were increased and the expression of 4 proteins were decreased). Bioinformatics analysis results showed that CCT8, CTSL, SAA1, IGF2 are secreted via the exosome pathway. According to the literature, with the exception of CCT8, the other three proteins can be detected in blood samples of pancreatic cancer patients, and they can be used as prognostic markers. Western blot results were used to validate consistency with MS results.

Conclusion

This study found that CCT8 can be used as a liquid biopsy marker to assess the prognosis of pancreatic cancer patients.
Measurement and application of patient similarity in personalized predictive modeling based on electronic medical records
Authors: Wang Ni , Huang Yanqun , Liu Honglei , Fei Xiaolu , Wei Lan , Zhao Xiangkun , Chen Hui
Published: October 2019

Background

Conventional risk prediction techniques may not be the most suitable approach for personalized prediction for individual patients. Therefore, individualized predictive modeling based on similar patients has emerged. This study aimed to propose a comprehensive measurement of patient similarity using real-world electronic medical records data, and evaluate the effectiveness of the individualized prediction of a patient’s diabetes status based on the patient similarity.

Results

When using no more than 30% of the whole training sample, the personalized predictive models outperformed corresponding traditional models built on randomly selected training samples of the same size as the personalized models (P < 0.001 for all). With only the top 1000 (10%), 700 (7%) and 1400 (14%) similar samples, personalized random forest, k-nearest neighbor and logistic regression models reached the globally optimal performance with the area under the receiver-operating characteristic (ROC) curve of 0.90, 0.82 and 0.89, respectively.

Conclusions

The proposed patient similarity measurement was effective when developing personalized predictive models. The successful application of patient similarity in predicting a patient’s diabetes status provided useful references for diagnostic decision-making support by investigating the evidence on similar patients.
Liraglutide exhibits anti-inflammatory activity through the activation of the PKA/CREB pathway
Authors: Wang Li , Feng Linjie , Zhang Jingyu
Published: October 2019

Qihong Que and colleagues found that liraglutide exhibited anti-inflammatory activity through the activation of the PKA/CREB pathway in an OA rat model. We believe there was a flaw in this research. In their first experiment, the sacrifice time of the 10 rats in the control group has not been stated. And when the rats in the OA-1, OA-5, OA-10, OA-20 and OA-28 groups were sacrificed, they were in different weeks of age. If the rats in the control group were compared to the rats in the OA-1, OA-5, OA-10, OA-20 and OA-28 groups respectively, the results may be biased due to differences in the week age of the rats. We believe that addressing this issue could further increase the value of their study.
Reasons for nonuse of contraceptive methods by women with demand for contraception not satisfied: an assessment of low and middle-income countries using demographic and health surveys
Authors: Moreira Laísa Rodrigues , Ewerling Fernanda , Barros Aluisio J. D. , Silveira Mariangela Freitas
Published: October 2019

Background

Nonuse of contraceptive methods by women in need of contraception may impact their sexual and reproductive health. The aim of this study was to describe the reasons for nonuse of contraception among women with demand for contraception not satisfied in low and middle-income countries (considering both overall countries and various subgroups of women).

Methods

We used the latest Demographic and Health Survey data from 47 countries. A descriptive analysis of the reasons for nonuse of contraceptive methods was performed among sexually active women with demand for contraception not satisfied. The prevalence of each reported reason was also evaluated according to marital status, woman’s age and schooling, area of residence, wealth index, and parity. Wealth-related absolute inequality for each reason was also evaluated using the Slope Index of Inequality. A pro-rich inequality pattern means that the reason is more prevalent among the richest women while a pro-poor means the reason is more common among the poorest ones.

Results

On average, 40.9% of women in need of contraception were not using any contraceptive methods to avoid pregnancy. Overall, the most prevalent reasons for nonuse of contraceptives were “health concerns” and “infrequent sex,” but the prevalence of each reason varied substantially across countries. Nonuse due to “opposition from others” was higher among married than unmarried women; in turn, the prevalence of nonuse due to “lack of access” or “lack of knowledge” was about two times higher in rural areas than in urban areas. Women with less schooling more often reported nonuse due to “lack of access.” Pro-rich inequality was detected for reasons “health concerns,” “infrequent sex,” and “method-related”, while the reasons “other opposed,” “fatalistic,” “lack of access,” and “lack of knowledge” were linked to patterns of pro-poor inequality.

Conclusions

Family planning promotion policies must take into account the different reasons for the nonuse of contraceptive methods identified in each country as well as the contextual differences regarding women of reproductive age (such as social norms and barriers that prevent women from accessing and using contraceptives).
Hepatic PKA inhibition accelerates the lipid accumulation in liver
Authors: Yang Jining , Zhang Xiaoying , Yi Long , Yang Ling , Wang Wei Eric , Zeng Chunyu , Mi Mantian , Chen Xiongwen
Published: October 2019

Background/aims

Liver lipid accumulation induced by high-fat diet (HFD) is an early onset process of non-alcoholic fatty liver diseases (NAFLD). Protein kinase A (PKA) is known to be involved in hepatic lipid metabolism. However, the role of PKA in NAFLD has not been well tested in vivo due to the lack of optimal PKA deficient mouse model.

Methods

A novel PKA-specific inhibitor gene was conditionally overexpressed in mouse (PKAi mouse) liver using LoxP/Cre system. PKA activity in the liver extract was measured with a commercial assay kit. The PKAi and control mice of 8-week age, were subjected to HFD or chow diet (CD) for 2 months. Body weight, liver index, and triglyceride in the liver were measured. RNA sequencing was performed for the liver tissues and analyzed with Gene Ontology (GO) and pathway enrichment.

Results

PKAi-GFP protein was overexpressed in the liver and the PKA activation was significantly inhibited in the liver of PKAi mouse. When fed with CD, RNA sequencing revealed 56 up-regulated and 51 down-regulated genes in PKAi mice compared with control mice, which were mainly involved in lipid metabolism though no significant differences in the body weight, liver index, triglyceride accumulation were observed between PKAi and control mice. However, when fed with HFD for 2 months, the liver was enlarged more, and the accumulation of triglyceride in the liver was more severe in PKAi mice. When comparing the transcriptomes of CD-fed and HFD-fed control mice, GO enrichment showed that the genes down-regulated by HFD were mainly enriched in immune-related GO terms, and up-regulated genes were enriched in metabolism. When comparing the transcriptomes of CD-fed and HFD-fed PKAi mice, GO analysis showed that the down-regulated genes were enriched in metabolism, while the up-regulated genes were clustered in ER stress-related pathways. When comparing HFD-fed PKAi and HFD-fed control mice, the genes with lower expression level in PKAi mice were enriched in the lipoprotein synthesis, which might explain that more TG is accumulated in PKAi liver after HFD feeding.

Conclusions

Reduced PKA activity could be a factor promoting the TG accumulation in the liver and the development of NAFLD.
Unravelling functional neurology: does spinal manipulation have an effect on the brain? - a systematic literature review
Authors: Meyer Anne-Laure , Amorim Michel-Ange , Schubert Martin , Schweinhardt Petra , Leboeuf-Yde Charlotte
Published: October 2019

Background

A recent hypothesis purports that spinal manipulation may cause changes at a brain level. Functional Neurology, a mainly chiropractic approach, promotes the use of spinal manipulation to improve ‘brain function’ as if it were a proven construct. No systematic review has been performed to investigate how well founded this hypothesis is.

Objective

To investigate whether spinal manipulation has an effect on ‘brain function’ that is associated with any clinical benefits.

Method

In this systematic review, the literature was searched in PubMed, Embase, and PEDro (final search February 2018). We included randomized or non-randomized controlled studies, in which spinal manipulation was performed to any region of the spine, applied on either symptomatic or asymptomatic humans, and compared to a sham or to another type of control. The outcome measures had to be stated as direct or proxy markers of ‘brain function’. Articles were reviewed blindly by at least two reviewers, using a quality checklist designed for the specific needs of the review. Studies were classified as of ‘acceptable’, ‘medium’, or ‘low’ methodological quality. Results were reported in relation to (i) control intervention (sham, ‘inactive control’, or ‘another physical stimulus’) and (ii) study subjects (healthy, symptomatic, or with spinal pain” subjects/spinal pain”), taking into account the quality. Only results obtained from between-group or between-intervention comparisons were considered in the final analysis.

Results

Eighteen of 1514 articles were included. Studies were generally of ‘low’ or ‘medium’ methodological quality, most comparing spinal manipulation to a control other than a sham. Thirteen out of the 18 studies could be included in the final analysis. Transitory effects of different types of ‘brain function’ were reported in the three studies comparing spinal manipulation to sham (but of uncertain credibility), in “subclinical neck/spinal pain” subjects or in symptomatic subjects. None of these three studies, of ‘medium’ or ‘acceptable’ quality, investigated whether the neurophysiological effects reported were associated with clinical benefits. The remaining 10 studies, generally of ‘low’ or ‘medium’ quality, compared spinal manipulation to ‘inactive control’ or ‘another physical stimulus’ and similarly reported significant between-group differences but inconsistently.

Conclusion

The available evidence suggests that changes occur in ‘brain function’ in response to spinal manipulation but are inconsistent across and - sometimes - within studies. The clinical relevance of these changes is unknown. It is therefore premature to promote the use of spinal manipulation as a treatment to improve ‘brain function’.
Determining optimal needle size for decompression of tension pneumothorax in children – a CT-based study
Authors: Leonhard Georg , Overhoff Daniel , Wessel Lucas , Viergutz Tim , Rudolph Marcus , Schöler Michael , Haubenreisser Holger , Terboven Tom
Published: October 2019

Background

For neonates and children requiring decompression of tension pneumothorax, specific recommendations for the choice of needle type and size are missing. The aim of this retrospective study was to determine optimal length and diameter of needles for decompression of tension pneumothorax in paediatric patients.

Methods

Utilizing computed tomography, we determined optimal length and diameter of needles to enable successful decompression and at the same time minimize risk of injury to intrathoracic structures and the intercostal vessels and nerve. Preexisting computed tomography scans of the chest were reviewed in children aged 0, 5 and 10 years. Chest wall thickness and width of the intercostal space were measured at the 4th intercostal space at the anterior axillary line (AAL) on both sides of the thorax. In each age group, three needles different in bore and length were evaluated regarding sufficient length for decompression and risk of injury to intrathoracic organs and the intercostal vessels and nerve.

Results

197 CT-scans were reviewed, of which 58 were excluded, resulting in a study population of 139 children and 278 measurements. Width of the intercostal space was small at 4th ICS AAL (0 years: 0.44 ± 0.13 cm; 5 years: 0.78 ± 0.22 cm; 10 years: 1.12 ± 0.36 cm). The ratio of decompression failure to risk of injury at 4th ICS AAL was most favourable for a 22G/2.5 cm catheter in infants (Decompression failure: right: 2%, left: 4%, Risk of injury: right: 14%, left: 24%), a 22G/2.5 cm or a 20G/3.2 cm catheter in 5-year-old children (20G/3.2 cm: Decompression failure: right: 2.1%, left: 0%, Risk of injury: right: 2.1%, left: 17%) and a 18G/4.5 cm needle in 10-year-old children (Decompression failure: right: 9.5%, left: 9.5%, Risk of injury: right: 7.1%, left: 11.9%).

Conclusions

In children aged 0, 5 and 10 years presenting with a tension pneumothorax, we recommend 22G/2.5 cm, 20G/3.2 cm and 18G/4.5 cm needles, respectively, for acute decompression.
Correction to: Procalcitonin levels in candidemia versus bacteremia: a systematic review
Authors: Cortegiani Andrea , Misseri Giovanni , Ippolito Mariachiara , Bassetti Matteo , Giarratano Antonino , Martin-Loeches Ignacio , Einav Sharon
Published: October 2019

The author wish to note there are three imprecisions in the article [1].