Long‐Term Fine Motor Capability on the Staircase Test Correlates with the Absolute Number, but Not the Density, of DARPP‐Positive Neurons in the Caudate‐Putamen

Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood progenitor cells (PBPC) have successfully been used as stem cells for both autologous and allogeneic transplants. However, little is known concerning the absolute number and phenotype of primitive progenitors, such as long-term culture-initiating cells (LTC-IC) in mobilized PBPC. The aim of our study was to evaluate the capacity of G- CSF to mobilize LTC-IC in the PB of normal individuals and to evaluate the phenotypic and functional characteristics of G-CSF mobilized LTC- IC. G-CSF was administered to 29 healthy volunteers at 7.5 micrograms or 10 micrograms/kg/d subcutaneously (SC) for 5 consecutive days and PBPC were harvested on day 6. Mobilization with G-CSF increased the absolute number of week 5 LTC-IC in PB 60-fold, while the number of CD34+ cells and committed colony forming cells (CFC) was increased sevenfold to 12-fold. The frequency of CFC and week 5 LTC-IC in CD34+ cells selected by fluorescence-activated cell sorter (FACS) from mobilized PBPC was 2 +/- 0.3-fold and 9 +/- 2.2-fold higher respectively than in CD34+ cells selected from unmobilized PBMNC. CFC were enriched in the CD34+ CD38+ and CD34+ HLA-DR+ populations. The absolute number of LTC-IC present in CD34+ CD38- and CD34+ HLA-DR- cells selected by FACS from either mobilized PBPC, unmobilized PBMNC or steady state bone marrow (BM) was similar (0.5% to 2%). In contrast to unmobilized PBMNC or steady state BM CD34+ CD38+ and CD34+ HLA-DR+ cells, which contain less than 0.1% LTC-IC, CD34+ CD38+ and CD34+ HLA- DR+ cells sorted from mobilized PBPC contained 0.5% to 5% of cells capable of sustaining hematopoiesis in long-term cultures for 5 weeks. However, 90% to 95% of LTC-IC present in mobilized CD34+ CD38+ and CD34+ HLA-DR+ cells were not able to sustain hematopoiesis for 8 weeks, while 30% of CD34+ CD38- and CD34+ HLA-DR- LTC-IC present in mobilized PBPC could sustain hematopoiesis for at least 8 weeks. This suggests that the majority of CD34+ CD38+ and CD34+ HLA-DR+ week 5 LTC-IC represent progenitors at an intermediate state of differentiation. We conclude that G-CSF effectively mobilizes LTC-IC in the blood of normal individuals. Although a fraction of these cells has functional characteristics similar to those of steady state PBMNC or BM LTC-IC, more than 85% of mobilized PBPC LTC-IC are CD34+ CD38+ and CD34+ HLA- DR+, capable of sustaining hematopoiesis for 5 weeks, but not for 8 weeks. The functional and phenotypic characterization of primitive and more mature populations of LTC-IC in mobilized PBPC should prove extremely useful in future studies examining the role of these progenitors in engraftment following transplantation.

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Nursing of prematurely born children: indicators of the effectiveness

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2021-66-3-102-109 ◽

2021 ◽

Vol 66 (3) ◽

pp. 102-109

Author(s):

T. V. Gnedko

Keyword(s):

Body Weight ◽

Health Status ◽

Premature Infants ◽

Maximum Level ◽

Perinatal Period ◽

Absolute Number ◽

Premature Babies ◽

The Absolute ◽

The Republic

The study and monitoring of international indicators of the health status of premature infants is the current vector of scientific research in neonatology.Objective. To assess the effectiveness of the nursing technologies of premature babies in the Republic of Belarus based on the analysis of long-term indicators of morbidity, mortality and survival of the infants with extremely low body weight.Material and methods. Statistical reports data were used for a retrospective analysis of epidemiological indicators for the period of 2002–2018.Results. The proportion of premature infants in the Republic of Belarus was stabilized at 4,2–4,5% increase in the absolute numbers, including those born weighing less than 1500 g. The ratio of the absolute number of alive and stillborn infants with extremely low body weight is many times higher than the initial values (p<0,05). The survival rate of infants with a body weight of 500–999g up to 1 year increased 2 times to the maximum level in 2018 (81,5%). There was an increase in the overall incidence of premature children in 2002–2010 (p<0,05) and a decrease by 2016 (p=0,001), including those born with a body weight of 500–999 g. Respiratory distress syndrome, intrauterine hypoxia and asphyxia during childbirth, an increase in the frequency of infections specific to the perinatal period (p <0,05) were registered more often. Among the children born with a body weight of 500–999 g, the incidence of congenital pneumonia for the period 2002–2009 increased to a maximum level of 263,4 ‰ (p <0,05) with a twofold decrease by 2018. The republican mortality rate of premature babies was stabilized at the level of 0,95 ‰ in the last 9 years, while the indicator was decreased 5 times among children weighing 500–999 g.Conclusion. The assessment of the long-term dynamics of the main indicators of the health status of premature infants in the Republic of Belarus testified to the effectiveness of a complex of organizational and medical measures for their nursing.

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The Issue of Sustainability in Third World Food Production (The Distinguishedl Lecture)

The Pakistan Development Review ◽

10.30541/v31i4ipp.511-534 ◽

1992 ◽

Vol 31 (4I) ◽

pp. 511-534

Author(s):

Winfried Von Urff

Keyword(s):

Developing Countries ◽

Population Growth ◽

Food Production ◽

Third World ◽

Total Population ◽

Absolute Number ◽

Comprehensive Analysis ◽

World Food ◽

The Absolute ◽

The Difference

In spite of the fact that food production in developing countries doubled over the last 25 years undernutrition is still widely spread. At the beginning of the eighties, according to FAO, 335 to 494 million people in developing countries suffered from serious undernutrition the difference being due to different concepts to determine undernutrition on which scientist were unable to find a consensus.) Unfortunately there is no recent comprehensive analysis of the food situation comparable to those of previous World Food Surveys but it can be taken for sure that the absolute number of undernourished has increased. According to unofficial FAO sources a figure of 870 million was estimated for 1990 (22 percent of the total population in developing countries) using the same concept that led to the figure of 494 million in 1979-81 (23 percent of the total population in developing countries) which means that most probably the number of undernourished increased at a rate slightly less than population growth.

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Skeletal and cardiac muscle protein turnover during cold acclimation in young rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.2000.278.3.r705 ◽

2000 ◽

Vol 278 (3) ◽

pp. R705-R711 ◽

Cited By ~ 8

Author(s):

T. A. McAllister ◽

J. R. Thompson ◽

S. E. Samuels

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Cardiac Muscle ◽

Cold Acclimation ◽

Protein Turnover ◽

Muscle Protein ◽

Muscle Protein Turnover ◽

Protein Mass ◽

The Absolute

The effect of long-term cold exposure on skeletal and cardiac muscle protein turnover was investigated in young growing animals. Two groups of 36 male 28-day-old rats were maintained at either 5°C (cold) or 25°C (control). Rates of protein synthesis and degradation were measured in vivo on days 5, 10, 15, and 20. Protein mass by day 20 was ∼28% lower in skeletal muscle (gastrocnemius and soleus) and ∼24% higher in heart in cold compared with control rats ( P < 0.05). In skeletal muscle, the fractional rates of protein synthesis ( k syn) and degradation ( k deg) were not significantly different between cold and control rats, although k syn was lower (approximately −26%) in cold rats on day 5; consequent to the lower protein mass, the absolute rates of protein synthesis (approximately −21%; P < 0.05) and degradation (approximately −13%; P < 0.1) were lower in cold compared with control rats. In heart, overall, k syn(approximately +12%; P < 0.1) and k deg(approximately +22%; P < 0.05) were higher in cold compared with control rats; consequently, the absolute rates of synthesis (approximately +44%) and degradation (approximately +54%) were higher in cold compared with control rats ( P < 0.05). Plasma triiodothyronine concentration was higher ( P < 0.05) in cold compared with control rats. These data indicate that long-term cold acclimation in skeletal muscle is associated with the establishment of a new homeostasis in protein turnover with decreased protein mass and normal fractional rates of protein turnover. In heart, unlike skeletal muscle, rates of protein turnover did not appear to immediately return to normal as increased rates of protein turnover were observed beyond day 5. These data also indicate that increased rates of protein turnover in skeletal muscle are unlikely to contribute to increased metabolic heat production during cold acclimation.

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AB0588 INFECTION AGGRAVATED DECREASE OF THE LEVEL OF TH17 AND TREG CELLS AND LOW-DOSE IL-2 REBALANCED TH17/TREG IN THE PERIPHERAL BLOOD OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5255 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1591.3-1591

Author(s):

Y. Liang ◽

H. Y. Wen ◽

Y. Duan ◽

Y. Liu ◽

Z. Yu ◽

...

Keyword(s):

T Cells ◽

Low Dose ◽

Lymphocyte Subsets ◽

Absolute Number ◽

Treg Cells ◽

Idiopathic Inflammatory Myopathies ◽

Inflammatory Myopathies ◽

Infection Group ◽

The Absolute ◽

Organ Infection

Background:Idiopathic inflammatory myopathies (IIM) are featured by a series of clinical presentation such as proximal muscle weakness, increased serum levels of creatine kinase and other muscle enzymes and involvement of other organs and systems[1, 2], which results in high morbidity and early mortality[3]. We have known the changes of the level of Th17 and Treg cells in IIM in previous studies[4-6]. However, whether infection affects lymphocyte subsets or not and whether the effect of low-dose interleukin-2 (IL-2) can be influenced by the use of immunosuppressants or not are still unclear.Objectives:The study aimed to explore the changes of lymphocyte subsets in patients of IIM with or without important organ infection, and the restoration of Th17/Treg after receiving low-dose IL-2.Methods:A total of 118 IIM patients were enrolled and classified into infection group and non-infection group based on the important organ infection. Of them, 48 cases were treated with low dose IL-2 (5.0*105IU for 5 days). The absolute number of peripheral total T, B, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cell subsets were analyzed by flow cytometry combined with absolute counting beads. Clinical data, laboratory examinations and the levels of peripheral lymphocyte subsets were analyzed retrospectively.Results:In these patients, especially in the infection group, the absolute number of T, CD4+T, CD8+T, NK, Th1, Th2, Th17 and Treg cells were significantly decreased as compared with that in the healthy controls, which were significantly increased by low dose IL-2 (especially Treg cells) treatment. The levels of ESR, LDH and HBDH and the ratio of Th17/Treg were significantly lower than those before IL-2 treatment (Z=-2.237, -2.083, -2.140, -3.663,P=0.025, 0.037, 0.032, 0.000). The 48 cases who received IL-2 treatment were divided into 2 groups according to whether they used immunosuppressants. There was no significant difference in the absolute number of T, B, CD4+T, CD8+T, Th1, Th2, Th17 and Treg cells, the proportion of Th17 and Treg cells and the ratio of Th17/Treg between the 2 groups (P>0.05).Conclusion:Global decrease in lymphocyte subsets was found in IIM patients, especially those who had important organ infection. A significant re-balance of Th17/Treg was observed after receiving treatment with low-dose IL-2. Furthermore, the restoration of lymphocyte subsets showed similar degree after treatment with or without immunosuppressants. Low-dose IL-2 may become a potential therapy for IIM patients. The mechanism of lymphocyte decrease in IIM is required further to study.References:[1]Clark K E N, Isenberg D A. A review of inflammatory idiopathic myopathy focusing on polymyositis[J]. European Journal of Neurology, 2017.[2]Tieu J, Lundberg IE, Limaye V. Idiopathic inflammatory myositis. Best Pract Res Clin Rheumatol. 2016. 30(1): 149-68.[3]Mandel DE, Malemud CJ, Askari AD. Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis. Int J Mol Sci. 2017. 18(5).[4]Zhang SX, Wang J, Sun HH, et al. Circulating regulatory T cells were absolutely decreased in dermatomyositis/polymyositis patients and restored by low-dose IL-2. Ann Rheum Dis. 2019 .[5]Espinosa-Ortega F, Gómez-Martin D, Santana-De Anda K, Romo-Tena J, Villaseñor-Ovies P, Alcocer-Varela J. Quantitative T cell subsets profile in peripheral blood from patients with idiopathic inflammatory myopathies: tilting the balance towards proinflammatory and pro-apoptotic subsets. Clin Exp Immunol. 2015. 179(3): 520-8.[6]Feng M, Guo H, Zhang C, et al. Absolute reduction of regulatory T cells and regulatory effect of short-term and low-dose IL-2 in polymyositis or dermatomyositis. Int Immunopharmacol. 2019. 77: 105912.Acknowledgments:Thanks for the support of my teachers, classmates and my family.Disclosure of Interests:None declared

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Altered mRNA Levels of Stress-Related Peptides in Mouse Hippocampus and Caudate-Putamen in Withdrawal after Long-Term Intermittent Exposure to Tobacco Smoke or Electronic Cigarette Vapour

International Journal of Molecular Sciences ◽

10.3390/ijms22020599 ◽

2021 ◽

Vol 22 (2) ◽

pp. 599

Author(s):

Lucia Carboni ◽

Luisa Ponzoni ◽

Daniela Braida ◽

Mariaelvina Sala ◽

Cecilia Gotti ◽

...

Keyword(s):

Public Health Problem ◽

Mrna Levels ◽

Obsessive Compulsive ◽

Bdnf Mrna ◽

Object Recognition Test ◽

Caudate Putamen ◽

Molecular Alterations ◽

Marble Burying ◽

Cigarette Withdrawal

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive–compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.

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The Impact of Age and Gender on Hematopoietic Stem Cells and Immune Contexture of the Bone Marrow Microenvironment

Cells Tissues Organs ◽

10.1159/000510774 ◽

2020 ◽

pp. 1-6

Author(s):

Rebar N. Mohammed

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Hematopoietic Stem Cells ◽

Immune Cells ◽

Absolute Number ◽

Cell Number ◽

Hematopoietic Stem ◽

The Absolute ◽

And Gender ◽

The Impact

Hematopoietic stem cells (HSCs) are a rare population of cells that reside mainly in the bone marrow and are capable of generating and fulfilling the entire hematopoietic system upon differentiation. Thirty-six healthy donors, attending the HSCT center to donate their bone marrow, were categorized according to their age into child (0–12 years), adolescence (13–18 years), and adult (19–59 years) groups, and gender into male and female groups. Then, the absolute number of HSCs and mature immune cells in their harvested bone marrow was investigated. Here, we report that the absolute cell number can vary considerably based on the age of the healthy donor, and the number of both HSCs and immune cells declines with advancing age. The gender of the donor (male or female) did not have any impact on the number of the HSCs and immune cells in the bone marrow. In conclusion, since the number of HSCs plays a pivotal role in the clinical outcome of allogeneic HSC transplantations, identifying a younger donor regardless the gender is critical.

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Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern Radiation Doses to the Lungs and Heart and From Previous Randomized Trials

Journal of Clinical Oncology ◽

10.1200/jco.2016.72.0722 ◽

2017 ◽

Vol 35 (15) ◽

pp. 1641-1649 ◽

Cited By ~ 227

Author(s):

Carolyn Taylor ◽

Candace Correa ◽

Frances K. Duane ◽

Marianne C. Aznar ◽

Stewart J. Anderson ◽

...

Keyword(s):

Breast Cancer ◽

Lung Cancer ◽

Cardiac Mortality ◽

Cancer Radiotherapy ◽

Breast Cancer Radiotherapy ◽

The Absolute ◽

Whole Heart ◽

Meta Analyses ◽

Modern Radiotherapy

Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage points in suitable women but can cause a second cancer or heart disease decades later. We estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a systematic literature review was performed of lung and heart doses in breast cancer regimens published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence ≥ 10 years after radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating 0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95% CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04 (95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on mortality, but smoking cessation substantially reduces radiotherapy risk.

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Determination of the Absolute Number of Transgene Copies in CMVFUT Transgenic Pigs

Annals of Animal Science ◽

10.2478/v10220-012-0029-z ◽

2012 ◽

Vol 12 (3) ◽

pp. 349-356 ◽

Cited By ~ 4

Author(s):

Daniel Lipiński ◽

Joanna Zeyland ◽

Andrzej Pławski ◽

Ryszard Słomski

Keyword(s):

Copy Number ◽

Transgenic Animals ◽

Promoter Sequence ◽

Absolute Number ◽

Transgenic Pigs ◽

Cmv Promoter ◽

Genetic Construct ◽

Coding Sequence ◽

The Absolute

Determination of the Absolute Number of Transgene Copies in CMVFUT Transgenic PigsThe aim of this research was to determine the number of transgene copies in the DNA of transgenic pigs. The copy number of the transgene was analysed in the transgenic animals with introduced pCMVFUT genetic construct containing a coding sequence of human H transferase under a control of CMV promoter. The copy number of the transgene that had integrated with the genome of the transgenic animals was analysed by qPCR with SYBR Green dye, which enabled nonspecific double-stranded DNA detection. CMVFT-2F and CMVFT-2R primers were used to amplify a 149 bp fragment of DNA. Forward primer had a sequence complementary to a promoter sequence and reverse primer to a coding sequence of H transferase. The copy number of the transgene in the examined samples was established by plotting the CT values obtained on a standard curve, which had been set by the usage of the CT values for the successive standard dilutions with known copy number (1.438-1.431 copies). As a standard we used pCMVFut genetic construct hydrolyzed with Not I restriction enzyme to a linear form. The real-time PCR results helped to establish the range of 3 - 4 as the number of the transgene copies that had integrated to the swine genome.

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