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The kainic acid-induced seizure mouse model is widely used in epilepsy research. In this study, we applied kainic acid to the subcutaneous injections of three different sources of DBA/2 mice to compare and evaluate the seizure response. The three mouse sources consisted of DBA/2Kor1 (Korea FDA source), DBA/2A (USA source), and DBA/2 (Japan source), and were purchased from different vendors. To compare the responses of DBA/2 mice to kainic acid injections, we examined the survival rate, seizure phenotype scoring, and behavioral changes. We also evaluated brain lesions using histopathological analysis. Following the administration of kainic acid, almost half of the cohort survived, and the seizure phenotype displayed a moderate level of sensitivity (2 ~ 4 out of 6). In the histopathologic analysis, there was no change in morphological features, and levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba-1) increased in the kainic acid-treated groups. However, there was no difference in the neuronal nuclei (NeuN) expression level. All the data showed that the responses in the kainic acid-treated group were similar across the three strains. In conclusion, our results suggest that the three sources of DBA/2 mice (DBA/2Kor1, DBA/2A, and DBA/2B) have similar pathological responses to kainic acid-induced seizures.Recently, minipig has been considered as an animal model that is appropriate for human disease model to study toxicology, pharmacology, and xenotransplantation. Nevertheless, minipigs are bred in various environment according to their use. Here, we suggest that minipigs used for research should be bred in well-controlled facility, comparing immune status of pigs raised in different breeding environment. DNA microarray was performed with ear skin and placenta of Landrace domestic pigs (DPs) and Minnesota germ-free minipigs (GPs). Their immune transcriptome was analyzed by gene ontology (GO) annotation database, based on criteria of |log2 fold change| ≥1 with P ≤ 0.05. As a result, we found that immune related genes in the ear skin of DPs were highly activated, compared to GPs. On the other hand, no significant s were found in the placenta. Quantitative real-time PCR (qRT-PCR) was performed in five candidate immune genes. Their fold changes were consistent with the results from DNA microarray (P ≤ 0.05). In conclusion, we experimentally proved that porcine immune system was affected by different breeding environment, suggesting the importance of controlling microbes in animal room for the qualified research.An amendment to this paper has been published and can be accessed via the original article.
Although recombinant human soluble thrombomodulin (rTM) has been widely used to treat disseminated intravascular coagulation (DIC) in Japan, there is no consensus regarding rTM efficacy. Therefore, if the factors influencing rTM efficacy is revealed, it may be possible to demonstrate the effectiveness of rTM by limiting the patients who use rTM. This study investigated the factors of rTM treatment which influence DIC status.
This retrospective case-control study enrolled hospitalized adult patients treated with rTM from October 2010 to May 2020. Among these patients, 227 who were diagnosed with DIC according to the Japanese Association for Acute Medicine DIC scoring system were assessed. The primary endpoint was the 28-day mortality after rTM treatment. For Cox-proportional hazards model, explanatory factors determined using univariate analysis with p < 0.1 were used. In addition, some factors considered to affect DIC-related mortality such as age ≥ 75 years, rTM dose ≥380 U/kg, antithrombin III treatmients with PT-INR ≥ 1.67 and age ≥ 75 years.
Collagen, the most abundant protein in the animal kingdom, represents a promising biomaterial for regenerative medicine applications due to its structural diversity and self-assembling complexity. Despite collagen's widely known structural and functional features, the thermodynamics behind its fibrillogenic self-assembling process is still to be fully understood. In this work we report on a series of spectroscopic, mechanical, morphological and thermodynamic characterizations of high purity type I collagen (with a D-pattern of 65 nm) extracted from Wistar Hannover rat tail. Our herein reported results can be of help to elucidate differences in self-assembly states of proteins using ITC to improve the design of energy responsive and dynamic materials for applications in tissue engineering and regenerative medicine.
Herein we report the systematic study on the self-assembling fibrillogenesis mechanism of type I collagen, we provide morphological and thermodynamic evidence associated to different self-assembng different energy exchange mechanisms as a consequence of different aggregation routes.
Emphasis was made on the use of isothermal titration calorimetry (ITC) for the thermodynamic monitoring of fibrillogenesis stages of the protein. An overall self-assembly enthalpy value of 3.27 ± 0.85 J/mol was found. Different stages of the self-assembly mechanism were identified, initial stages take place at pH values lower than the protein isoelectric point (pI), however, higher energy release events were recorded at collagen's pI. Denatured collagen employed as a control exhibited higher energy absorption at its pI, suggesting different energy exchange mechanisms as a consequence of different aggregation routes.
Respiratory diseases impose an immense health burden worldwide and affect millions of people on a global scale. Reduction of exercise tolerance poses a huge health issue affecting patients with a respiratory condition, which is caused by skeletal muscle dysfunction and weakness and by lung function impairment. Virtual reality systems are emerging technologies that have drawn scientists' attention to its potential benefit for rehabilitation.
A systematic review and meta-analysis following the PRISMA guidelines was performed to explore the effectiveness of virtual reality gaming and exergaming-based interventions on individuals with respiratory conditions.
Differences between the virtual reality intervention and traditional exercise rehabilitation revealed weak to insignificant effect size for mean heart rate (standardized mean difference, SMD = 0.17; p = 0.002), peak heart rate (SMD = 0.36; p = 0.27), dyspnea (SMD = 0.32; p = 0.13), and oxygen saturation SpO
(SMD = 0.26; p = 0.096). In addition, other thods to accurately analyze the effects of virtual reality for individuals with respiratory conditions, especially for duration, virtual reality system type, adherence, adverse effects, feasibility, enjoyment, and quality of life.
Fructose plays an important role in the complex metabolism of uric acid in the human body. However, high blood uric acid concentration, known as hyperuricemia, is the main risk factor for development of gout. Therefore, we conducted an updated meta-analysis on the prevalence and geographical distribution of hyperuricemia among the general population in mainland China using systematic literature search.
Five electronic databases were used to search for relevant articles published until 2019. All calculations were conducted using the Comprehensive Meta-Analysis (CMA) software. We included 108 eligible articles (172 studies by sex, 95 studies by regions, and 107 studies by study type) and an overall sample size of > 808,505 participants.
The pooled prevalence of hyperuricemia among the general population in mainland China was 17.4% (95% CI 15.8-19.1%). Our subgroup analysis indicated that the pooled prevalence by regions ranged from 15.5 to 24.6%. Those living Northeast region and being males had the hiwas the first comprehensive study to investigate the overall prevalence of hyperuricemia in mainland China covering the six different regions.Hematopoietic stem cells (HSCs) have self-renewal capacity and differentiation potential into all lineages of blood cells throughout the lifetime of an organism. The function of HSCs gradually changes during aging. To date, various stress factors influencing HSC aging have been identified. The increased production of reactive oxygen species and DNA damage responses are causatively attributed to HSC aging. The increased apolarity is a prominent feature of aged HSCs, whereas it is less obvious in young HSCs. The bone marrow (BM) microenvironment niche is a crucial factor for HSC aging. Mesenchymal stem cells show skewed differentiation during aging, which leads to decreased bone formation and increased adipogenesis. The accumulation of adipocytes confers negative effects on hematopoiesis. Loss of sympathetic nerve fibers or adrenoreceptor β3 signaling induces premature HSC and niche aging. Epigenetic regulators such as polycomb group proteins and the sirtuin family of proteins act to prevent premature aging. Targeting these factors, several rejuvenation strategies for aged HSCs have been employed in mice. However, we still do not know whether these strategies can be extrapolated to human HSCs. Aging is frequently accompanied by the development of clonal hematopoiesis, which is called age-related clonal hematopoiesis (ARCH) or clonal hematopoiesis of indeterminate potential (CHIP). Most ARCH/CHIP mutations occur in genes encoding epigenetic regulators including DNMT3A, TET2, and ASXL1, which suggests the relevance of epigenetic drift during the aging process. ARCH/CHIP is a strong risk factor for subsequent hematologic cancer. Notably, it also has an impact on the development of non-malignant disorders such as coronary heart disease. Further studies are warranted to decipher the complete picture of molecular crosstalk that regulates HSC aging.
Neonatal hypoglycemia is the most common endocrine abnormality in children, which is associated with increased morbidity and mortality. The burden and risk factors of neonatal hypoglycemia in rural communities in sub-Saharan Africa are unknown.
To determine the prevalence and risk factors for neonatal hypoglycemia in Lira District, Northern Uganda.
This was a community-based cross-sectional study, nested in a cluster randomized controlled trial designed to promote health facility births and newborn care practices in Lira District, Northern Uganda. This study recruited neonates born to mothers in the parent study. Random blood glucose was measured using an On Call® Plus glucometer (ACON Laboratories, Inc., 10125 Mesa Road, San Diego, CA, USA). We defined hypoglycemia as a blood glucose of < 47 mg/dl. To determine the factors associated with neonatal hypoglycemia, a multivariable linear regression mixed-effects model was used.
We examined 1416 participants of mean age 3.1 days (standard deviation (SDf age and those who are delayed in the onset of breastfeeding.
The volume of withdrawn publications in scholarly disciplines has grown steadily, but there is little awareness about this issue in rehabilitation. The aim of this study was to analyze the extent of retracted articles pertaining to rehabilitation.
Retracted articles were searched in 4 different bibliographic databases from their inception to April 2020 PubMed, Web of Science, WikiLetters and Retraction Watch. Three independent reviewers assessed the relevance of the retrieved articles to the rehabilitation area.
Of 280 rehabilitation-related publications retracted between 1984 and 2020, 83 (29.6%) were published in 55 full open access journals and 197 (70.4%) were published in 147 traditional, non-open access or hybrid journals. In the last 10 years (2009-2018) there was a significant steady increase in both the total number of retractions (p < 0.005; r = 0.856; R
= 0.733) and retraction rate per year (p< 0.05; r = 0.751; R
= 0.564). However, the number of retractions represents a very small percentage (~ 0.
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