Miracle-dz/UniFAR-FTUs huggingface dataset:
Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels

Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca2+ channels (T-channels) and γ-aminobutyric acid A (GABAA) receptors in the development and maintenance of post-incisional pain. We use neuroactive steroids with distinct effects on GABAA receptors and/or T-channels: Alphaxalone (combined GABAergic agent and T-channel inhibitor), ECN (T-channel inhibitor), CDNC24 (GABAergic agent), and compared them with an established analgesic, morphine (an opioid agonist without known effect on either T-channels or GABAA receptors). Adult female rats sustained the skin and muscle incision on the plantar surface of the right paw. We injected the agents of choice intrathecally either before or after the development of post-incisional pain. The pain development was monitored by studying mechanical hypersensitivity. Alphaxalone and ECN, but not morphine, are effective in alleviating mechanical hyperalgesia when administered preemptively whereas morphine provides dose-dependent pain relief only when administered once the pain had developed. CDNC24 on the other hand did not offer any analgesic benefit. Neuroactive steroids that inhibit T-currents—Alphaxalone and ECN—unlike morphine, are effective preemptive analgesics that may offer a promising therapeutic approach to the treatment of post-incisional pain, especially mechanical hypersensitivity.
Human Astrocytes Model Derived from Induced Pluripotent Stem Cells

Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has mainly focused on neurons because the protocols for generating astrocytes from iPSCs have not been fully established. The growing evidence of astrocytes’ contribution to neurodegenerative diseases has underscored the lack of iPSC-derived astrocyte models. In the present study, we established a protocol to efficiently generate iPSC-derived astrocytes (iPasts), which were further characterized by RNA and protein expression profiles as well as functional assays. iPasts exhibited calcium dynamics and glutamate uptake activity comparable to human primary astrocytes. Moreover, when co-cultured with neurons, iPasts enhanced neuronal synaptic maturation. Our protocol can be used for modeling astrocyte-related disease phenotypes in vitro and further exploring the contribution of astrocytes to neurodegenerative diseases.
Prevalence of enteric pathogens, intestinal parasites and resistance profile of bacterial isolates among HIV infected and non-infected diarrheic patients in Dessie Town, Northeast Ethiopia

Background Enteric pathogens like Salmonella and Shigella species as well as intestinal parasites (IPs) are among the main causative agents of diarrhea in people with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), particularly in low income countries like Ethiopia. Antimicrobial resistance against commonly prescribed drugs has become a major global threat. This study, therefore, aimed at determining the magnitude of Salmonella, Shigella and IPs infections, their predicting factors, and antimicrobial susceptibility pattern among HIV infected and non-infected diarrheic patients in Dessie town, Northeast Ethiopia. Methods A cross sectional study was conducted at three health facilities in Northeast Ethiopia between January 2018 and March 2018. Data on socio-demographic and associated risk factors were collected using structured questionnaire from 354 HIV infected and non-infected diarrheic outpatients. Fresh stool specimen was processed according to standard operating procedures. Data were entered and analyzed using SPSS version 22. Descriptive statistics was used to determine frequency, Bivariate and multivariate logistic regression analyses were performed to identify predicting factors associated with the outcome variable. P-value <0.05 were used to declare statistical significance. Results Among 354 diarrheic patients, 112 were HIV infected and 242 were HIV non-infected. The overall prevalence of intestinal parasite and bacterial infection among HIV infected versus non-infected, respectively, was 26 (23.2%) and 8 (7.1%) versus 50 (20.7) and 16 (6.6%). Salmonella was the highest in both groups, 6 (5.4%) vs 11 (4.5%). Most prevalent parasite was C. parvum, 9 (8%) among HIV+ while E. histolytica/dispar 39 (16.1%) among HIV-. Having bloody plus mucoid diarrhea, not utilizing latrine and drinking river or spring water were factors significantly associated with bacterial infection. Whereas, being illiterate or having primary level education, diarrhea lasting for 6–10 days, CD4 level between 200–500 cells/μl, not washing hand with soap showed significant association with IPs. The bacterial isolates were 100% susceptible to Ceftriaxone and 95.4% to Ciprofloxacin, while 100% resistant to Ampicillin and Amoxicillin. MDR was observed among 19 (79.2%) isolates. Conclusion Preventing and controlling infection by enteric pathogens as well as IPs require strengthening intervention measures. The 100% resistance of isolates to commonly prescribed antibiotics calls for expanding antimicrobial susceptibility testing so as to select appropriate antimicrobial agent and prevent emergence of drug resistant bacteria.
Therapeutic Effects of Gallic Acid in Regulating Senescence and Diabetes; an In Vitro Study

Gallic acid (GA), a plant-derived ubiquitous secondary polyphenol metabolite, can be a useful dietary supplement. This in vitro study’s primary purpose was to assess the anti-aging properties of GA using rat embryonic fibroblast (REF) cells, antidiabetic effects via pancreatic islet cells, and finally, elucidating the molecular mechanisms of this natural compound. REF and islet cells were isolated from fetuses and pancreas of rats, respectively. Then, several senescence-associated molecular and biochemical parameters, along with antidiabetic markers, were investigated. GA caused a significant decrease in the β-galactosidase activity and reduced inflammatory cytokines and oxidative stress markers in REF cells. GA reduced the G0/G1 phase in senescent REF cells that led cells to G2/M. Besides, GA improved the function of the β cells. Flow cytometry and spectrophotometric analysis showed that it reduces apoptosis via inhibiting caspase-9 activity. Taken together, based on the present findings, this polyphenol metabolite at low doses regulates different pathways of senescence and diabetes through its antioxidative stress potential and modulation of mitochondrial complexes activities.
Hydrology of the Sumikawa geothermal prospect, Japan

Abstract This article summarizes the principal characteristics of the natural fluid circulation system at the Sumikawa Geothermal Field in northern Japan and relates them to local geological structure. Extensive two-phase flow prevails at intermediate depths (500 to 1000 m), and a very high transmissivity zone is present below a depth of about 1 km. This zone contains fluids with temperatures exceeding 300°C and is a suitable target for possible future development.
Rituximab Use in Warm and Cold Autoimmune Hemolytic Anemia

Autoimmune hemolytic anemia is a rare condition characterized by destruction of red blood cells with and without involvement of complement. It is associated with significant morbidity and mortality. In warm autoimmune hemolytic anemia, less than 50% of patients remain in long-term remission following initial steroid therapy and subsequent therapies are required. Cold agglutinin disease is a clonal hematologic disorder that requires therapy in the majority of patients and responds poorly to steroids and alkylators. Rituximab has a favorable toxicity profile and has demonstrated efficacy in autoimmune hemolytic anemia in first-line as well as relapsed settings. Rituximab is the preferred therapy for steroid refractory warm autoimmune hemolytic anemia (wAIHA) and as part of the first- and second-line treatment of cold agglutinin disease. This article reviews the mechanism of action of rituximab and the current literature on its role in the management of primary and secondary warm autoimmune hemolytic anemia and cold agglutinin disease.
Establishment of an Immunocompetent Metastasis Rat Model with Hepatocyte Cancer Stem Cells

Simple Summary Cancer stem cells (CSCs) are considered responsible for the maintenance, metastasis, and recurrence of various tumors. Here, we isolated a novel CSCs, TW-1, which can self-renew, differentiate and resistant to sorafenib. We also established novel orthotopic and metastasis models in immunocompetent rats with TW-1. These immunocompetent animal model can provide a normal physiological condition for anti-cancer drug screening. Using machine learning, we predicted HCC (AUCs > 0.9) with eight biomarkers including 6 highly expressed in TW-1/HTC and 2 well-known biomarkers from recent HCC studies. In conclusion, our results showed that TW-1 was a novel rat CSC line, and the animal model established with TW-1, is not only useful for the study of metastasis of HCC but also preclinical cancer drug screening. Abstract Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality. Cancer stem cells (CSCs) are responsible for the maintenance, metastasis, and relapse of various tumors. The effects of CSCs on the tumorigenesis of HCC are still not fully understood, however. We have recently established two new rat HCC cell lines HTC and TW-1, which we isolated from diethylnitrosamine-induced rat liver cancer. Results showed that TW-1 expressed the genetic markers of CSCs, including CD133, GSTP1, CD44, CD90, and EpCAM. Moreover, TW-1 showed higher tolerance to sorafenib than HTC did. In addition, tumorigenesis and metastasis were observed in nude mice and wild-type rats with TW-1 xenografts. Finally, we combined highly expressed genes in TW-1/HTC with well-known biomarkers from recent HCC studies to predict HCC-related biomarkers and able to identify HCC with AUCs > 0.9 after machine learning. These results indicated that TW-1 was a novel rat CSC line, and the mice or rat models we established with TW-1 has great potential on HCC studies in the future.
Spirituality and Quality of Life among Parents of Adolescents with Spina Bifida

In this investigational cross-sectional study, we explored the relationships among caregiver burden, depressive symptoms, spirituality, and quality of life (QOL) in 58 parental caregivers of adolescents with spina bifida (SB). A hierarchical linear regression analysis provided evidence that depressive symptoms and caregiver burden were negatively related to QOL scores, but spirituality was positively related. We found a significant interaction between caregiver burden and spirituality, suggesting that spirituality moderates the relationship between caregiver burden and quality of life. The negative effect of caregiver burden on QOL decreased as spirituality increased. These results warrant further research into how caregiver burden and spirituality intersect and impact QOL in parental caregivers of adolescents with SB.
The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcome measures selected: the myostatin inhibition story, thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models have failed to translate into clinical benefit to patients have been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.
The Significance of Tau Aggregates in the Human Brain

Neurofibrillary degeneration has attracted the attention of neuroscientists as both a hallmark of the disease and a subject for experimentation for more than a century. Recent studies implicate phosphorylated tau (p-tau) directly in neurodegenerative disease pathogenesis, although the human data continue to raise questions. P-tau accumulates with age in a roughly hierarchical manner, but avoids abundance in the neocortex unless co-occurring with amyloid-β. Neurodegenerative tauopathies tend to have p-tau morphologies that differ from aging and Alzheimer’s disease. Tau isoforms (3R vs. 4R) have a tendency to vary with tauopathy phenotype for unknown reasons. Selective vulnerability to p-tau and spatial-temporal disconnect from amyloid-β are evident in aging. P-tau assessment at autopsy involves tissue decomposition, which may skew microanatomical observations toward limited biological meaning. Two major consensus guidelines for interpreting p-tau at autopsy emphasize the challenges of clinicopathologic correlation, and reinforce the observation that regional neurodegeneration is a better correlate of clinical signs than is proteinopathy. Despite the proliferation of interesting and novel theories related to tau-mediated pathogenesis, the weight of the human observations suggests that neurofibrillary degeneration is an epiphenomenal hallmark of aging and disease rather than an epicenter of neurotoxicity. This is consistent with numerous tau-targeted therapeutic strategies that have been unsuccessful to date.
Mendelian randomization study of telomere length and bone mineral density

Purpose: Some epidemiological studies and animal studies have reported a relationship between leukocyte telomere length (LTL) and bone mineral density (BMD). However, the causality underlying the purported relationship has not been determined. Here we performed a two-sample MR analysis to test the causal link between telomere length and BMD. Results: Our research suggested no causal link of LTL and BMD using IVW method. The weighted median, MR-Egger regression and MR.RAPS method yielded a similar pattern of effects. MR-Egger intercept test demonstrated our results were not influenced by pleiotropy. Heterogeneities among the genetic variants on heel estimated BMD and TB-BMD vanished after excluding rs6028466. “Leave-one-out” sensitivity analysis confirmed the stability of our results. Conclusion: Our MR analysis did not support causal effect of telomere length on BMD. Methods: We utilized 5 independent SNPs robustly associated with LTL as instrument variables. The outcome results were obtained from GWAS summary data of BMD. The two-sample MR analysis was conducted using IVW, weighted median, MR-Egger regression and MR.RAPS method. MR-Egger intercept test, Cochran’s Q test and I2 statistics and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities and stability of these genetic variants on BMD.
Comparison of clinical characteristics among younger and elderly deceased patients with COVID-19: a retrospective study

We aimed to compare the age-related clinical characteristics between younger and elderly deceased COVID-19 patients. This single-center retrospective study included 163 adult deceased COVID-19 patients who were admitted to Wuhan Union Hospital West Campus from January 12, 2020, to March 30, 2020. Demographic and clinical features were collected by reviewing the medical records. The median age of the 163 deceased patients was 69 (interquartile range [IQR], 62-78) years. They were classified as younger (age 18-69 years; 86/163, 52.8%) and elderly (≥70 years; 77/163, 47.2%) subjects. Younger deceased patients were more likely to develop fever (72/86 vs 54/77, P=0.039) than elderly deceased patients were while anorexia was (29/77 vs 19/86, P=0.029) more common in elderly deceased patients than in younger deceased patients. In multivariate analyses, age was a protective factor for acute cardiac injury of deceased COVID-19 patients (odds ratio [OR] 0.968, [95% confidence interval (CI), 0.940-0.997]; P=0.033) while chronic cardiac disease was a risk factor for acute cardiac injury of deceased COVID-19 patients (OR 2.660 [95%CI, 1.034-6.843]; P=0.042). Our study described the clinical characteristics of younger and elderly deceased COVID-19 patients and demonstrated that younger deceased patients were more likely to develop an acute cardiac injury.
Workforce Planning Models for Oral Health Care: A Scoping Review

Background: For health care services to address the health care needs of populations and respond to changes in needs over time, workforces must be planned. This requires quantitative models to estimate future workforce requirements that take account of population size, oral health needs, evidence-based approaches to addressing needs, and methods of service provision that maximize productivity. The aim of this scoping review was to assess whether and how these 4 elements contribute to existing models of oral health workforce planning. Methods: A scoping review was conducted. MEDLINE, Embase, HMIC, and EconLit were searched, all via OVID. Additionally, gray literature databases were searched and key bodies and policy makers contacted. Workforce planning models were included if they projected workforce numbers and were specific to oral health. No limits were placed on country. A single reviewer completed initial screening of abstracts; 2 independent reviewers completed secondary screening and data extraction. A narrative synthesis was conducted. Results: A total of 4,009 records were screened, resulting in 42 included articles detailing 47 models. The workforce planning models varied significantly in their use of data on oral health needs, evidence-based services, and provider productivity, with most models relying on observed levels of service utilization and demand. Conclusions: This review has identified quantitative workforce planning models that aim to estimate future workforce requirements. Approaches to planning the oral health workforce are not always based on deriving workforce requirements from population oral health needs. In many cases, requirements are not linked to population needs, while in models where needs are included, they are constrained by the existence and availability of the required data. It is critical that information systems be developed to effectively capture data necessary to plan future oral health care workforces in ways that relate directly to the needs of the populations being served. Knowledge Transfer Statement: Policy makers can use the results of this study when making decisions about the planning of oral health care workforces and about the data to routinely collect within health services. Collection of suitable data will allow for the continual improvement of workforce planning, leading to a responsive health service and likely future cost savings.
A modern scleractinian coral with a two-component calcite–aragonite skeleton

Significance Until now, all of the ca. 1,800 known modern scleractinian coral species were thought to produce skeletons exclusively of aragonite. Asymbiotic Paraconotrochus antarcticus living in the Southern Ocean is the first example of an extant scleractinian that forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. This discovery adds support to the notion that the coral skeletal formation process is strongly biologically controlled. Mitophylogenomic analysis shows that P. antarcticus represents an ancient scleractinian clade, suggesting that skeletal mineralogy/polymorph of a taxon, once established, is a trait conserved throughout the evolution of that clade. One of the most conserved traits in the evolution of biomineralizing organisms is the taxon-specific selection of skeletal minerals. All modern scleractinian corals are thought to produce skeletons exclusively of the calcium-carbonate polymorph aragonite. Despite strong fluctuations in ocean chemistry (notably the Mg/Ca ratio), this feature is believed to be conserved throughout the coral fossil record, spanning more than 240 million years. Only one example, the Cretaceous scleractinian coral Coelosmilia (ca. 70 to 65 Ma), is thought to have produced a calcitic skeleton. Here, we report that the modern asymbiotic scleractinian coral Paraconotrochus antarcticus living in the Southern Ocean forms a two-component carbonate skeleton, with an inner structure made of high-Mg calcite and an outer structure composed of aragonite. P. antarcticus and Cretaceous Coelosmilia skeletons share a unique microstructure indicating a close phylogenetic relationship, consistent with the early divergence of P. antarcticus within the Vacatina (i.e., Robusta) clade, estimated to have occurred in the Mesozoic (ca. 116 Mya). Scleractinian corals thus join the group of marine organisms capable of forming bimineralic structures, which requires a highly controlled biomineralization mechanism; this capability dates back at least 100 My. Due to its relatively prolonged isolation, the Southern Ocean stands out as a repository for extant marine organisms with ancient traits.
Global Trends in Child Obesity: Are Figures Converging?

Childhood obesity has become one of the most serious global health challenges of our time. The combined prevalence of overweight and obesity has rapidly increased worldwide during the last two decades, especially in some developing countries where obesity is reaching levels on a par with some industrialized countries, or even higher. This fast growth has occurred especially in countries in the midst of rapid social-economic transitions. Most international comparisons focus on the adult population while analyses focusing on the child population are more limited. Using the methodology developed by Phillips and Sul, this paper studies the worldwide evolution of children’s body mass index (BMI), overweight and obesity prevalence for a large sample of countries during the period 1975–2016. Our results indicate that the figures for BMI or the prevalence of obesity in different countries do not converge, while the opposite is the case for overweight prevalence in children. Furthermore, there is a non-linear relationship between obesity and income or human capital, indicating that low and middle-income countries require a strong initiative for health policies targeting obesity prevention.