Miracle-dz/UniFAR-FTUs huggingface dataset:
Essential Role Of High Glucose-Induced Overexpression Of PKCβ And PKCδ In GLP-1 Resistance In Rodent Cardiomyocytes

Purpose Myocardia in diabetic patients exhibit increased vulnerability after ischemia/reperfusion injury (IRI). It has been demonstrated that glucagon-like peptide-1 (GLP-1) has a protective effect on cardiomyocytes. Protein kinase C (PKC) acts as a key regulator of many signaling pathways including oxidative stress and apoptosis. Our hypothesis is that increased vulnerability of myocardia in diabetic patients is partly due to GLP-1 resistance. The aim of this study was to explore the role of PKC in GLP-1 resistance in diabetic cardiomyocytes. Methods Cardiac function of diabetic or non-diabetic mice after myocardial IRI was detected with or without administration of GLP-1 analog exendin-4. Impacts of diabetes mellitus on GLP-1R expression in myocardia after IRI were accessed by Western blot. By transfecting PKC isoforms siRNA, in vitro study helped to identify the exact PKC isoforms which contributed to the downregulatio n of GLP-1R or impaired post-receptor signaling pathways in rodent cardiomyocytes (H9C2 cells) cultured by high glucose. Results The cardioprotective effects of endogenous GLP-1 were impaired in diabetic mice after myocardial IRI and administration of exendin-4 had no significant effects in restoring cardiac function. GLP-1 receptor (GLP-1R) expression decreased in H9C2 cells cultured by high glucose and knockdown of PKCβ partly restored GLP-1R expression. Overexpression of PKCδ induced by high glucose in H9C2 cells impaired GLP-1 post-receptor anti-apoptotic signaling pathways by inhibition of Akt phosphorylation. Knockdown of both PKCβ and PKCδ significantly restored cardioprotective effects of GLP-1 in H9C2 cells cultured by high glucose. Conclusion Our study found out a new mechanism of GLP-1 resistance that high glucose-induced overexpression of PKCβ and PKCδ impaired cardioprotective effects of GLP-1 by downregulation of GLP-1R and inhibition of GLP-1 post-receptor anti-apoptotic signaling pathways, thus provided a new perspective in treating myocardial IRI in diabetic patients.
Effects of Health and Nutrition on Cognitive and Behavioural Development in Children in the First Three Years of Life: Part 2: Infections and Micronutrient Deficiencies: Iodine, Iron, and Zinc

The following paper and its accompanying paper (Grantham-McGregor SM, et al. Effects of health and nutrition on cognitive and behavioural development in children in the first three years of life. Part 1: Low birthweight, breastfeeding, and protein-energy malnutrition. Food Nutr Bull 1999;20:53–75) review the literature on the conditions that are prevalent and considered to be likely to affect child development and are therefore of public health importance. the reviews are selective, and we have generally focused on recent work, particularly in areas that remain controversial. the reviews are restricted to nutritional and health insults that are important in the first three years of life. Where possible, we have discussed the better studies. This paper considers the effects of infections and the major micronutrient deficiencies: iodine, iron, and zinc.
The essence of student-teacher connection in the student-teacher relationship in clinical nursing education

The trend toward humanistic nursing education has called for a transformed studentteacher relationship that fosters learning and growth of the teacher and the student. Although such a relationship has been purported to form the basis for student-teacher connection, there is an absence of research exploring student-teacher connection. The purpose of this study was to explore and describe undergraduate nursing students' experiences of student-teacher connection and the influence of student-teacher connection on the students' clinical learning experiences. The qualitative research method of interpretive description guided the study. Unstructured interviews and a focus group were used to collect data from eight senior and junior undergraduate nursing students. Data were analyzed using the process of constant comparative analysis. Analysis revealed four interrelated major categories that form a description of the students' experience of student-teacher connection: nature of connection, formation of connection, processes of connection, and outcomes of connection. The findings indicate that student-teacher connection is a positive influence on students' clinical learning experiences and their socialization as professional nurses. As well, connection has a value in and of itself that arises from the qualities of caring, knowing, trusting, respecting, and mutuality that are inherent in the connected student-teacher relationship. The connected clinical teacher is a positive influence on students' learning experiences. From a basis of compassionate competence and commitment to understanding students as whole persons, the connected CNT works with students in their learning experiences as a helper, advocate and coach, and supports their learning in a variety of ways. Within the connected relationship students are able to focus on learning, are highly motivated and enjoy their learning. Further,
A Clinical Study of Infective Endocarditis in Childhood

Purpose:Advances in the treatment of congenital heart disease and a decline in the incidence of rheumatic fever has led to changes in the causative organisms and the clinical outcome of infective endocarditis(IE). We sought to analyze the clinical outcome, prognostic factors, causative organisms and corresponding antibiotic sensitivity in IE. Methods:Retrospective analysis of medical records of 104 children diagnosed and treated with IE at Severance Hospital, Yonsei University College of Medicine from January 1986 to June 2003 was undertaken. According to the Duke criteria, 55 patients were classified into the definite group(DG) and possible group(PG). Results:Thirty one cases(56.4%) fulfilled the criteria for the definite group in the Duke criteria, whereas 24 cases(43.6%) fulfilled the criteria for the possible group. The most common chief complaint on admission was fever(93%). The most common infecting organism was Staphylococcus aureus, which was found in 14 cases(48.3%). Three cases(21.4%) of this organism were methicillin- resistant S. aureus(MRSA). Other causative organisms were α-streptococcus(seven cases, 24.1%), Staphylococcus epidermidis(three cases, 10.3%), Citrobacter freundii(one case, 3.8%), Enterococcus faecium(one case, 3.4%) and Candida albicans(three cases, 10.3%). Penicillin-resistant organisms were found in 90.5%(19/21) of total cases and the most sensitive antibiotics were vancomycin(13/13, 100 %) and teicoplanin(12/12, 100%). One case of IE due to MRSA unresponsive to vancomycin was treated with Arbekacin. Conclusion:The incidence of IE caused by S. aureus, especially MRSA, is increasing. Multi-drug resistant organisms are also emerging as a frequent cause of IE. Thus, in patients strongly suspected of having IE in patients with underlying heart disease, glycopeptides such as vancomycin combined with aminoglycosides should be considered, and if fever and positive blood cultures continue despite treatment with glycopeptides, a consideration of the use of new antibiotics may improve the treatment results. (Korean J Pediatr 2004;47:844-850)
Surgical options in extensive burns management

Background – hypothesis and objective: In the past decades, extensive burn care has improved to the extent that burn victims can now frequently survive. Current treatment of a severe burned patient extends beyond the preservation of life and function; the ultimate goal is the return of survivors, as full participants, back to their families, work field and communities. Methods: This paper is based on our experience in treating patients with extensive burns. We had two panels as follows: 148 subjects with extensive burns in one original retrospective study (2002-2009) and other 47 new patients with extensive burns enrolled in other original prospective study (2010-2011). We selected the subjects with extensive burns who received allotransplant (n = 59). Our study aimed to identify and quantify the main psychosocial difficulties in patients with extensive burns who received allotransplant, also taking into account the surgical procedures applied in each case. Results: One of the major problems a surgeon faces is the nature of the decision he has to make regarding a treatment (conservative versus operative), based on the exact determination of burn wound depth. In case of early excision, deep lesions and suitable grafting represent the chosen surgical treatment in our center. The benefits of skin allografts are well known due to their contribution to burn management. Conclusions & discussion: This paper is designed as a guideline and instruction manual to help those with less experience through particular situations in surgical burn care. Early excision and immediate coverage of the burn wounds represent nowadays the standard care for extensive burned patients. For patients with massive thermal injury, temporary coverage with allografts is essential. The use of allograft has multiple benefits because it plays both as physiologic and mechanical barriers.
Comparison of the Antigen Distribution of Two US Porcine Reproductive and Respiratory Syndrome Virus Isolates with that of the Lelystad Virus

One hundred 4-week-old cesarean-derived colostrum-deprived pigs were inoculated with one of two different US porcine reproductive and respiratory syndrome virus (PRRSV) isolates (VR2385, VR2431) or the European Lelystad virus to detect and compare the location and amount of virus antigen. Interstitial pneumonia, myocarditis, lymphadenopathy, and encephalitis were consistently seen in all three groups; however, disease and lesions were more severe in the VR2385 group. Immunohistochemical evaluation of formalin-fixed tissues revealed virus antigen in alveolar macrophages in lungs of 22/25, 14/25, 14/25, and 0/25 of the VR2385, VR2431, Lelystad, and control pigs, respectively. Follicular macrophages and dendritic cells in the lymph nodes of 14/25, 10/25, 10/25, and 0/25 pigs from the VR2385, VR2431, Lelystad, and control groups, respectively, stained positive for virus antigen. Similar cells in the tonsils from 25/25, 21/25, 23/25, and 0/25 pigs from the VR2385, VR2431, Lelystad, and control groups, respectively, stained positive for virus antigen. Other tissues and cells in which virus antigen was detected included macrophages and endothelial cells in the heart, macrophages, and interdigitating cells in the thymus, macrophages and dendritic cells in the spleen and Peyer's patches, and macrophages in hepatic sinusoids, renal medullary interstitium, and adrenal gland. PRRSV persisted in macrophages in the lung, tonsil, lymph node, and spleen for at least 28 days. Significantly more PRRSV antigen was detected in the lung (P < 0.01), lymph nodes (P ≤ 0.05), and tonsils (P < 0.05) of the VR2385 pigs than was detected in the same tissues of the VR2431 and Lelystad pigs. The cell types in which PRRSV antigen was detected and the distribution of PRRSV antigen-positive cells within particular tissues and organs were generally similar for the different virus inoculation groups despite differences in virulence of the isolates.
A review of efferent cholinergic synaptic transmission in the vestibular periphery and its functional implications.

It has been over sixty years since peripheral efferent vestibular terminals were first identified in mammals and yet the function of the efferent vestibular system remains obscure. One reason for the lack of progress may be due to our deficient understanding of the peripheral efferent synapse. Although vestibular efferent terminals were identified as cholinergic less than a decade after their anatomical characterization, the cellular mechanisms that underlie the properties of these synapses has had to be inferred. In this review we examine how recent mammalian studies have begun to reveal both nicotinic and muscarinic effects at these terminals and therefore provide a context for fast and slow responses observed in classic electrophysiological studies of the mammalian efferent vestibular system, nearly forty years ago. Although incomplete, these new results together with those of recent behavioral studies are helping to unravel the mysterious and perplexing action of the efferent vestibular system. Armed with this information, we may finally appreciate the behavioral framework in which the efferent vestibular system operates.
Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile.
A multihost bacterial pathogen overcomes continuous population bottlenecks to adapt to new host species

A model of bacterial host switching provides a window into the population dynamics of host adaptation. While many bacterial pathogens are restricted to single host species, some have the capacity to undergo host switches, leading to the emergence of new clones that are a threat to human and animal health. However, the bacterial traits that underpin a multihost ecology are not well understood. Following transmission to a new host, bacterial populations are influenced by powerful forces such as genetic drift that reduce the fixation rate of beneficial mutations, limiting the capacity for host adaptation. Here, we implement a novel experimental model of bacterial host switching to investigate the ability of the multihost pathogen Staphylococcus aureus to adapt to new species under continuous population bottlenecks. We demonstrate that beneficial mutations accumulated during infection can overcome genetic drift and sweep through the population, leading to host adaptation. Our findings highlight the remarkable capacity of some bacteria to adapt to distinct host niches in the face of powerful antagonistic population forces.
Leishmania aethiopica cell‐to‐cell spreading involves caspase‐3, AkT, and NF‐κB but not PKC‐δ activation and involves uptake of LAMP‐1‐positive bodies containing parasites

Development of human leishmaniasis is dependent on the ability of intracellular Leishmania parasites to spread and enter macrophages. The mechanism through which free promastigotes and amastigotes bind and enter host macrophages has been previously investigated; however, little is known about intracellular trafficking and cell‐to‐cell spreading. In this study, the mechanism involved in the spreading of Leishmania aethiopica and Leishmania mexicana was investigated. A significant increase in phosphatidylserine (PS) exhibition, cytochrome C release, and active caspase‐3 expression was detected (P < 0.05) during L. aethiopica, but not L. mexicana spreading. A decrease (P < 0.05) of protein kinase B (Akt) protein and BCL2‐associated agonist of cell death (BAD) phosphorylation was also observed. The nuclear factor kappa‐light‐chain enhancer of activated B cells (NF‐kB) signaling pathway and pro‐apoptotic protein protein kinase C delta (PKC‐δ) were downregulated while inhibition of caspase‐3 activation prevented L. aethiopica spreading. Overall suggesting that L. aethiopica induces host cell’s apoptosis during spreading in a caspase‐3‐dependent manner. The trafficking of amastigotes within macrophages following cell‐to‐cell spreading differed from that of axenic parasites and involved co‐localization with lysosomal‐associated membrane protein 1 (LAMP‐1) within 10 min postinfection. Interestingly, following infection with axenic amastigotes and promastigotes, co‐localization of parasites with LAMP‐1‐positive structures took place at 1 and 4 h, respectively, suggesting that the membrane coat and LAMP‐1 protein were derived from the donor cell. Collectively, these findings indicate that host cell apoptosis, demonstrated by PS exhibition, caspase‐3 activation, cytochrome C release, downregulation of Akt, BAD phosphorylation, NF‐kB activation, and independent of PKC‐δ expression, is involved in L. aethiopica spreading. Moreover, L. aethiopica parasites associate with LAMP‐rich structures when taken up by neighboring macrophages.
A Comparison of Training Modality and Total Genotype Scores to Enhance Sport-Specific Biomotor Abilities in Under 19 Male Soccer Players.

Suraci, BR, Quigley, C, Thelwell, RC, and Milligan, GS. A comparison of training modality and total genotype scores to enhance sport-specific biomotor abilities in under 19 male soccer players. J Strength Cond Res XX(X): 000-000, 2019-Soccer-specific training (SST) and small-sided games (SSGs) have been shown to develop physical proficiency in soccer. Research on genetics and epigenetics in the prescription of training is limited. The aims of this study were to compare the impact of 3 different SST/SSG methods and investigate if a total genotype score (TGS) influences training response. Subjects (n = 30 male soccer players, mean ± SD; age 17.2 ± 0.9 years, stature = 172.6 ± 6.2 cm; body mass = 71.7 ± 10.1 kg) were stratified into a "power" (PG) or "endurance" (EG) gene profile group, where a 15 single nucleotide polymorphism panel was used to produce an algorithmically weighted TGS. Training 1 (T1-SSGs only), training 2 (T2-SSGs/SST), and training 3 (T3-SST only) were completed (in that respective order), lasting 8 weeks each, interspersed by 4-week washouts. Acceleration (10-m sprint) was improved by T2 only (1.84 ± 0.09 seconds vs. 1.73 ± 0.05 seconds; Effect Size [ES] = 1.59, p < 0.001). Speed (30-m sprint) was improved by T2 (4.46 ± 0.22 seconds vs. 4.30 ± 0.19 seconds; ES = 0.81, p < 0.001) and T3 (4.48 ± 0.22 seconds vs. 4.35 ± 0.21 seconds; ES = 0.58, p < 0.001). Agility (T-test) was improved by T1 (10.14 ± 0.40 seconds vs. 9.84 ± 0.42 seconds; ES = 0.73, p < 0.05) and T3 (9.93 ± 0.38 seconds vs. 9.66 ± 0.45 seconds; ES = 0.66, p < 0.001). Endurance (Yo-Yo level 1) was improved by T1 (1,682.22 ± 497.23 m vs. 2,028.89 ± 604.74 m; ES = 0.63, p < 0.05), T2 (1,904.35 ± 526.77 m vs. 2,299.13 ± 606.97 m; ES = 0.69, p < 0.001), and T3 (1,851.76 ± 490.46 m vs. 2,024.35 ± 588.13 m; ES = 0.35, p < 0.05). Power (countermovement jump) was improved by T3 only (36.01 ± 5.73 cm vs. 37.14 ± 5.62 cm; ES = 0.20, p < 0.05). There were no differences in T1, T2, and T3 combined when comparing PG and EG. The PG reported significantly (χ(20) = 4.42, p = 0.035, ES = 0.48) better training responses to T3 for power than the EG. These results demonstrate the efficacy of SSGs and SSTs in developing biomotor abilities. Although these results refute talent identification through the use of a TGS, there may be use in aligning the training method to TGS to develop power-based qualities in soccer.
Cytotoxicity Of Chalcone Of Eugenia﻿ aquea Burm F. Leaves Against T47D Breast Cancer Cell Lines And Its Prediction As An Estrogen Receptor Antagonist Based On Pharmacophore-Molecular Dynamics Simulation

Background The 2ʹ,4ʹ-dihydroxy-6-methoxy-3,5-3-dimethylchalcone (ChalcEA) isolated from Eugenia aquea Burm f. leaves has potential anticancer activity against human breast-adenocarcinoma cell lines (MCF-7) with an IC50 value of 250 µM. However, its apoptotic activity on the T47D breast cancer cell lines which is involving caspase-3 has not been investigated. Materials and methods Therefore, this study aims to evaluate the cytotoxicity of ChalcEA on the T47D cell lines using the 2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST) method and to predict its possible antagonistic activity on the human estrogen receptor alpha (hERα) using pharmacophore and molecular dynamics (MD) methods. The in vitro test of 10 synthesized ChalcEA derivatives was also performed as an insight into the further development of its structure as an anticancer agent. Results It is shown that ChalcEA has an IC50 of 142.58 ± 4.6 µM against the hERα-overexpressed T47D breast cancer cell lines, indicating its possible mechanism of anticancer activity as an antagonist of hERα. Pharmacophore study showed that ChalcEA shares similar features with the known hERα antagonist, 4-hydroxytamoxifen (4-OHT), which has hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), ring aromaticity (RA), and hydrophobicity (Hy) features. Molecular docking showed that ChalcEA formed hydrogen bonds with Glu353 and Arg394, and hydrophobic interactions in a similar manner with 4-OHT. Moreover, MD simulations showed that ChalcEA destabilized the conformation of His524, a remarkable behavior of a known hERa antagonist, including 4-OHT. Furthermore, the 10 best chalcone derivatives resulted from pharmacophore- and docking-based screening, were tested against the T47D cell lines. None of the derivatives have better activity than ChalcEA. It is suggested that the functional groups at the B-ring of ChalcEA are interesting to be further optimized in the next studies. Conclusion ChalcEA might act as an antagonist toward hERα, thus warranting further investigation as a potential anticancer agent.
Alveolar Type 2 Epithelial Cells as Potential Therapeutics for Acute Lung Injury/Acute Respiratory Distress Syndrome.

Acute lung injury/acute respiratory distress syndrome is a common clinical illness with high morbidity and mortality, which is still one of the medical problems urgently needed to be solved. Alveolar type 2 epithelial cells are an important component of lung epithelial cells and as a kind of stem cells, they can proliferate and differentiate into alveolar type 1 epithelial cells, thus contributing to lung epithelial repairment. In addition, they synthesize and secrete all components of the surfactant that regulates alveolar surface tension in lungs. Moreover, alveolar type 2 epithelial cells play an active role in enhancing alveolar fluid clearance and reducing lung inflammation. In recent years, as more advanced approaches appear in the field of stem and progenitor cells in lung, many preclinical studies have shown that the cell therapy of alveolar type 2 epithelial cells has great potential effects for acute lung injury/acute respiratory distress syndrome. We reviewed the recent progress on the mechanisms of alveolar type 2 epithelial cells involved in the damaged lung repairment, aiming to explore the possible therapeutic targets in acute lung injury/acute respiratory distress syndrome.