Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and characterization of a novel mouse model of single and repetitive mild traumatic brain injury

Mild traumatic brain injury (mTBI) or concussion is the most common form of TBI, and although a single concussion rarely results in long-term neurological dysfunction, repeated mild traumatic brain injury (r-mTBI) is a recognized risk factor for later development of neurodegenerative disease. However, the mechanisms contributing to neurodegeneration following TBI remain obscure. Animal models provide a means to examine the factors and mechanisms involved in TBI in experiments that cannot be conducted using human participants. The purpose of this thesis was to develop and fully characterize a reproducible, non-invasive mTBI model that will facilitate the study of repetitive brain injury. In the present study, male wild type mice received a midline concussive blow via an electromagnetic impactor, tuned to produce an injury without fracturing the skull. The injured mice were used to examine the chronic neurobehavioral, neuropathological and biochemical outcomes following single and r-mTBI up to 18 months following injury. Importantly, our findings recapitulate many aspects of human long term TBI sequelae, in particular persistent neuroinflammation, white matter injury, and axonal pathology in the corpus callosum. Our results provide the first evidence that, whilst a single concussion produces transient neurobehavioral changes and pathology which remains static in the period following injury, r-mTBI produces behavioral and pathological changes which continue to evolve many months post injury. There have been a number of clinical studies implicating tau in TBI pathology. As such, we investigated the relationship between tau pathologies after trauma in a transgenic mouse model expressing all 6 isoforms of human tau protein on a null murine background (hTau). Our results revealed that that single and r-mTBI induced a modest cortical increase in the soluble fraction of three different p-tau epitopes at 24 h post last injury. Moreover, this increase was not associated with worse behavioral performance when compared to wild type animals. Therefore, tau hyperphosphorylation appears to have a contributory, but not primary, role in the acute phase post-injury. Additional prospective studies in both humans and animal models are required to characterize the contribution of tau to TBI sequelae. The experimental data presented here suggest that inflammation and axonal injury (as seen in both wild-type and hTau models) appear to play a role in the events following single or repetitive mTBI and strongly correlates with the behavioral changes post-injury. The relationship between a history of mTBI and neuroinflammation are likely to be complex and warrant further work to elucidate their association with neurodegenerative disease. This work represents the development of a novel model, and the demonstration of its relevance to human TBI. This model can now be used for further exploration of TBI-related effects and for evaluation of potential therapeutic and diagnostic approaches, as is discussed throughout the thesis.
Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancer cells via the apoptotic pathway

Shikonin is a natural naphthoquinone pigment that can suppress the growth of a number of cancer cell types. Paclitaxel is an antineoplastic chemotherapy drug, which is used for the treatment of various types of solid tumor cancer. However, acquired paclitaxel resistance results in the failure of therapy, and consequent metastasis and relapse. The aim of the present study was to investigate whether shikonin can sensitize esophageal cancer cells to paclitaxel-treatment and to elucidate the underlying mechanisms. The biological effects of these two agents on esophageal cancer cell lines KYSE270 and KYSE150 were investigated by MTT assay, cell cycle analysis, Annexin-V apoptosis assay, western blotting and reverse transcription-quantitative polymerase chain reaction. The results demonstrated that shikonin could significantly increase the cell growth inhibition effect induced by paclitaxel in the examined cell lines (P<0.001). The addition of shikonin to paclitaxel promoted cancer cell mitotic arrest and induced significantly higher levels of cell apoptosis. Notably, the mRNA and protein levels of Bcl-2 were downregulated, while p53 was upregulated in KYSE270 and KYSE150 cells following combined treatment. In summary, shikonin can sensitize esophageal cancer cells to paclitaxel-treatment by promoting cell mitotic arrest and reinforcing the susceptibility of esophageal cancer cells to apoptosis induced by paclitaxel, which is potentially associated with altered levels of Bcl-2 and p53.
Effect of prior ipsilateral lower extremity surgery on 2-year outcomes following hip arthroscopy for femoroacetabular impingement syndrome

Abstract The purpose of this study was to determine the influence of prior lower extremity surgery on patient reported outcomes following hip arthroscopy for femoroacetabular impingement syndrome (FAIS). Consecutive patients who underwent hip arthroscopy for FAIS and a prior history of ipsilateral lower extremity surgery were identified and matched 2:1 by age, gender, and body mass index (BMI) to controls without a history of lower extremity surgery. The minimal clinically important difference (MCID) and patient acceptable symptomatic state (PASS) were calculated for HOS–ADL, HOS–SS, and mHHS. Preoperative and 2-year postoperative patient reported outcomes of both groups were compared, and logistic regression was performed to determine whether lower extremity surgery influenced achieving MCID and PASS. A total of 102 patients (24.94%) with prior history of ipsilateral lower extremity surgery were identified. Ipsilateral orthopaedic knee surgery accounted for more than half (53.92%) of all prior surgeries. Patients with a history of ipsilateral lower extremity surgery had significant lower 2-year PROs, satisfaction, and greater pain when compared to patients without lower extremity surgery (P < 0.001 all). A history of ipsilateral lower extremity surgery was a negative predictor of achieving MCID for HOS–ADL and HOS–SS, as well as PASS for HOS–ADL, HOS–SS, and mHHS (P < 0.001 all). In conclusion, patients with prior lower extremity surgery were found to have inferior outcome scores and a lower likelihood of achieving clinically significant outcome improvement compared to patients without a history of lower extremity surgery at two years postoperatively.
Diagnosis and Prognosis of Severe Dengue

Dengue has a broad spectrum of clinical symptoms, ranging from asymptomatic infection, undifferentiated fever and dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). DHF and DSS are the most severe forms of the disease, as they involve bleeding and hypovolemic shock and may lead to death if they are not diagnosed early and treated correctly. Every year, about 36 million cases of DF, of which about 2.1 million cases are DHF/DSS resulting in 21,000 deaths among children and young adults, are reported. Dengue not only has negative effects on public health worldwide but also poses significant economic burden. However, no licensed vaccines or (specific) anti-viral therapies for prevention or treatment of dengue are available. Thus, timely diagnosis and an accurate prognosis of severe dengue in the first few days of illness for clinical triage, treatment management, disease surveillance and research activities are vital and very helpful. We conducted three studies aiming to identify early markers of dengue, especially severe dengue and identify prognostic markers of severe dengue in Vietnamese children with clinically suspected dengue within the first few days of the illness. The results firstly showed that plasma collected within the first week of the illness could be used for dengue diagnosis as well as differentiation between primary and secondary dengue virus infections. Secondly, the research showed that plasma concentration of NS1 correlated with plasma viraemia and associated with DSS. NS1 concentrations in enrolment plasma of patients within the first four days of illness could be used for predicting DSS in patients with DENV-1 or DENV-2 infections. Thirdly, in the first three days of illness, we observed differences in clinical and haematological profiles between patients with DHF and those with DF or other febrile illnesses. Logistic models were then generated using the early clinical characteristics and/or haematological profiles to predict patients who will develop DHF. Our findings also showed that a greater virus burden leads to an augmented cascade of plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12p70, IL-13, IFNγ and TNFα in DHF patients compared to DF patients. This thesis shows the results and also points out predictive models that may be used to prognosticate of severe dengue among patients with clinically suspected dengue who are admitted to hospital within the first few days of the illness.
Potential role of pharmacogenomics testing in the setting of enhanced recovery pathways after surgery

Abstract In 2001, a group of European academic surgeons created the Enhanced Recovery After Surgery (ERAS) study group and established the first official ERAS protocol. One of the most significant challenges during ERAS implementation is variability of drugs used throughout the perioperative period. Pharmacogenomic testing (blood or saliva) results (obtained within approximately 48 hrs) provide guidelines on how to prescribe the optimal drug with the optimal dosage to each patient based on an individual’s unique genetic profile. Pharmacogenomic testing of various methods of multimodal analgesia is an essential element of ERAS protocols spanning the entire perioperative period to ultimately optimize postoperative pain control. The key goal for anesthetic management in ERAS protocols is to facilitate rapid emergence by using the shortest acting agents available, thus accelerating recovery and reducing length of stay, hospital expenses, and postoperative complications. Postoperative nausea and vomiting (PONV) is an additional challenge that should be overcome to ensure an enhanced recovery and shorter length of stay with the use of antiemetics. Postoperative ileus (POI) can result in longer hospital stay with increasing susceptibility to associated morbidities along with an increase in associated hospitalization costs. Genetics-guided pharmacotherapy and its impact on clinical outcomes should be thoroughly studied for better understanding and managing drug administration in the settings of ERAS.
Etiology and Related Factors of Postoperative Delirium in Orthopedic Surgery

Background Delirium is a serious complication for elderly patients after orthopedic surgery. The purpose of this study was to assess the etiology and related factors of delirium after orthopedic surgery in Korea. Methods We retrospectively reviewed the medical records of 3,611 patients over 50 years who had orthopedic surgery. The age of patients (50s, 60s, 70s, and > 80s), type of anesthesia (general, spinal, and local), operation time (more than 2 hours vs. less than 2 hours), surgical site (spine, hip, knee, or others), and etiology (trauma or disease) were compared to determine possible risk factors of delirium after orthopedic surgery. Results Of 3,611 patients, 172 (4.76%) were diagnosed with delirium after orthopedic surgery. Postoperative delirium occurred in 1.18% in their 50s, 3.86% in their 60s, 8.49% in their 70s, and 13.04% in > 80s (p < 0.001). According to anesthesia type, 6.50% of postoperative delirium occurred after general anesthesia, 0.77% after spinal anesthesia, and 0.47% after local anesthesia (p < 0.001). More than 2 hours of operation was associated with higher occurrence of delirium than less than 2 hours was (5.88% vs. 4.13%, p = 0.017). For the etiology, 8.17% were trauma cases and 3.02% were disease (p < 0.001). Postoperative delirium occurred in 22 of 493 patients (4.46%) after spine surgery, 18 of 355 patients (5.07%) after hip surgery, 17 of 394 patients (4.31%) after knee surgery, and 15 of 1,145 patients (1.31%) after surgery at other sites (p < 0.001). Conclusions Postoperative delirium was more common in older patients who had surgery under general anesthesia, whose surgery took more than 2 hours, and who were hospitalized through the emergency room.
The Nurses Knowledge of Oropharyngeal Administration of Mother’s Breast Milk in Extremely Low Birth Weight Infants to prevent NEC Study

Aim: To investigate the knowledge base of full time newborn critical care nurses related to oropharyngeal administration of mother’s breast milk to reduce the risk and prevalence of NEC in ELBW infants. Background: While the use of mother’s breast milk is widely supported and accepted practice, the oropharyngeal administration of mother’s breast milk is a new occurrence in neonatal care. A review of the literature suggest that, while it demonstrates benefits for the infants, some neonatal nurses do not exhibit an awareness of the current research on oropharyngeal administration of mother’s breast milk to reduce the risk and prevalence of NEC in ELBW infant. As they have the most parent-infant contact and influence over whether oropharyngeal administration of mother’s breast milk is carried out, assessment of their knowledge base is important. Method: A quantitative, descriptive design with neonatal nurses (n= 37) was used. Findings: Multiple areas were identified in which neonatal nurse education could be improved through a short in-service or handout. The three main topics of education are the indications of oropharyngeal administration, how colostrum affects the microbial colonization of the oral cavity of a very low birth weight infant, and that an epidemiologic risk factor for NEC is that there is a history of enteral feeding. Creating some educational material for the health care workers involved in the care of these neonates could be beneficial in promoting the implementation by breaking down the barrier of lack of knowledge by the providers and nurses. NCCC NURSES KNOWLEDGE STUDY 3
Factors associated with smoking initiation among Saudi male adolescents: A longitudinal study

INTRODUCTION Knowing country-specific predictors of smoking behaviour for adolescents is crucial for successful smoking prevention programs. This study aims to assess demographic and socio-cognitive variables related to smoking initiation among Saudi male adolescents. METHODS Longitudinal data were collected at T1 (baseline) and at T2 (followup at 6 months) using a self-administered questionnaire. We assessed smoking behaviour and related demographic variables and socio-cognitive variables. Chi-squared tests and independent-samples t-tests were used to identify differences in baseline characteristics between smokers and non-smokers at T1. Furthermore, non-smokers at T1 were included in logistic regression analyses to examine the predictors of smoking initiation between T1 and T2. RESULTS At T1, the non-smokers who were included in further analysis were 523 (84.9%) of whom 48 (9.2%) had initiated smoking at T2. They differed significantly from non-initiators, including having a more positive attitude towards smoking, reporting more social norms, modelling and pressure to smoke, having a lower self-efficacy to refrain from smoking and higher intention to smoke in the future (all p<0.001). The regression analysis revealed that: adolescents with disrupted-families, being of low academic achievement, with relatively high monthly-income families, having more smoking-peers, high-perceived pressure to smoke from parents (p=0.002) and teachers (p=0.001), have smoking supportive-norms of parents and having high intention to smoke in the future (p<0.001) were at higher risk of being smokers. CONCLUSIONS Findings suggest that health-promoting programs should address strengthening of self-efficacy and enhancing refusal skills against modelling of peers, pressure and norms of parents.
An ounce of prevention

Life expectancy worldwide increased dramatically in the 20th century. While most babies born in 1900 lived 50 years or less, life expectancies now exceed 80 years in several countries, and there is no indication of a tapering off of this trend in the 21st century. With the exception of immunizations, these increases are not as much attributable to medical breakthroughs as they are to changes in lifestyle and better living conditions including clean water and better nutrition (1). Can the same be said for decreases in cancer mortality?
Management of Hypertension in Patients with Chronic Kidney Disease and End-stage Renal Disease

There is plenty of evidence in scientific literature that clearly demonstrates that elevated blood pressure (BP) levels reduce life expectancy. Hypertension (HTN) is a major contributor to one or more target organ damage, including of the heart, brain, eyes, and kidneys. Historically, major focus of HTN management was to prevent morbidity and mortality resulting from cardiovascular and cerebrovascular diseases. In the recent past multiple factors, i.e., role of the kidney in pathophysiology of HTN, increased prevalence of HTN in kidney diseases, and rapid deterioration of renal function in patients with uncontrolled HTN has led to increased awareness of benefits of BP management. About 10% of world population have some form of renal dysfunction and HTN is the most common comorbidity affecting 65–95% of patients with chronic kidney disease (CKD). [1] Prevalence and severity of HTN and hence the incidence of endorgan damage increases with declining renal function. [2] Elevated BP can occur as a consequence of CKD but is also a risk factor for CKD progression. Interaction between HTN and CKD is complex and pathophysiologically it is difficult to determine which process precedes the other. Age, race, obesity, diabetes mellitus, and cardiovascular disease are common risk factors for both HTN and CKD. [3] Coexistence of both is known to greatly increase the risk of cardiovascular and cerebrovascular events. Therefore, control of HTN is the first priority in the management of CKD both to slow CKD progression and prevent other target organ(s) damage. HTN accelerates kidney injury as impaired renal autoregulation allows transmission of high systemic pressures to the glomeruli, leading to hyperfiltration and accelerated glomerulosclerosis. [4] On the other hand, renal injury can cause HTN, by multiple mechanisms including decreased sodium excretion, poor volume control, enhanced activity of the sympathetic nervous system (SNS) and renin–angiotensin aldosterone system (RAAS), and endothelial dysfunction, etc.[5] HTN in this population is usually resistant or refractory requiring multiple antihypertensive agents of different mechanism of Abstract
Air pollution and chronic obstructive pulmonary disease

The health effects of air pollution have been subject to intense study in recent years. These effects have been found in short-term studies, which relate day-to-day variations in air pollution and health, and long-term studies. The present paper is a review of the epidemiological research conducted during the last 10 years. In this review, we discuss the evidence of relation between short term variations in ambient concentrations of air pollution and short-term health effects of chronic obstructive pulmonary disease (COPD). Epidemiological studies have shown that COPD patients are susceptible to the acute effects of air pollution, and that COPD explained an important part of the total number of deaths attributed to air pollution. Epidemiological research has identified more exacerbations during periods of increased pollution. Increases in black smoke particulate mater, sulphur dioxide, and nitrogen dioxide are associated with increases in respiratory symptoms, admissions for exacerbations, and COPD associated mortality. There is evidence that persons with pre-existing respiratory disease are more susceptible to the health effects of air pollution. Even a weak effect of air pollution on health will constitute an important problem, because of ubiquity of exposure for large populations.
Management of Hypertension in Coronary Artery Disease

Epidemiological studies have shown significant association of hypertension (HTN) with coronary artery disease (CAD). HTN has been shown to be a significant modifiable independent risk factor for the development and progression of CAD, heart failure (HF), chronic kidney disease, and stroke. HTN not only plays a major role in the initiation of atherosclerosis leading to CAD but also persistently elevated levels lead to rapid progression of the disease along with destabilization of vascular lesions, precipitating acute coronary events, and HF. [1] Various studies have shown that HTN conferred a greater adjusted relative risk of acute myocardial infarction (MI) than diabetes mellitus with national level surveys conducted in different countries in North America, Asia, and Africa indicating that HTN, on the one hand, has a high prevalence and, on the other hand, a low awareness among the patient group leading to poor control. [2,3] These cardiovascular (CV) risks attributable to HTN can be decreased significantly with optimal blood pressure (BP) control. The present article examines and discusses appropriate systolic BP (SBP) and diastolic BP (DBP) targets in patients with established CAD, the optimal choice of antihypertensive agents and evaluation of their efficacy in secondary prevention of CAD among patients with stable ischemic heart disease (SIHD) and acute coronary syndrome (ACS).
Alterations of Tumor Suppressor Genes Expression in Colorectal Cancer: Their Impact on Progression and Prediction of Patients Outcome

Background: Deregulation of tumor suppressor genes as APC, DCC and SMAD2 are related to tumorgenesis thus we aimed to investigate their expression among colorectal cancer to validate their relation with clinicopathological factors and the clinical outcome for CRC patients. Materials and Methods: Formalin-fixed paraffin samples from 115 colorectal cancer were investigated for APC, DCC and SMAD2 gene expression using quantitative PCR (QPCR) and their levels were analyzed versus clinicopathological factors and the overall survival (OS) of colorectal cancer patients. Results: A significant relation was reported between DCC and SMAD2 gene expression with clinical Original Research Article Swellam et al.; AJRB, 2(1): 1-11, 2018; Article no.AJRB. 40616 2 stages as they reported decrease expression among those with stage III. The three investigated genes were decreased significantly with poor histological differentiation colorectal cancer patients. The correlations between the expressions of the investigated genes revealed a significant correlation between SMAD2 and APC as well as between SMAD2 and DCC. Moreover patients with mean levels below and equal their expression values showed a considerable difference with OS. Conclusion: Gene expression of tumor suppressor genes APC, DCC and SMAD2 were significantly related to differential grading and patient's outcome thus pointing out their potential role as predictive markers for prognosis of colorectal cancer.