Miracle-dz/UniFAR-FTUs huggingface dataset:
SGI‐110 and entinostat therapy reduces lung tumor burden and reprograms the epigenome

The DNA methyltransferase (DNMT) inhibitor vidaza (5‐Azacytidine) in combination with the histone deacetylase inhibitor entinostat has shown promise in treating lung cancer and this has been replicated in our orthotopic lung cancer model. However, the effectiveness of DNMT inhibitors against solid tumors is likely impacted by their limited stability and rapid inactivation by cytidine deaminase (CDA) in the liver. These studies were initiated to test the efficacy of SGI‐110, a dinucleotide containing decitabine that is resistant to deamination by CDA, as a single agent and in combination with entinostat. Evaluation of in vivo plasma concentrations and pharmacokinetic properties of SGI‐110 showed rapid conversion to decitabine and a plasma half‐life of 4 hr. SGI‐110 alone or in combination with entinostat reduced tumor burden of a K‐ras/p53 mutant lung adenocarcinoma cell line (Calu6) engrafted orthotopically in nude rats by 35% and 56%, respectively. SGI‐110 caused widespread demethylation of more than 300 gene promoters and microarray analysis revealed expression changes for 212 and 592 genes with SGI‐110 alone or in combination with entinostat. Epigenetic therapy also induced demethylation and expression of cancer testis antigen genes that could sensitize tumor cells to subsequent immunotherapy. In the orthotopically growing tumors, highly significant gene expression changes were seen in key cancer regulatory pathways including induction of p21 and the apoptotic gene BIK. Moreover, SGI‐110 in combination with entinostat caused widespread epigenetic reprogramming of EZH2‐target genes. These preclinical in vivo findings demonstrate the clinical potential of SGI‐110 for reducing lung tumor burden through reprogramming the epigenome.
Intervertebral Disc Degeneration in a Percutaneous Mouse Tail Injury Model

Objectives Intervertebral disc (IVD) degenerates progressively with age and after injuries. In this study, we aimed to characterize early molecular events underlying disc degeneration using a mouse tail IVD injury model. Design We have established a transcutaneous minimally invasive approach to induce mouse tail IVD injury under fluoroscopic guidance. Morphological and molecular changes in the injured IVDs are compared with the baseline features of adjacent intact levels. Results After needle puncture, tail IVDs exhibited time-dependent histological changes. The aggrecan neoepitope VDIPEN was evident from 2 days to 4 wks after injury. A disintegrin and metalloproteinase domain-containing protein 8 (adam8) is a surface protease known to cleave fibronectin in the IVD. Gene expression of adam8 was elevated at all time points after injury, whereas the increase of C-X-C motif chemokine ligand (cxcl)-1 gene expression was statistically significant at 2 days and 2 wks after injury. Type 1 collagen gene expression decreased initially at day 2 but increased at 2 wks after injury, whereas no significant change in type 2 collagen gene expression was observed. The extracellular matrix gene expression pattern is consistent with fibrocartilage formation after injury. Conclusions Mouse tail IVDs degenerate after needle puncture, as demonstrated by histological changes and aggrecan degradation. The minimally invasive tail IVD injury model should prove useful to investigators studying mechanisms of IVD degeneration and repair.
Defining child abuse in Hong Kong

Definitions of child abuse are culturally driven. Hong Kong, with a predominantly Chinese population, has managed to eradicate much of the societal abuse that children suffer elsewhere in Asia. Professional and government attention has now shifted to child abuse and neglect within the family. The paper, based on interviews with key professionals. analysis of policy documents and practice records examines traditional Chinese parent-child relationships. the status of parental authority and corporal punishment and changes in contemporary Hong Kong family life. It goes on to outline the development of responses to child abuse in Hong Kong, some of the dilemmas that professionals face in defining abuse and areas for future research.
Antidiabetic Potentials of a Novel Polyherbal Preparation Formulated According to Principles of Siddha System of Medicine

According to the principles of Siddha system of medicine, the following polyherbal preparation consisting of 5 plant parts in equal ratio namely, Asparagus racemosus, Emblica officinalis, Salacia oblonga, Syzygium aromaticum, and Tinospora cordifolia was formulated to treat experimental type 2 diabetic rats. So, using plants having aphrodisiac property in the formulation is a rational approach and first of its kind, as there have been no reports so far. Phenolics and other bioactive compounds present in polyherbal preparation may be responsible for lipid-lowering effects and strong antioxidant activity. Polyherbal preparation treatment reverted the activities of glycolytic and gluconeogenic enzymes that are disturbed in diabetic rats. It is concluded that polyherbal preparation treatment improves deranged lipid profile, antioxidant status, glycogen content, and decreases lipid peroxidation, which provides stability to membrane integrity and thus favors insulin receptor to achieve better glucose tolerance through a holistic approach.
Investigating the Relationship Between the Praying and Back Pain in Commercial Drivers

Background: Low back pain (LBP) is the most common and multifactor problem among the commercial drivers and the individual, social, psychological and occupational factors have important role in intensifying this pain. In various studies, the role of spiritual factor was investigated less compared to other factors. Objectives: The aim of this study was to investigate the effect of religious belief and praying on LBP among the commercial drivers. Patients and Methods: In this cross sectional study, commercial drivers in Karaj, Iran were studied during fall and winter 2010-2011. The variables include demographic data, years of commercial driving, chronic back pain (suffering from back pain for more than three months), pain intensity, job status and the religious belief and behavior. The tools of data collection were medical history, the researcher-made questionnaire about the religious belief, praying and visual analogue scale (VAS) with a numerical range of 1-10 for intensifying the LBP. Data were compared by chi-square 2 and student t and regression tests. Results: Two hundred and forty two drivers with the mean age of 34.30 ± 5.21 investigated and 67 of them (27.68%) had chronic back pain. Forty two of them were truck man. The mean of pain severity for the back pain suffered drivers was 5.36 ± 1.11. The relationship between LBP occurrence and smoking, job group and positive attitude to role of praying in health was not significant. The difference of mean age and the job record in the drivers without back pain was significant. Also the outbreak of back pain in drivers who pray was less than the others and the LBP intensity in patients who pray consistently was less statistically. Conclusions: Praying plays an important role in decreasing LBP. It is recommended to consider the spiritual and religious issues along with regarding the improvement of healthy life style between the work forces and assessment of ergonomic problems.
Classification and Risk Factors for Cerebral Palsy in the Korle Bu Teaching Hospital, Accra: A Case–Control Study

Cerebral palsy (CP) is a lifelong neurodevelopmental condition caused by injury to the developing fetal or infant brain. In developed countries 75% to 80% of cases are as a result of prenatal brain injury. Data from developing countries are limited; however, a higher proportion of affected children may have perinatal or postnatal injury. The objectives were …
Antibody Distribution Against Nonenteropathic E. Coli: Relation to Age, Sex, and Breast Feeding

Escherichia coli have been the subject of a vast number of studies since first characterized more than 75 years ago. They constitute the predominant flora of the colon of many animal species, including man, and have been shown to be of great importance in nutrition, in the metabolism of drugs, in certain diarrheal diseases, and in infections of the urinary tract. Conflicting evidence has been presented concerning the role their products play in the pathogenesis of irreversible shock. 1-3 Under ordinary conditions, these organisms do not appear to disturb the host; in certain circumstances, however, such as during the neonatal period, with hypogammaglobulinemia, localized obstruction, excessive irradiation, adrenal cortical steroid therapy, and neoplasia, they may become invasive and threaten life. 4 Certain strains which possess hemolytic activity, skin-necrotizing power, 5 and resistance to the bactericidal activity of serum 6,7 at times appear to be more invasive than others. In general,
Incidence of and Risk Factors for Transferring Cancer Patients from Rehabilitation to Acute Care Units

Guo Y, Persyn L, Palmer JL, Bruera E: Incidence of and risk factors for transferring cancer patients from rehabilitation to acute care units. Am J Phys Med Rehabil 2008;87:647–653. Objectives:The aim of this study was to examine the clinical factors associated with transfer from an acute inpatient rehabilitation service to an inpatient oncology service. Design:Retrospective chart review in an inpatient rehabilitation unit within a tertiary cancer center. Participants included consecutive patients admitted to an acute inpatient rehabilitation unit (n = 98). The average age of these patients was 60 yrs old (range from 18 to 86). Main outcomes measures included the frequency of transfer and reason for transfer. Results:Thirty-five percent (34/98) of patients were transferred back to the oncology service during acute rehabilitation, among them, 12% was for planned cancer treatment and 88% for worsening medical conditions. Age, sex, tumor diagnosis, presence of metastatic lesion, and most abnormal laboratory values at rehabilitation admission were not significant factors for transferring. Significant factors for transfers were low albumin (P = 0.04), elevated creatinine levels (P = 0.01), tube feeding (P = 0.03), and a Foley catheter (P = 0.02). Those patients who were transferred back to the oncology service were more likely to die during hospitalization (15%, 5/33) and less likely to be discharged to home (52%, 17/33) compared with patients who were not transferred (2% death, 1/62; 90% home, 56/62, P < 0.0001). Conclusions:Transferring back to the acute oncology service is 35% among patients undergoing acute cancer rehabilitation.
Folate intake and the risk of oral cavity and pharyngeal cancer: A pooled analysis within the International Head and Neck Cancer Epidemiology Consortium

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual‐level data from ten case–control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43–0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43–0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45–0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43–4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4–20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34‐3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41‐20.8%). Our project of a large pool of case–control studies supports a protective effect of total folate intake on OPC risk.
Expression of the DNA Repair Enzyme, Photolyase, in Developmental Tissues and Larvae, and in Response to Ambient UV‐R in the Antarctic Sea Urchin Sterechinus neumayeri

Gene expression of the DNA repair enzyme, photolyase (E.C. 4.1.99.3) was examined in the gonads, eggs, embryos and larval stages of the Antarctic sea urchin, Sterechinus neumayeri. Partial sequencing of the gene revealed two highly conserved regions, including a 300 bp region representing the binding site for the cofactor flavin adenine dinucleotide. The second 1200 bp region, likely representing a second light‐harvesting cofactor binding site, was identified in a second sea urchin species, Strongylocentrotus frascicanus. Probes for photolyase were developed from the shorter sequence, and expression in sea urchin developmental tissue and stages, and in response to in situ exposure to ultraviolet radiation was quantified using PCR and RT‐qPCR, with concentrations of photolyase normalized to actin concentrations. Photolyase was expressed in all tissues and developmental stages examined. In controlled field‐based experiments in McMurdo Sound, Antarctica, we found evidence of both constitutive expression of photolyase and induction in response to in situ exposure of embryos to UV‐R. Induction of photolyase was observed in response to greater ambient UV‐R (such as shallower water depths or sea ice‐free regions).
Patients with Chronic Whiplash-Associated Disorders: Relationship Between Clinical and Psychological Factors and Functional Health Status

Schmitt MA, van Meeteren NL, de Wijer A, van Genderen FR, van der Graaf Y, Helders PJ: Patients with chronic whiplash-associated disorders: Relationship between clinical and psychological factors and functional health status. Objectives:To examine the relative contribution of cervical impairments and psychosocial factors to perceived disability among people with chronic whiplash-associated disorders. Design:A total of 86 patients with chronic whiplash-associated disorders participated in this observational, cross-sectional study. All patients were presented to outpatient physical therapy clinics. All patients completed the neck disability index. Depression, anxiety, and catastrophizing were measured with the Hospital Anxiety and Depression scale and the pain coping and cognition list, respectively. Cervical function was assessed by measuring the active range of motion. Stepwise and hierarchical regression analysis was used to estimate the contribution of cervical impairment and psychosocial functions to the variance in neck disability. Results:Depressive symptomatology and catastrophizing explained 61% of the variance in neck disability index scores. Catastrophizing explained 57% of the variance in neck disability index scores and 15% of the variance in the sum scores of active cervical rotations. Conclusions:Catastrophizing explained the variance in both perceived neck disability and, to a lesser extent, active range of cervical motion, which suggests that pain-related catastrophizing plays an important role in the physical complaints of patients with chronic whiplash-associated disorders when referred to a physical therapist.
Occurrence of 3-MCPD and glycidyl esters in edible oils in the United States

Fatty acid esters of 3-monochloropropanediol (3-MCPD) and glycidol are processing contaminants found in a wide range of edible oils. While both 3 MCPD and glycidol have toxicological properties that at present has concerns for food safety, the published occurrence data are limited. Occurrence information is presented for the concentrations of 3-MCPD and glycidyl esters in 116 retail and/or industrial edible oils and fats using LC-MS/MS analysis of intact esters. The concentrations for bound 3-MCPD ranged from below the limit of quantitation (<LOQ) to 0.09 mg kg−1 (ppm) in 22 unrefined oils and from 0.005 to 7.2 mg kg−1 (ppm) in 94 refined oils. The concentrations for bound glycidol ranged from <LOQ to 0.03 mg kg−1 (ppm) in unrefined oil samples and from <LOQ to 10.5 mg kg−1 (ppm) in processed oil samples. The highest concentrations for both 3-MCPD and glycidol were seen in refined palm oil and palm olein samples. Palm olein samples also contained a higher percentage of 3-MCPD in mono-ester form than any other type of oil.
Porphyrin and Nonporphyrin Photosensitizers in Oncology: Preclinical and Clinical Advances in Photodynamic Therapy

Photodynamic therapy (PDT) is now a well‐recognized modality for the treatment of cancer. While PDT has developed progressively over the last century, great advances have been observed in the field in recent years. The concept of dual selectivity of PDT agents is now widely accepted due to the relative specificity and selectivity of PDT along with the absence of harmful side effects often encountered with chemotherapy or radiotherapy. Traditionally, porphyrin‐based photosensitizers have dominated the PDT field but these first generation photosensitizers have several disadvantages, with poor light absorption and cutaneous photosensitivity being the predominant side effects. As a result, the requirement for new photosensitizers, including second generation porphyrins and porphyrin derivatives as well as third generation photosensitizers has arisen, with the aim of alleviating the problems encountered with first generation porphyrins and improving the efficacy of PDT. The investigation of nonporphyrin photosensitizers for the development of novel PDT agents has been considerably less extensive than porphyrin‐based compounds; however, structural modification of nonporphyrin photosensitizers has allowed for manipulation of the photochemotherapeutic properties. The aim of this review is to provide an insight into PDT photosensitizers clinically approved for application in oncology, as well as those which show significant potential in ongoing preclinical studies.
A contribution to reduce sampling variability in the evaluation of deoxynivalenol contamination of organic wheat grain

Fusarium head blight caused by different varieties of Fusarium species is one of the major serious worldwide diseases found in wheat production. It is therefore important to be able to quantify the deoxynivalenol concentration in wheat. Unfortunately, in mycotoxin quantification, due to the uneven distribution of mycotoxins within the initial lot, it is difficult, or even impossible, to obtain a truly representative analytical sample. In previous work we showed that the sampling step most responsible for variability was grain sampling. In this paper, it is more particularly the step scaling down from a laboratory sample of some kilograms to an analytical sample of a few grams that is investigated. The naturally contaminated wheat lot was obtained from an organic field located in the southeast of France (Rhône-Alpes) from the year 2008–2009 cropping season. The deoxynivalenol level was found to be 50.6 ± 2.3 ng g–1. Deoxynivalenol was extracted with a acetonitrile–water mix and quantified by gas chromatography-electron capture detection (GC-ECD). Three different grain sampling techniques were tested to obtain analytical samples: a technique based on manually homogenisation and division, a second technique based on the use of a rotating shaker and a third on the use of compressed air. Both the rotating shaker and the compressed air techniques enabled a homogeneous laboratory sample to be obtained, from which representative analytical samples could be taken. Moreover, the techniques did away with many repetitions and grinding. This study, therefore, contributes to sampling variability reduction in the evaluation of deoxynivalenol contamination of organic wheat grain, and then, at a reasonable cost.
Scope extension validation protocol: inclusion of analytes and matrices in an LC-MS/MS sulfonamide residues method

Validation is a required process for analytical methods. However, scope extension, i.e. inclusion of more analytes, other matrices and/or minor changes in extraction procedures, can be achieved without a full validation protocol, which requires time and is laborious to the laboratory. This paper presents a simple and rugged protocol for validation in the case of extension of scope. Based on a previously reported method for analysis of sulfonamide residues using LC-MS/MS, inclusion of more analytes, metabolites, matrices and optimisation for the extraction procedure are presented in detail. Initially, the method was applied only to liver samples. In this work, milk, eggs and feed were also added to the scope. Several case-specific validation protocols are proposed for extension of scope. Graphical Abstract
A Comparative Kinetic and Mechanistic Study Between Tetrahydrozoline and Naphazoline Toward Photogenerated Reactive Oxygen Species

Kinetic and mechanistic aspects of the vitamin B2 (riboflavin [Rf])‐sensitized photo‐oxidation of the imidazoline derivates (IDs) naphazoline (NPZ) and tetrahydrozoline (THZ) were investigated in aqueous solution. The process appears as important on biomedical grounds, considering that the vitamin is endogenously present in humans, and IDs are active components of ocular medicaments of topical application. Under aerobic visible light irradiation, a complex picture of competitive interactions between sensitizer, substrates and dissolved oxygen takes place: the singlet and triplet (3Rf*) excited states of Rf are quenched by the IDs: with IDs concentrations ca. 5.0 mm and 0.02 mm Rf, 3Rf* is quenched by IDs, in a competitive fashion with dissolved ground state oxygen. Additionally, the reactive oxygen species: O2(1Δg), O2•−, HO• and H2O2, generated from 3Rf* and Rf •−, were detected with the employment of time‐resolved methods or specific scavengers. Oxygen uptake experiments indicate that, for NPZ, only H2O2 was involved in the photo‐oxidation. In the case of THZ, O2•−, HO• and H2O2 were detected, whereas only HO• was unambiguously identified as THZ oxidative agents. Upon direct UV light irradiation NPZ and THZ generate O2(1Δg.), with quantum yields of 0.2 (literature value, employed as a reference) and 0.08, respectively, in acetonitrile.