Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomics and Public Health Research: Can the State Allow Access to Genomic Databases?

Because many diseases are multifactorial disorders, the scientific progress in genomics and genetics should be taken into consideration in public health research. In this context, genomic databases will constitute an important source of information. Consequently, it is important to identify and characterize the State’s role and authority on matters related to public health, in order to verify whether it has access to such databases while engaging in public health genomic research. We first consider the evolution of the concept of public health, as well as its core functions, using a comparative approach (e.g. WHO, PAHO, CDC and the Canadian province of Quebec). Following an analysis of relevant Quebec legislation, the precautionary principle is examined as a possible avenue to justify State access to and use of genomic databases for research purposes. Finally, we consider the Influenza pandemic plans developed by WHO, Canada, and Quebec, as examples of key tools framing public health decision-making process. We observed that State powers in public health, are not, in Quebec, well adapted to the expansion of genomics research. We propose that the scope of the concept of research in public health should be clear and include the following characteristics: a commitment to the health and well-being of the population and to their determinants; the inclusion of both applied research and basic research; and, an appropriate model of governance (authorization, follow-up, consent, etc.). We also suggest that the strategic approach version of the precautionary principle could guide collective choices in these matters.
Experimental Yersinia enterocolitica infection in euthymic and T-cell-deficient athymic nude C57BL/6 mice: comparison of time course, histomorphology, and immune response

To elucidate the role of T lymphocytes in primary infection with Yersinia enterocolitica, we investigated the elimination rate of this pathogen, the histomorphology of tissue lesions, and the immune responses of athymic T-cell-deficient C57BL/6 nude mice and their euthymic littermates after parenteral infection with Y. enterocolitica of serotype O:8. While a low inoculum of 3 x 10(2) Y. enterocolitica cells (about 0.01 times the median lethal dose for normal C57BL/6 mice) was cleared by normal C57BL/6 mice within 7 to 10 days, athymic nude C57BL/6 mice developed progressive infections after this inoculum, leading to death on days 20 to 25 postinfection (p.i.). While normal C57BL/6 mice experienced short-term transient infections, nude mice exhibited a biphasic, progressive infectious process. Thus, in the early phase (days 1 to 7 p.i.), a rapid influx of CD11b/18-positive cells (Mac-1 antigen) and natural killer cells was evident in the spleens and livers of the nude mice. The late phase (from day 8 p.i. onward) was characterized by a rapid progression of the infection and a further influx of CD11b/18-positive cells into the liver accompanied by an increase in bacterial counts and development of tissue lesions particularly in the liver and spleen. In normal mice, granuloma-like lesions composed of CD11b/18-, CD4-, and CD8-positive cells could be observed. However, granulomata were not found in nude mice. Yersinia-specific immunoglobulin G antibodies appeared on day 15 p.i. in the sera of normal mice, while nude mice failed to develop significant antibody titers. Adoptive transfer of Yersinia-specific T cells into athymic nude mice mediated resistance to Y. enterocolitica infection and restored both the ability of granuloma formation and the production of specific antibodies. In summary, the data presented herein strongly suggest that T lymphocytes play an essential role in the defense of C57BL/6 mice against Y. enterocolitica.
Antimicrobial peptide coating of dental implants: biocompatibility assessment of recombinant human beta defensin-2 for human cells.

PURPOSE Artificial materials such as dental implants are at risk of bacterial contamination in the oral cavity. Human beta defensins (HBDs), small cationic antimicrobial peptides that exert a broad-spectrum antibacterial function at epithelial surfaces and within some mesenchymal tissues, could probably help to reduce such contamination. HBDs also have protective immunomodulatory effects and have been reported to promote bone remodeling. The aim of this study, therefore, was to investigate the influence of recombinant HBD-2 on the proliferation and survival of cells in culture. MATERIALS AND METHODS Human mesenchymal stem cells (hMSCs), human osteoblasts, human keratinocytes (control), and the HeLa cancer cell line (control) were incubated with recombinant HBD-2 (1, 5, 10, or 20 μg/mL). Cell proliferation and cytotoxicity were evaluated via a water-soluble tetrazolium salt (WST-1) and lactate dehydrogenase assays, respectively. RESULTS HBD-2 was not toxic in any tested concentration to hMSCs, osteoblasts, keratinocytes, or HeLa cells. Furthermore, proliferation of hMSCs and osteoblasts increased after treatment with HBD-2 at all tested concentrations, and keratinocyte proliferation increased when treated at 20 μg/mL. In contrast, HeLa cancer cells were not affected by HBD-2 as tested. CONCLUSIONS HBD-2 is not only biocompatible but also promotes proliferation of hMSCs, osteoblasts, and keratinocytes in culture. Further investigation of HBD-2 functional surface coating of artificial materials is recommended.
The Physical Activity Levels and Sedentary Behaviors of Latino Children in London (Ontario, Canada)

Objective: To assess the physical activity and sedentary behaviors of a sample of Latino children in London, Ontario, Canada. Methods: Seventy-four Latino children (54.1% male; mean age = 11.4) completed self-report questionnaires related to physical activity and sedentary behaviors. A subset of children (n = 64) wore Actical (Mini Mitter, Respironics) accelerometers for a maximum of four days. Results: Latino children self-reported moderate levels of physical activity (i.e., mean score of 2.8 on 5-point scale). Accelerometer data revealed that children spent an average of 50.0 min in moderate-to-vigorous physical activity (MVPA; 59.2 min on weekdays and 50.6 min on weekend days) and were sedentary for an average of 8.4 h (508.0 min) per day (533.5 min on weekdays and 497.7 min on weekend days). Children reported spending an average of 3.8 h (228 min) daily in front of screens—1.7 h (102 min) watching television, 1.2 h (72 min) on the computer, and 0.9 h (54 min) playing video games. Conclusions: This feasibility project provided a preliminary account of objectively measured daily physical activity and sedentary time among a sample of Latino children in Canada, as well as insight into the challenge of measuring these behaviors. Sedentary behavior reduction techniques should be explored and implemented in this young population, along with strategies to promote adherence to accelerometer protocols.
Relationship of sleep, respiration, and anesthesia in the porpoise: a preliminary report.

The porpoise, an air-breathing mammal whose habits are entirely aquatic, presents special problems of respiration, sleep, and anesthesia. These problems have been studied in three species, Tursiops truncatus, Lagenorhynchus obliquidens, and Phocoenoides dalli. The respiratory rhythm is unusual in that there is an extended pause-an apneustic plateau-between periods of expiration and inspiration. This rhythm has been observed under waking conditions, during sleep, and also when the animal is anesthetized. Two kinds of sleep behavior have been identified in Tursiops and Lagenorhynchus. In one of these, which is a light phase, the animal rests on the tank bottom for short periods, up to perhaps four minutes, and then comes to the surface to breathe. In a deeper phase the animal maintains itself at the surface for extended periods, breathing in an automatic fashion. In Phocoenoides no sleep behavior has been observed at any time.I have examined the special theory of Dr. John C. Lilly regarding respiration and sleep in the porpoise, which is based upon the assumption that respiration in this animal is altogether voluntary, and from my observations have concluded that respiration in the porpoise can be automatic or can be brought under voluntary control, just as in other mammals. Also the anesthetization of this animal can be carried out safely by methods that correspond closely to those employed in other animals.
Photolyzed rhodopsin catalyzes the exchange of GTP for bound GDP in retinal rod outer segments.

We have studied the binding of guanyl nucleotides to retinal rod outer segment membranes to determine how light activates a cyclic GMP phosphodiesterase and a GTPase. We found that rod outer segment membranes contain tightly bound radioactive GDP after incubation in the dark with [3H]GDP or [alpha-32P]GTP. Reconstituted membranes containing only rhodopsin and phospholipid bind almost no GDP. More than 80% of the radioactive GDP bound to rod outer segment membranes could be released by subsequent illumination. At low light levels, the rate and extent of GDP release were markedly enhanced by the presence of GTP or p[NH]ppG, a nonhydrolyzable analog of GTP. The kinetics of binding of p[NH]ppG paralleled the kinetics of release of bound GDP, indicating that p[NH]ppG was exchanged for bound GDP. The maximal amount of bound p[NH]ppG was 1 per 30 rhodopsins when photolyzed membranes were incubated with 10 micro M nucleotide. Under these conditions, p[NH]ppG binding was half-maximal when only 1 in 90,000 rhodopsins was photolyzed. This corresponds to the catalyzed exchange of 500 p[NH]ppG for bound GDP per photolyzed rhodopsin. We propose a light-activated GTP-GDP amplification cycle involving a guanyl nucleotide binding protein with GTPase activity (E). The essence of this cycle is that photolyzed rhodopsin catalyzes the formation of E . GTP from E . GDP (the major species in the dark) by nucleotide exchange. The formation of several hundred E . GTP per photolyzed rhodopsin may be the first stage of amplification in visual excitation.
The C Terminus of the Nucleoprotein of Influenza A Virus Delivers Antigens Transduced by Tat to the trans-Golgi Network and Promotes an Efficient Presentation through HLA Class I

ABSTRACT Cytotoxic T lymphocytes (CTLs) are the most powerful weapon of the immune system to eliminate cells infected by intracellular parasites or tumors. However, very often, escape mechanisms overcome CTL immune surveillance by impairing the classical HLA class I antigen-processing pathway. Here, we describe a strategy for CTL activation based on the ability of Tat to mediate transcellular delivery of viral proteins encompassing HLA class I-restricted epitopes. In this system, the recombinant protein TAT-NpFlu containing the transduction domain of Tat of human immunodeficiency virus type 1 fused to the amino acid region 301 to 498 of the nucleoprotein of influenza A virus is proven to sensitize different human cells to lysis by HLA-B27-restricted, Flu 383-391-specific CTL lines. The fusion protein is processed very effectively, since a comparable biological effect is obtained with an amount of protein between 1 and 2 orders of magnitude lower than that of the synthetic peptide. Interestingly, while part of TAT-NpFlu undergoes fast and productive cleavage, a large amount of it remains intact for up to 24 h. Confocal microscopy shows that TAT-NpFlu accumulates in the trans-Golgi network (TGN), where it starts to be detectable 1 h after transduction. Using TAT-NpFlu mutants and hybrid constructs, we demonstrate that enrichment in the TGN occurs only when the carboxy-terminal region of NpFlu (amino acids 400 to 498) is present. These data disclose an unconventional route for presentation of epitopes restricted for HLA class I molecules.
Pediatric IBD-unclassified Is Less Common than Previously Reported; Results of an 8-Year Audit of the EUROKIDS Registry

Background:Inflammatory bowel disease–unclassified (IBD-U) is diagnosed in ∼10% of pediatric and adolescent onset IBD patients. The EUROKIDS registry (2004) initiated by the Porto IBD working group of ESPGHAN prospectively monitors diagnostic workup of newly diagnosed pediatric and adolescent onset IBD patients. We aimed to describe diagnostic workup, phenotype, and change of diagnosis over time in pediatric IBD-U patients. Methods:Data were collected on children from 52 centers across 20 European countries and Israel, diagnosed with IBD from May 2005 through November 2013. Full endoscopy plus small bowel radiology was considered complete diagnostic workup. Participating centers reporting IBD-U patients were queried in 2014 for follow-up data. Results:IBD-U was the provisional first diagnosis in 265 of 3461 children (7.7%) (91/158 [58%] with pancolitis; 140 [53%] male), diagnosed more frequently under the age of 10 (median age 12.3 years, 89 [34%] under 10 years). Half (48%) had undergone complete diagnostic workup. Lack of small bowel radiology was the prevailing reason for incomplete workup. As a result of reinvestigations (endoscopy in 54%, radiology in 38%) during a median follow-up of 5.7 years (interquartile range, 2.5–7.8), a change in diagnosis from IBD-U to Crohn's disease (12%) or ulcerative colitis (20%) was reported. Conclusions:Only half of patients reported as IBD-U in EUROKIDS had undergone complete diagnostic workup. Follow-up with reinvestigations resulted in a reduction of IBD-U rate to 5.6%. A diagnosis of IBD-U becomes less likely in case of complete diagnostic workup. Implementation of clear diagnostic criteria will further reduce the rate of IBD-U in the future.
The Effect of Intestinal Parasitic Infection on the Clinical Outcome of Malaria in Coinfected Children in Cameroon

Background The interaction between intestinal parasites and malaria is still not clear. Data in published literature are conflicting. We studied the effect of intestinal parasitic infection (IPI) on the clinical outcome of malaria in coinfected children. Methods In a cross sectional study performed between October 2014 and September 2015, children infected with malaria, as demonstrated by the presence of asexual parasites in Giemsa stained blood films, were enrolled. Stool samples were obtained from participants and subjected to the formol-ether concentration technique for the detection of intestinal parasites. The Complete blood count was performed using an automated haematology analyser (Mindray, BC-2800). The risk ratio, Pearson’s chi-square and the student T test were all performed as part of the statistical analyses. Statistical significance was set at p < 0.05. Results In all, 405 children successfully took part in the study. The children were between 1 week and 120 months of age (mean ± SD = 41.5 ± 33.5). Coinfection with intestinal parasites was observed in 11.6%. The rate of severe malaria (SM) attack in this study was 10.9%. SM was not observed to be associated with age (p = 0.377) or gender (p = 0.387), meanwhile coinfection with intestinal parasites was associated with age (p = 0.003). Among SM cases, IPI prevalence was higher in children with mild (WHO group 3) severe malaria (p = 0.027). Overall, IPI was not observed to be associated with SM (p = 0.656) or malaria parasite density (p = 0.185) or haemoglobin concentration (p = 0.205). The main clinical features of SM observed were hyperpyrexia (68.2%), severe malarial anaemia (61.4%), and multiple convulsion (52.3%). Conclusion IPI was not observed to be associated with the severity of malaria, the malaria parasite density, and the haemoglobin concentration in coinfected children in Cameroon. The clinical outcome of malaria in children coinfected with intestinal parasites may depend on the geographical setting after all.
Instantaneous Volatility Seasonality of High-Frequency Markets in Directional-Change Intrinsic Time

We propose a novel intraday instantaneous volatility measure which utilises sequences of drawdowns and drawups non-equidistantly spaced in physical time as indicators of high-frequency activity of financial markets. The sequences are re-expressed in terms of directional-change intrinsic time which ticks only when the price curve changes the direction of its trend by a given relative value. We employ the proposed measure to uncover weekly volatility seasonality patterns of three Forex and one Bitcoin exchange rates, as well as a stock market index. We demonstrate the long memory of instantaneous volatility computed in directional-change intrinsic time. The provided volatility estimation method can be adapted as a universal multiscale risk-management tool independent of the discreteness and the type of analysed high-frequency data.
Average power handling capability of finite-ground thin-film microstrip lines over ultra-wide frequency ranges

Based on the distributed parameters extracted and the thermal model proposed to calculate the rise in temperature, the average power handling capabilities (APHCs) of finite-ground thin-film microstrip lines (TFMLs) on benzocyclobutene (BCB) and polyimide films over ultra-wide frequency ranges are investigated. Numerical results are given to show the enhancement in APHCs achieved by choosing appropriate metallization conductivity and thickness, BCB thermal conductivity, and polyimide thickness etc. It is believed that the proposed approach is useful in the design of practical TFML circuits.
Subperiosteal lmplantation of octacalcium phosphate (OCP) stimulates both chondrogenesis and osteogenesis in the tibia, but only osteogenesis in the parietal bone of a rat

Background: It is not known whether long bones and calvaria have distinct biological characteristics. Octacalcium phosphate (OCP), which is a precursor phase of the hydroxyapatite, has been reported to stimulate bone formation if implanted in the subperiosteal region of mouse calvaria. The present study was designed to investigate how the long bone and the calvarium respond to OCP implantation and to compare their biological characteristics.
Renin-Angiotensin System Modulates Oxidative Stress–Induced Endothelial Cell Apoptosis in Rats

The role of the renin-angiotensin system in oxidative stress–induced apoptosis of endothelial cells (ECs) was investigated using a rat model and cultured ECs. EC apoptosis was induced by 5-minute intra-arterial treatment of a rat carotid artery with 0.01 mmol/L H2O2 and was evaluated at 24 hours by chromatin staining of en face specimens with Hoechst 33342. Although activity of angiotensin-converting enzyme in arterial homogenates was not increased, administration of an angiotensin-converting enzyme inhibitor temocapril for 3 days before H2O2 treatment inhibited EC apoptosis, followed by reduced neointimal formation 2 weeks later. Also, an angiotensin II type 1 (AT1) receptor blocker (olmesartan) inhibited EC apoptosis, whereas angiotensin II administration accelerated apoptosis independently of blood pressure. Next, cultured ECs derived from a bovine carotid artery were treated with H2O2 to induce apoptosis, as evaluated by DNA fragmentation. Combination of angiotensin II and H2O2 dose-dependently increased EC apoptosis and 8-isoprostane formation, a marker of oxidative stress. Conversely, temocapril and olmesartan reduced apoptosis and 8-isoprostane formation induced by H2O2, suggesting that endogenous angiotensin II interacts with H2O2 to elevate oxidative stress levels and EC apoptosis. Neither an AT2 receptor blocker, PD123319, affected H2O2-induced apoptosis, nor a NO synthase inhibitor, NG-nitro-l-arginine methyl ester, influenced the effect of temocapril on apoptosis in cell culture experiments. These results suggest that AT1 receptor signaling augments EC apoptosis in the process of oxidative stress–induced vascular injury.
Core Breast Biopsies Showing Lobular Carcinoma In Situ Should Be Excised and Surveillance Is Reasonable for Atypical Lobular Hyperplasia.

OBJECTIVE The purpose of this article is to determine the upgrade rate to ductal carcinoma in situ (DCIS) or invasive carcinoma at excision at the same site after percutaneous breast biopsy findings of atypical lobular hyperplasia (ALH) or lobular carcinoma in situ (LCIS) using current imaging and strict pathologic criteria. MATERIALS AND METHODS From January 2006 through September 2013, 32,960 breast core biopsies were performed; 1084 (3.3%) core biopsies found ALH or classic LCIS. For 447 lesions in 433 women, this was the only high-risk lesion at that site, with no ipsilateral malignancy, and results of excision were available. RESULTS Among the 447 lesions, 22 (4.9%) were malignant at excision, including 10 invasive carcinomas (two grade 2 and eight grade 1; all node negative) and 12 DCIS. The upgrade rate of LCIS was 9.3% (10/108; 95% CI, 5.1-16.2%) and that of ALH was 3.5% (12/339; 95% CI, 2.0-6.1%; p = 0.02). After excluding five cases with radiologic-pathologic discordance and reclassifying one core from ALH to LCIS at review, the upgrade rate for LCIS remained higher (8.4%; 9/107; 95% CI, 4.5-15.2%) than that for ALH (2.4%; 8/335; 95% CI, 1.2-4.6%; p = 0.01). CONCLUSION Excision is recommended for LCIS on core biopsy because of its 8.4-9.3% upgrade rate. Excluding discordant cases, patients with other high-risk lesions or concurrent malignancy, the risk of upgrade of ALH was 2.4%. Surveillance at 6, 12, and 24 months can be performed in lieu of excision because a short delay in diagnosis of the few malignancies is not expected to cause harm.
Contrasting Influences of Central and Peripheral Opioids on Cardiac Baroreflex Sensitivity in Rabbits

Summary: We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 (µg/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 µg/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 µg/kg) and nitroglycerine (1-20 µg/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors