Miracle-dz/UniFAR-FTUs huggingface dataset:
Osseointegrated Oral implants

Fourteen Swedish teams outside the University of Gothenburg, each with minimally three years' experience in the Nobelpharma osseointegrated implant participated in a retrospective multiclinic study. The total number of consecutively inserted implants at the 14 clinics was 8139. The outcome of every implant was reported and all implant failures, irrespective of when they occurred, were published. The success criteria included absence of implant mobility, absence of radiolucent zones on x-rays, and an annual bone loss after the first year of less than 0.2 mm. In the mandible 334 implants were followed for five to eight years, with only three failures, for a success rate of 99.1%. In the maxilla 106 implants were followed for five to seven years, with a success rate of 84.9%. In irradiated and grafted mandibles, 56 implants were inserted and none was lost during a follow-up of up to five years. In the irradiated maxilla there were 16 implants inserted with three reported failures and in the grafted upper jaw 71 implants were inserted with 12 failures. The proportions of mandibular and maxillary sleeping implants were 0.8 and 0.3%, of patient drop-out implants 0.3 and 0.6%, and of patient death implants 0.9 and 1.2%, respectively. It was concluded that the osseointegrated implant, if inserted according to the guidelines of Branemark, results in a very high degree of clinical success, thereby meeting any published oral implant success criteria.
Ras/cAMP-dependent Protein Kinase (PKA) Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast*

Background: Whi3 is known as a negative regulator of the G1 cyclin. Results: The phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function. Conclusion: Phosphorylation of Whi3 by PKA plays an important role as a direct modulator of cell fate decision in response to external signals. Significance: A new aspect of the interface between the cell cycle and cell fate has been discovered. The Start/G1 phase in the cell cycle is an important period during which cells determine their developmental fate, onset of mitotic progression, or the switch to developmental stages in response to both external and internal signals. In the budding yeast Saccharomyces cerevisiae, Whi3, a negative regulator of the G1 cyclins, has been identified as a positive regulator of cell size control and is involved in the regulation of Start. However, the regulatory pathway of Whi3 governing the response to multiple signals remains largely unknown. Here, we show that Whi3 is phosphorylated by the Ras/cAMP-dependent protein kinase (PKA) and that phosphorylation of Ser-568 in Whi3 by PKA plays an inhibitory role in Whi3 function. Phosphorylation of Whi3 by PKA led to its decreased interaction with CLN3 G1 cyclin mRNA and was required for the promotion of G1/S progression. Furthermore, we demonstrate that the phosphomimetic S568D mutation of Whi3 prevented the developmental fate switch to sporulation or invasive growth. Thus, PKA modulated the function of Whi3 by phosphorylation, thus implicating PKA-mediated modulation of Whi3 in multiple cellular events.
Depressive symptomatology and the prevalence of cardiovascular risk factors among older men and women from Cyprus; the MEDIS (Mediterranean Islands Elderly) epidemiological study.

AIMS The purpose of this paper is to explore the link between symptoms of depression and the prevalence of cardiovascular risk factors in older adults. METHODS During 2005, 136 older men and 164 women from various parts of Cyprus agreed to participate in the study. The sampling was random and multistage (according to age-sex distribution of the referent population). All participants were living in the community and not in institutions. Among several socio-demographic, bioclinical, lifestyle and dietary characteristics, depressive symptoms were assessed using the short version of the Geriatric Depression Scale (GDS). RESULTS Participants without signs of depression, typically, have fewer cardiovascular risk factors (i.e. hypertension, hypercholesterolemia, diabetes and obesity) than those with moderate or severe symptoms. Even when behavioural variables (e.g. diet, smoking, exercise) are statistically controlled, participants that are higher than others on depression are more likely to have hypertension and/or hypercholesterolemia than those with lower scores. Every one-unit increase in GDS score (range 0-15) is associated with a 12% higher likelihood of having an additional cardiovascular disease risk factor. CONCLUSIONS Symptoms of depression are positively associated with the number of cardiovascular risk factors in 'healthy' older adults, irrespective of lifestyle behaviours (e.g. smoking, dietary intake and physical activity). RELEVANCE TO CLINICAL PRACTICE Healthcare providers should consider the implications of both the presence and nature of this relationship in their continuing care of older adults.
Soroprevalência de anticorpos para toxoplasmose, rubéola, citomegalovírus, sífilis e HIV em gestantes sergipanas

The seroprevalence of antibodies for HIV, syphilis, toxoplasmosis, cytomegalovirosis and rubella and its association with age and origin was investigated among pregnant women in Sergipe, northeastern Brazil. A total of 9,550 pregnant women (2,112 from the state capital and 7,438 from other municipalities) were enrolled in the study and consecutively tested during their first antenatal care visit in 2007. The following serum prevalences were found: syphilis (0.9%; 95% CI 0.7%-1.6%), HIV (0.14%; 95% CI 0.08%-0.2%), toxoplasmosis (IgG 69.3%; 95% CI 68.3%-70.2%; IgM 0.4%, 95% CI 0.3%-0.6%), cytomegalovirosis (IgG 76.6%, 95% CI 75.7%-77.5%; IgM 0.2%, 95% CI 0.09%-0.3%) and rubella (IgG 71.6%, 95% CI 70.7%-72.6%; IgM 0.1%, 95% CI 0.04%-0.2%). Toxoplasmosis seropositivity increased with age. The prevalences of IgG antibodies for toxoplasmosis, cytomegalovirus and rubella were higher in Aracaju (state capital) than in other municipalities in the State of Sergipe. The results showed that a large proportion of the pregnant women, particularly in municipalities other than the state capital, were susceptible to toxoplasmosis, rubella and cytomegalovirus, with a risk for their infants.
Relevance of perceived childhood neglect, 5‐HTT gene variants and hypothalamus–pituitary–adrenal axis dysregulation to substance abuse susceptibility

The hypotheses of (1) gene × environment interaction in the susceptibility to experiment with drugs and (2) hypothalamus–pituitary–adrenal (HPA) axis involvement in mediating the effects of early adverse experiences and gene variants affecting serotonin function on substance abuse vulnerability were tested by investigating in 187 healthy adolescents the possible relevance of 5‐HTT “S” polymorphism, childhood parental neglect reported retrospectively and HPA axis function to the susceptibility to experiment with illicit drugs. Higher frequency of the 5‐HTT SS genotype seems to be associated with an increased susceptibility to use illegal psychotropic drugs among the adolescents. At the same time, reduced maternal care perception was found to represent a key intermediate factor of the association between SS polymorphism and drug use, suggesting that genetic factors and parental behavior concur to drug use susceptibility. Our results also confirm the relationship between basal plasma levels of cortisol and adrenocorticotropic hormone (ACTH) on the one hand, and retrospective measures of neglect during childhood: the higher the mother and father neglect CECA‐Q scores, the higher the plasma levels of the two HPA hormones. Such positive relationship has been proved to be particularly effective and important when associated to the S‐allele, both in homozygote and heterozygote individuals. However, when tested together with genotype and parental neglect, the effect of HPA hormones such as cortisol and ACTH was not found to improve significantly the explanatory power of the risk model. © 2009 Wiley‐Liss, Inc.
Analysis of whole genome biomarker expression in blood and brain

The consistency of peripheral gene expression data and the overlap with brain expression has not been evaluated in biomarker discovery, nor has it been reported in multiple tissues from the same subjects on a genome wide transcript level. The effects of processing whole blood, transformation, and passaged cell lines on gene expression profiling was studied in healthy subjects using Affymetrix arrays. Ficoll extracted peripheral blood mononuclear cells (PBMCs), Epstein–Barr virus (EBV) transformed lymphocytes, passaged lymphoblastic cell lines (LCLs), and whole blood from Tempus tubes were compared. There were 6,813 transcripts differentially expressed between different methods of blood preparation. Principal component analysis resolved two partitions involving pre‐ and post‐transformation EBV effects. Combining results from Affymetrix arrays, postmortem subjects' brain and PBMC profiles showed co‐expression levels of summarized transcripts for 4,103 of 17,859 (22.9%) RefSeq transcripts. In a control experiment, rat hemi‐brain and blood showed similar expression levels for 19% of RefSeq transcripts. After filtering transcripts that were not significantly different in abundance between human cerebellum and PBMCs from the Affymetrix exon array the correlation in mean transcript abundance was high as expected (r = 0.98). Differences in the alternative splicing index in brain and blood were found for about 90% of all transcripts examined. This study demonstrates over 4,100 brain transcripts co‐expressed in blood samples can be further examined by in vitro and in vivo experimental studies of blood and cell lines from patients with psychiatric disorders. © 2010 Wiley‐Liss, Inc.
Families and drug use in Greece

The study at hand explores Greek problematic drug users’ perceptions of the progression of their drug using careers and family responses towards drug affected children in Greece. The methodology of the study entailed the use of semi-structured in depth-interviews. In total, 40 interviews with problematic drug users (PDUs) were conducted as well as 8 interviews with parents of PDUs. Participating drug users were asked to reflect on all stages of their problematic drug using careers, from initial contact with drugs to entering treatment facilities where they were contacted. Furthermore, they were asked to reflect on the role their families played in influencing the progression of those careers and on the impact they felt their drug use had on their families. Parents’ accounts were also collected to provide a fuller picture of the issues in question. The results of the study put forth the vital role of self perception, whether this derives from sense of self through practice or participation in social groups, in relation to drug use onset and escalation. It is suggested that drug use may resemble a learning curve where drug using peers are ascribed the role of ‘aids’. The perception of one’s use as problematic was for the most part related to heroin infringing upon all life domains. Entering treatment was found to be sometimes unrelated to the decision to quit drug use. When the two were synonymous, reported reasons behind such decisions centred on issues of self perception, sense of obligation towards the family and a desire to return to pre-drug use life styles and selves. Reported factors either promoting or hindering change are also discussed. The hugely influential role of the Greek family in the progression of problematic drug using careers is a further proposal made by the current study. The experience of living with addiction in the family home and the reported impact on families is also presented. The specific cultural context of Greece was also shown to be shaping family reactions as well as drug using participants’ choices of course of action and perception of self. The overall suggestion based on the findings of the study is that the experiences of both Greek problematic drug users and Greek families of drug affected relatives form a ‘variform universal’. The conveyed picture is similar to that portrayed in the global literature, albeit coloured by the specific cultural context within which these experiences were lived through.
Metabolic Inhibition of Sialyl-Lewis X Biosynthesis by 5-Thiofucose Remodels the Cell Surface and Impairs Selectin-Mediated Cell Adhesion*

Background: Sialyl-Lewis X (sLeX) is a fucosylated oligosaccharide that plays critical roles in cell adhesion. Results: 5-thiofucose is metabolized by cells to produce a new nucleotide sugar that impairs sLeX biosynthesis and cell adhesiveness. Conclusion: 5-thiofucose blocks fucose transfer within treated cells. Significance: 5-thiofucose should be useful in further elucidating the biological roles of sLeX. Sialyl-Lewis X (sLeX) is a tetrasaccharide that serves as a ligand for the set of cell adhesion proteins known as selectins. This interaction enables adhesion of leukocytes and cancer cells to endothelial cells within capillaries, resulting in their extravasation into tissues. The last step in sLeX biosynthesis is the α1,3-fucosyltrasferase (FUT)-catalyzed transfer of an L-fucose residue to carbohydrate acceptors. Impairing FUT activity compromises leukocyte homing to sites of inflammation and renders cancer cells less malignant. Inhibition of FUTs is, consequently, of great interest, but efforts to generate glycosyltransferase inhibitors, including FUT inhibitors, has proven challenging. Here we describe a metabolic engineering strategy to inhibit the biosynthesis of sLeX in cancer cells using peracetylated 5-thio-L-fucose (5T-Fuc). We show that 5T-Fuc is taken up by cancer cells and then converted into a sugar nucleotide analog, GDP-5T-Fuc, that blocks FUT activity and limits sLeX presentation on HepG2 cells with an EC50 in the low micromolar range. GDP-5T-Fuc itself does not get transferred by either FUT3 or FUT7 at a measurable rate. We further demonstrate that treatment of cells with 5T-Fuc impaired their adhesive properties to immobilized adhesion molecules and human endothelial cells. 5T-Fuc, therefore, is a useful probe that can be used to modulate sLeX levels in cells to evaluate the consequences of inhibiting FUT-mediated sLeX formation. These data also reveal the utility of using sugar analogues that lead to formation of donor substrate analogues within cells as a general approach to blocking glycosyltransferases in cells.
Genetic analysis of nitric oxide synthase 1 variants in schizophrenia and bipolar disorder

Nitric oxide (NO) is a neurotransmitter that acts as a second messenger of the N‐methyl‐D‐aspartate receptor and interacts with the dopaminergic and the serotonergic systems. NO involvement in pathological processes relevant to neuropsychiatric disorders stems from its ability to modulate certain forms of synaptic plasticity, and from its capacity to be transformed to a highly active free radical. Additionally, multiple links have been reported between the NO‐producing enzyme, nitric oxide synthase (NOS) 1, and both schizophrenia and bipolar disorder (BPD). RNA and DNA isolated from dorsolateral‐prefrontal cortices of schizophrenia patients, bipolar patients and controls (n = 26, 30 and 29, respectively) were donated by the Stanley Foundation Brain Collection. Gene expression was measured by Real‐Time‐PCR. Genetic polymorphisms were genotyped by restriction‐fragment length‐polymorphism analysis, and by product‐size determination of PCR products amplified with a fluorescent primer.Expression analysis of pan‐NOS1, as well as of 2 of its isoforms, “NOS1_1d” and “NOS1_1f”, which differ in their first exons and translational strength, revealed a trend for pan‐NOS1 over‐expression (P = 0.075) in schizophrenia patients (1.33‐fold), and significant over‐expression (P < 0.05) of NOS1_1d and NOS1_1f in this group (1.54‐fold and 1.61‐fold, respectively). No expressional alteration was observed in BPD. Polymorphisms at the promoters of NOS1_1d and NOS1_1f, previously shown to be functional in vitro, revealed no significant allelic or genotypic differences among clinical groups and showed no effect on these transcripts' expression. In conclusion, understanding the molecular mechanisms underlying the over‐expression of specific NOS1 isoforms, which is unique to schizophrenia, may assist in identifying targets for new drugs. © 2010 Wiley‐Liss, Inc.
Euthanasia and assisted suicide in Dutch hospitals: the role of nurses.

AIM To report a study on the role of nurses in euthanasia and physician-assisted suicide in hospitals, conducted as part of a wider study on the role of nurses in medical end-of-life decisions. BACKGROUND Issues concerning legislation and regulation with respect to the role of nurses in euthanasia and physician-assisted suicide gave the Dutch Minister for Health reason to commission a study on the role of nurses in medical end-of-life decisions in hospitals, homecare and nursing homes. METHOD A questionnaire was sent in 2003 to 692 nurses employed in 73 hospital locations. The response suitable for analysis was from 532 (76.9%) nurses. Data were quantitatively analysed using spss version 11.5 for Windows. RESULTS In almost half of the cases (45.1%), the nurse was the first with whom patients discussed their request for euthanasia or physician-assisted suicide. Consultations between physicians and nurses quite often took place (78.8%). In several cases (15.4%), nurses themselves administered the euthanatics with or without a physician. It is not self-evident that hospitals have guidelines concerning euthanasia/physician-assisted suicide. CONCLUSIONS In the decision-making process, the consultation between the physician and the nurse needs improvement. In administering the euthanatics, physicians should take responsibility and should not leave these actions to nurses. Guidelines may play an important role to improve the collaboration between physicians and nurses and to prevent procedural, ethical and legal misunderstandings. RELEVANCE TO CLINICAL PRACTICE Nurses in clinical practice are often closely involved in the last stage of a person's life. Consequently, they are often confronted with caring for patients requesting euthanasia or physician-assisted suicide. The results provide relevant information and may help nurses in defining their role in euthanasia and physician-assisted suicide, especially in case these practices should become legalised.
Role of p70S6K1-mediated Phosphorylation of eIF4B and PDCD4 Proteins in the Regulation of Protein Synthesis*

Background: mTORC1 directly phosphorylates p70S6K1 and the 4E-BPs. Results: Although necessary, eIF4E·eIF4G complex formation was insufficient for sustaining global rates of protein synthesis. Conclusion: p70S6K1-mediated phosphorylation of eIF4B and PDCD4 also was required to optimally stimulate protein synthesis. Significance: Both eIF4E·eIF4G complex formation and activation of p70S6K1 individually stimulate global rates of protein synthesis. Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5′-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.
The Role of Secretory Immunoglobulin A in the Natural Sensing of Commensal Bacteria by Mouse Peyer's Patch Dendritic Cells*

Background: Intestinal commensal bacteria are not ignored by the mucosal immune system, yet the mechanisms ensuring homeostatic communication are poorly defined. Results: Coating of commensals by SIgA mediates their targeting to Peyer's patch dendritic cells. Conclusion: SIgA is important for the natural dynamic host-microbiota dialogue. Significance: Beyond pathogens, immune surveillance function of SIgA applies to the control of commensal bacteria. The mammalian gastrointestinal (GI) tract harbors a diverse population of commensal species collectively known as the microbiota, which interact continuously with the host. From very early in life, secretory IgA (SIgA) is found in association with intestinal bacteria. It is considered that this helps to ensure self-limiting growth of the microbiota and hence participates in symbiosis. However, the importance of this association in contributing to the mechanisms ensuring natural host-microorganism communication is in need of further investigation. In the present work, we examined the possible role of SIgA in the transport of commensal bacteria across the GI epithelium. Using an intestinal loop mouse model and fluorescently labeled bacteria, we found that entry of commensal bacteria in Peyer's patches (PP) via the M cell pathway was mediated by their association with SIgA. Preassociation of bacteria with nonspecific SIgA increased their dynamics of entry and restored the reduced transport observed in germ-free mice known to have a marked reduction in intestinal SIgA production. Selective SIgA-mediated targeting of bacteria is restricted to the tolerogenic CD11c+CD11b+CD8− dendritic cell subset located in the subepithelial dome region of PPs, confirming that the host is not ignorant of its resident commensals. In conclusion, our work supports the concept that SIgA-mediated monitoring of commensal bacteria targeting dendritic cells in the subepithelial dome region of PPs represents a mechanism whereby the host mucosal immune system controls the continuous dialogue between the host and commensal bacteria.