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Sökning: WFRF:(Hirsch Jan M.)

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2.
  • Birney, Ewan, et al. (författare)
  • Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
  • 2007
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
  • Tidskriftsartikel (refereegranskat)abstract
    • We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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4.
  • Rieke, Johanna Magdalena, et al. (författare)
  • SLC20A1Is Involved in Urinary Tract and Urorectal Development
  • 2020
  • Ingår i: Frontiers in Cell and Developmental Biology. - : FRONTIERS MEDIA SA. - 2296-634X. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies in developingXenopusand zebrafish reported that the phosphate transporterslc20a1ais expressed in pronephric kidneys. The recent identification ofSLC20A1as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role ofSLC20A1in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish orthologslc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detectedSLC20A1in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequencedSLC20A1in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelicde novovariants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novelde novovariant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact ofSLC20A1variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggestSLC20A1is involved in urinary tract and urorectal development and implicateSLC20A1as a disease-gene for BEEC.
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5.
  • Alimena, Juliette, et al. (författare)
  • Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider
  • 2020
  • Ingår i: Journal of Physics G. - : IOP Publishing. - 0954-3899 .- 1361-6471. ; 47:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton-proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments-as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER-to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.
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6.
  • Breznau, Nate, et al. (författare)
  • Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
  • 2022
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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7.
  • Khonsari, R H, et al. (författare)
  • Shape and volume of craniofacial cavities in intentional skull deformations
  • 2013
  • Ingår i: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 151:1, s. 110-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.
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8.
  • Hasséus, B., et al. (författare)
  • Immunotoxic effects of smokeless tobacco on the accessory cell function of rat oral epithelium
  • 1997
  • Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 105:1, s. 45-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Smokeless tobacco (ST) is known to adversely effect the oral mucosa, but knowledge about the influence on immune defence is limited. Few studies have investigated the effect of ST on the local immune response. In the present study, we have assessed the effect of a crude Swedish moist snuff (SS) extract, alkaloids, and nitrosamines on T-cell mitogenic response to Con A using epithelial cells, including Langerhans cells, of the rat oral mucosa as accessory cells. SS extract at a concentration of 4% reduced the T-cell proliferation by 50% (IC50 = 4%). Pretreatment of either oral epithelial cells or T-cells with SS extract also gave a significant inhibition of T-cell proliferation. This effect was not obtained following preincubation with SS components as alkaloids and different tobacco-specific nitrosamines (TSNA). None of the tested compounds were found to possess any mitogenic properties. This in vitro study showed that SS extract can evoke an immunosuppressive effect on mitogen-driven T-cell proliferation using cells from oral epithelium as accessory cells. This effect was more pronounced when SS extract was employed compared to when the single SS components were used alone.
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9.
  • Buitrago-Téllez, C. H., et al. (författare)
  • A comprehensive classification of mandibular fractures : a preliminary agreement validation study
  • 2008
  • Ingår i: International Journal of Oral and Maxillofacial Surgery. - : Elsevier BV. - 0901-5027 .- 1399-0020. ; 37:12, s. 1080-8
  • Tidskriftsartikel (refereegranskat)abstract
    • This study evaluates a comprehensive classification system for mandibular fractures based on imaging analysis. The AO/ASIF scheme, defining three fracture types (A, B, C), three groups within each type (e.g. A1, A2, A3) and three subgroups within each group (e.g. A1.1, A1.2, A1.3) with increasing severity from A1.1 (lowest) to C3.3 (highest) was used. The mandible is divided into two vertical units (I and V), two lateral horizontal units (II and IV) and one central unit (III) comprising the symphyseal and parasymphyseal region. Type A fractures are non-displaced, type B are displaced and type C are multifragmentary/defect injuries. Groups and subgroups are further defined in the classification system. Two classification sessions using semi-automatic software with 7 and 9 surgeons were performed to evaluate 100 fracture cases in the first session and 50 in the second. Inter-observer reliability and individual rater's accuracy were evaluated by kappa coefficient and latent class analysis, respectively. The analysis of inter-observer agreement for the detailed coding showed kappa coefficients around 0.50 with higher agreement among raters in the vertical units. This system allows standardization of documentation of mandibular fractures, although improvement in the definition of categories and their application is required.
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10.
  • Esposito, M, et al. (författare)
  • Biological factors contributing to failures of osseointegrated oral implants. (I) : Success criteria and epidemiology
  • 1998
  • Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 106:1, s. 527-551
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this review was to offer a critical evaluation of the literature and to provide the clinician with scientifically-based diagnostic criteria for monitoring the implant condition. The review presents the current opinions on definitions of osseointegration and implant failure. Further, distinctions between failed and failing implants are discussed together with the presently used parameters to assess the implant status. Radiographic examinations together with implant mobility tests seem to be the most reliable parameters in the assessment of the prognosis for osseointegrated implants. On the basis of 73 published articles, the rates of early and late failures of Brånemark implants, used in various anatomical locations and clinical situations, were analyzed using a metanalytic approach. Biologically related implant failures calculated on a sample of 2,812 implants were relatively rare: 7.7% over a 5-year period (bone graft excluded). The predictability of implant treatment was remarkable, particularly for partially edentulous patients, who showed failure rates about half those of totally edentulous subjects. Our analysis also confirmed (for both early and late failures) the general trend of maxillas, having almost 3 times more implant losses than mandibles, with the exception of the partially edentulous situation which displayed similar failure rates both in upper and lower jaws. Surgical trauma together with anatomical conditions are believed to be the most important etiological factors for early implant losses (3.60% of 16,935 implants). The low prevalence of failures attributable to peri-implantitis found in the literature together with the fact that, in general, partially edentulous patients have less resorbed jaws, speak in favour of jaw volume, bone quality, and overload as the three major determinants for late implant failures in the Brånemark system. Conversely, the ITI system seemed to be characterized by a higher prevalence of losses due to peri-implantitis. These differences may be attributed to the different implant designs and surface characteristics. On the basis of the published literature, there appears to be a number of scientific issues which are yet not fully understood. Therefore, it is concluded that further clinical follow-up and retrieval studies are required in order to achieve a better understanding of the mechanisms for failure of osseointegrated implants.
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11.
  • Esposito, M, et al. (författare)
  • Biological factors contributing to failures of osseointegrated oralimplants. (II) : Etiopathogenesis
  • 1998
  • Ingår i: European Journal of Oral Sciences. - 0909-8836 .- 1600-0722. ; 106:3, s. 721-764
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the present review is to evaluate the English language literature regarding factors associated with the loss of oral implants. An evidence-based format in conjunction, when possible, with a meta-analytic approach is used. The review identifies the following factors to be associated with biological failures of oral implants: medical status of the patient, smoking, bone quality, bone grafting, irradiation therapy, parafunctions, operator experience, degree of surgical trauma, bacterial contamination, lack of preoperative antibiotics, immediate loading, nonsubmerged procedure, number of implants supporting a prosthesis, implant surface characteristics and design. Excessive surgical trauma together with an impaired healing ability, premature loading and infection are likely to be the most common causes of early implant losses. Whereas progressive chronic marginal infection (peri-implantitis) and overload in conjunction with the host characteristics are the major etiological agents causing late failures. Furthermore, it appears that implant surface properties (roughness and type of coating) may influence the failure pattern. Various surface properties may therefore be indicated for different anatomical and host conditions. Finally, the histopathology of implant losses is described and discussed in relation to the clinical findings.
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12.
  • Esposito, M, et al. (författare)
  • Failure patterns of four osseointegrated oral implant systems
  • 1997
  • Ingår i: Journal of materials science. Materials in medicine. - 0957-4530 .- 1573-4838. ; 8:12, s. 843-847
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of this metanalysis was to investigate possible differences in failure patterns among four different osseointegrated oral implant systems. Only systems with a supposed scientific validation, based on long-term follow-up studies, were selected for this analysis, i.e. the Brånemark system, the Calcitek Integral system, the Interpore IMZ system and the Straumann ITI system. While several prospective reports could be found on the Brånemark system, only a few retrospective investigations concerning the ITI and the IMZ systems were available. No data on the Integral system could be employed. Despite these limitations, a substantial difference in failure patterns among various implant systems was observed. The Brånemark implants showed a higher incidence of early failures, though sharply decreasing over time. On the contrary, IMZ implant characterized by rougher surfaces displayed a lower incidence of early failures, but showed constant or increased failure rates over time. For the ITI implants, for example, a higher prevalence of late failures, attributable to chronic bacterial infection (peri-implantitis), was observed when compared to the Brånemark system. With the exception of the latter implant system, prospective long-term follow-up studies, using similar and well-defined success criteria, are needed for the others to confirm the current preliminary findings.
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14.
  • Ibrahim, S O, et al. (författare)
  • Immunohistochemical detection of p53 in non-malignant and malignant oral lesions associated with snuff dipping in the Sudan and Sweden
  • 1996
  • Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 68:6, s. 749-753
  • Tidskriftsartikel (refereegranskat)abstract
    • Immunohistochemistry was used to examine the expression of p53 in pre-malignant oral lesions and oral squamous-cell carcinomas (SCCs) from Swedish and Sudanese snuff-dippers, as well as in pre-malignant oral lesions and oral SCCs from non-snuff-dippers from the Sudan, Sweden and Norway. Of the 14 SCCs from Sudanese snuff-dippers, 21% (3/14) expressed p53. Of the 14, 60 and 41 SCCs from non-snuff-dippers from the Sudan, Sweden and Norway, 64% (9/14), 65% (39/60) and 68% (28/41) expressed p53, respectively. A statistically significant difference in expression of p53 was found in SCCs from Sudanese snuff-dippers compared to those from non-snuff-dippers from all/or any of the 3 countries. None of the suspected pre-malignant oral lesions from Sudanese snuff dippers or non-snuff-dippers expressed p53. Only 2 out of the 15 oral fibro-epithelial hyperplastic lesions from Swedish snuff-dippers expressed p53. Some of the oral epithelial dysplastic lesions, as well as the carcinoma in situ lesions from Norwegian non-snuff-dippers, expressed p53, while the oral fibro-epithelial hyperplastic lesions did not. The low relative frequency of p53 expression found in oral SCCs from snuff-dippers compared to those from non-snuff-dippers might suggest differences in mechanisms of oncogenic action induced by snuff. Alternatively, the pathogenesis of malignant oral lesions from snuff-dippers may follow a p53-independent pathway. In view of the unusually high levels of the tobacco-specific nitrosamines (TSNA) found in the type of snuff used in the Sudan, investigations of p53 mutations or oncogenes are needed.
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15.
  • Idris, AM, et al. (författare)
  • The Swedish snus and the Sudanese toombak : are they different?
  • 1998
  • Ingår i: Oral Oncology. - 1368-8375 .- 1879-0593. ; 34:6, s. 558-566
  • Tidskriftsartikel (refereegranskat)abstract
    • In Sweden, snuff (locally known as snus), was introduced since the year 1637. Presently, Sweden has the highest per capita consumption and sale figures of snuff in the world, and the habit is becoming increasingly popular. Snus is manufactured into a dry form used in the nasal cavity and a moist form used in the oral cavity. Snus manufactured for oral use is a moist ground tobacco of Dark Kentucky or Virginia species mixed with an aqueous solution of water and other blending ingredients. This form of snuff is found in two types: (1) loose and (2) portion-bag-packed. These are the most widely used. The loose moist form (1–2 g a quid) is the most popular type consumed by 73% of the males, followed by the portion-bag-packed form (0.5–1 g a quid), consumed by 13% of the males, while 14% of the males are mixed users. The majority of snus users place the quid in the vestibular area of the upper lip, and the prevalence among persons 15 years of age or older is 15.9% among males and 0.2% among females. The pH of snus has declined from a previous range of 8–9 to a range of 7.8–8.5, moisture content ranges 35–60% and nicotine content is in the order of 5–11 mg/g dry wt tobacco-specific N-nitrosamines (TSNAs) in micrograms (N′-nitrosonornicotine: NNN 5–9; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone: NNK 1–2; N′-nitrosoanatabine: NAT 2–5). In the Sudan, snuff, locally known as toombak, was introduced approximately 400 years ago. It is always processed into a loose moist form, and its use is widespread in the country. Tobacco used for manufacture of toombak is of the species Nicotiana rustica, and the fermented ground powder is mixed with an aqueous solution of sodium bicarbonate. The resultant product is moist, with a strong aroma, highly addictive and its use is widespread particularly among males. Its pH range is 8–11, moisture content ranges 6–60% and nicotine content is from 8 to 102 mg/g dry wt, and TSNAs contents in micrograms (NNN 420–1 550; NNK 620–7 870; NAT 20–290). Snus and toombak dippers develop a clinically and histologically characteristic lesion at the site of dipping. Probably due to control of the TSNAs in snus, this type of snuff is associated with a lower risk of cancer of the oral cavity (relative risk: RR 5–6-fold), whereas the risk for cancer of the oral cavity among toombak users was high (RR 7.3–73.0-fold). In conclusion, the two snuff products significantly differ in many aspects. Most notable differences are tobacco species, fermentation and ageing, nicotine and TSNAs content, pH, expression of the p53 tumour supressor gene, and keratin types 13, 14, and 19. It was, therefore, the object of the present study to highlight the oral health hazards of toombak, and to compare it with snus regarding the aforementioned differences.
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16.
  • Jalouli, Jamshid, et al. (författare)
  • Presence of human papilloma virus, herpes simplex virus and Epstein-Barr virus DNA in oral biopsies from Sudanese patients with regard to toombak use
  • 2010
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 39:8, s. 599-604
  • Tidskriftsartikel (refereegranskat)abstract
    • J Oral Pathol Med (2010) Using PCR/DNA sequencing, we investigated the prevalence of human papillomavirus (HPV), herpes simplex virus (HSV) and Epstein-Barr virus (EBV) DNA in brush biopsies obtained from 150 users of Sudanese snuff (toombak) and 25 non-users of toombak in formalin-fixed paraffin-embedded tissue samples obtained from 31 patients with oral dysplasias (25 toombak users and 6 non-users), and from 217 patients with oral cancers (145 toombak users and 72 non-users). In the brush tissue samples from toombak users, HPV was detected in 60 (40%), HSV in 44 (29%) and EBV in 97 (65%) of the samples. The corresponding figures for the 25 samples from non-users were 17 (68%) positive for HPV, 6 (24%) positive for HSV and 21 (84%) for EBV. The formalin-fixed samples with oral dysplasias were all negative for HPV. In the 145 oral cancer samples from toombak users, HPV was detected in 39 (27%), HSV in 15 (10%) and EBV in 53 (37%) of the samples. The corresponding figures for the samples from non-users were 15 (21%) positive for HPV, 5 (7%) for HSV and 16 (22%) for EBV. These findings illustrate that prevalence of HSV, HPV and EBV infections are common and may influence oral health and cancer development. It is not obvious that cancer risk is increased in infected toombak users. These observations warrant further studies involving toombak-associated oral lesions, to uncover the possible mechanisms of these viral infections in the development of oral cancer, and the influence of toombak on these viruses.
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17.
  • Jalouli, Jamshid, et al. (författare)
  • Prevalence of viral (HPV, EBV, HSV) infections in oral submucous fibrosis and oral cancer from India
  • 2010
  • Ingår i: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 130:11, s. 1306-1311
  • Tidskriftsartikel (refereegranskat)abstract
    • Conclusion: There is a high prevalence of human papilloma viruses (HPV) in oral submucous fibrosis (OSMF) and the etiologic implication of this finding warrants further studies. Objective: The prevalence of oral squamous cell carcinoma (OSCC) and OSMF is high in India, and the diseases are partly attributed to high consumption of betel quid containing areca nut and tobacco. This study investigated the prevalence of HPV, herpes simplex virus (HSV), and Epstein-Barr virus (EBV) DNA in two groups of patients using betel quid with tobacco, those with OSMF (n = 12) and those with OSCC (n = 62). Methods: DNA was extracted from all the samples and viral genome was examined by PCR/DNA sequencing. HPV-positive samples were analyzed separately for the high-risk types HPV 16 and 18. Results: HPV DNA, HSV DNA, and EBV DNA were detected in 11 (91%), 1 (8%), and 3 (25%) of the 12 samples from patients with OSMF compared with 15 (24%), 3 (5%), and 18 (29%), respectively, from 62 patients with OSCC. HPV 16 and 18 DNA was detected in 8/12 (67%) in the OSMF group and 10/62 (16%) in the OSCC group. The difference between presence of HPV DNA in OSMF and OSCC groups was statistically significant, while the difference between HSV and EBV DNA content in OSMF and OSCC groups was insignificant.
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18.
  • Jalouli, Miranda M, et al. (författare)
  • Association of Human Papilloma Virus infection in healthy oral mucosa, oral dysplasia and oral squamous cell carcinoma
  • 2015
  • Ingår i: Journal of Oral Health and Dental Management. - 1583-5588. ; 14:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Human papillomavirus (HPV) is an important risk factor for development of oral cancer; however, the integrational status of the virus into the host DNA association between HPV infection and oral squamous cell carcinoma (OSCC) is still uncertain has not been investigated to the same extent. The objective of the present study was to investigate the prevalence of consensus HPV, and HPV-16 and its integration status, in healthy oral mucosa, oral epithelial dysplasia (OED), and OSCC samples.Materials and Methods: The study material consisted of 26 fresh, normal oral mucosa samples, and 53 and 27 paraffin-embedded OED and OSCC samples, respectively. The specimens were DNA extracted and investigated for the presence of HPV, and HPV-16 and its integration status, by polymerase chain reaction (PCR) and DNA sequencing.Results: Thirty-eight (72%) of the 53 paraffin-embedded OED samples, 16 (59%) of the 27 OSCC samples, and 12 (46%) of the 26 control samples were found to be HPV-DNA positive, with nested PCR (NPCR). Further, HPV-16 was detected in 31 (82%), 15 (94%), and 0 (0%) HPV-positive OED cases, HPV-positive OSCC cases, and controls, respectively. Integration was observed in 26/31 (84%) and 13/15 (87%) of the HPV-16-positive OED and OSCC cases, respectively. A statistically significant difference was found comparing prevalence of HPV-16 in controls with that in both OED and OSCC samples (P<0.005). A statistically significant difference was also found comparing prevalence of integrated and episomal viral forms comparing OED and OSCC samples (P<0.005).Conclusion: The high prevalence of HPV and high-risk HPV-16 in OED and OSCC samples suggests a potential aetiologic role for the virus in OSCC.
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19.
  • Jalouli, Miranda M., et al. (författare)
  • Differential Expression of Apoptosis, Cell Cycle Regulation and Intermediate Filament Genes in Oral Squamous Cell Carcinomas Associated with Toombak Use in Sudan
  • 2011
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 31:10, s. 3345-3351
  • Tidskriftsartikel (refereegranskat)abstract
    • Previously we used microarray genomic hybridization technology to explore genome-wide profiles of chromosomal aberrations in samples of oral squamous cell carcinomas (OSCCs) and paired normal controls. Based on these findings, 9 genes related to apoptosis, cell cycle regulation and intermediate filament proteins were selected and their differential expression status was examined by real-time quantitative RT-PCR in 26 samples of Sudanese OSCCs and their matched normal controls. The findings were correlated with the habit of toombak use. The mRNA levels of Bcl2, keratin 1, keratin 13 and p53 were significantly lower and the level of survivin was significantly higher in the OSCC samples of the toombak users compared to their paired control samples. A significant down-regulation in keratin I and keratin 13 expression levels was found in the OSCC samples of the non-toombak users compared to their normal control samples. The differential expression of genes related to apoptosis, cell cycle regulation and types I and II keratin could be useful diagnostic markers and provide valuable information for the understanding of oral malignancy in relation to toombak use.
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20.
  • Meyer, Simon, et al. (författare)
  • A simple, effective, universal, and reusable osteotomy tool for jaw reconstructions with microvascular fibula transplants
  • 2020
  • Ingår i: Journal of plastic, reconstructive & aesthetic surgery : JPRAS. - : Elsevier BV. - 1878-0539 .- 1748-6815. ; 73:1, s. 98-102
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Precise, expensive individual saw guides are used with increasing frequency for the reconstruction of mandibular defects with fibular grafts. In this report, an alternative is presented - the Multiuse Cutting Jig (MUC-Jig, proprietary development). It is reusable, suitable for all patients, requires simple planning based on conventional CT imaging, and is more economical.METHODS: To investigate its precision, we conducted a nonblinded experimental study, with ten participating craniomaxillofacial surgeons. Osteotomies of four different fibula segments were carried out at the same angulation, with groups defined according to the proximal and distal fixed angulation: 45°, 30°, 15°, or 0°. The sagittal cut was performed proximally, with the coronal cut performed distally. The resulting 40 segments (n = 40) were analyzed with their Tx length (primary endpoint) and osteotomy angles, and compared to the original planning.RESULTS: The mean (SD) relative deviation of all grafts from the original planning was -0.08 mm (1.12) in length and -0.71° (3.15) for the angle. Only 45° (-2.04 ± 3.71°) and 30° (-1.07 ± 2.52°) cuts differed significantly (p < 0.05) from smaller angle grafts. The mean (SD) absolute deviation was 0.81 mm (0.27) in length and 2.13° (0.93) in graft angles. For individual transplants, 45° cuts (1.28 ± 1.03 mm) differed significantly (p < 0.005) from others. We observed no differences in relative length or absolute angle deviation.CONCLUSIONS: The MUC-Jig is precise and cost-effective for osteotomies with medium angles and smooth reconstructions of template-guided procedures.
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21.
  • Runow Stark, Christina, et al. (författare)
  • Brush Biopsy For HR-HPV Detection With FTA Card And AI For Cytology Analysis - A Viable Non-invasive Alternative
  • 2018
  • Ingår i: EAOM2018.
  • Konferensbidrag (refereegranskat)abstract
    • Introduction: Oral cancer accounts for about 800-1,000 new cases each year in Sweden and the ratio of cancer related to high-risk human papillomavirus (HR-HPV) is increasing in the younger population due to changes in sexual habits. The most two frequent HR-HPV types 16 and 18 have both significant oncogenic potential.Objectives: In this pilot study we evaluate two non-invasive automated methods; 1) detection of HR-HPV using FTA cards, and 2) image scanning of cytology for detection of premalignant lesions as well as eradicate the early stage of neoplasia.Material and Methods: 160 patients with verified HR-HPV oropharyngeal cancer, previous ano-genital HR-HPV-infection or potentially malignant oral disorder were recruited for non-invasive brush sampling and analyzed with two validated automated methods both used in cervix cancer screening. For analysis of HR-HPV DNA the indicating FTA elute micro cardTM were used for dry collection, transportation and storage of the brush samples. For analysis of cell morphology changes an automated liquid base Cytology method (Preserve Cyt) combined with deep learning computer aided technique was used.Results: Preliminary results show that the FTA-method is reliable and indicates that healthy and malignant brush samples can be separated by image analysis. Conclusions: With further development of these fully automated methods, it is possible to implement a National Screening Program of the oral mucosa, and thereby select patients for further investigation in order to find lesions with potential malignancy in an early stage. 
  •  
22.
  • Beniczky, Sándor, et al. (författare)
  • Standardized computer-based organized reporting of EEG : SCORE - Second version
  • 2017
  • Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457. ; 128:11, s. 2334-2346
  • Tidskriftsartikel (refereegranskat)abstract
    • Standardized terminology for computer-based assessment and reporting of EEG has been previously developed in Europe. The International Federation of Clinical Neurophysiology established a taskforce in 2013 to develop this further, and to reach international consensus. This work resulted in the second, revised version of SCORE (Standardized Computer-based Organized Reporting of EEG), which is presented in this paper. The revised terminology was implemented in a software package (SCORE EEG), which was tested in clinical practice on 12,160 EEG recordings. Standardized terms implemented in SCORE are used to report the features of clinical relevance, extracted while assessing the EEGs. Selection of the terms is context sensitive: initial choices determine the subsequently presented sets of additional choices. This process automatically generates a report and feeds these features into a database. In the end, the diagnostic significance is scored, using a standardized list of terms. SCORE has specific modules for scoring seizures (including seizure semiology and ictal EEG patterns), neonatal recordings (including features specific for this age group), and for Critical Care EEG Terminology. SCORE is a useful clinical tool, with potential impact on clinical care, quality assurance, data-sharing, research and education.
  •  
23.
  • Blomqvist, G, et al. (författare)
  • Association between development of lower lip cancer and tobacco habits
  • 1991
  • Ingår i: Journal of oral and maxillofacial surgery (Print). - : Elsevier BV. - 0278-2391 .- 1531-5053. ; 49:10, s. 1044-1047; discussion 1048
  • Tidskriftsartikel (refereegranskat)abstract
    • Tobacco use is considered to increase the risk of tumor induction. The purpose of this case-controlled investigation was to assess the association of tobacco habits and development of squamous cell carcinoma of the lower lip. Sixty-one patients treated for lower lip cancer, aged between 42 and 90 years, were studied. Age- and sex-matched healthy controls showed a similar exposure to tobacco in years and a comparable distribution of tobacco habits. Although the mean exposure factor (duration times exposure) was greater in the tumor group, no intimate correlation between lip cancer and tobacco was demonstrated. However, an increased, although small, occurrence of herpes labialis lesions was found in cancer patients. The hypothesis is presented that smokers experiencing recurrent herpes simplex virus 1 (HSV-1) infections are more liable to tumor initiation, which issue will be subjected to a future study.
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24.
  •  
25.
  • Cesaro, Simone, et al. (författare)
  • Cidofovir for BK Virus-Associated Hemorrhagic Cystitis: A Retrospective Study
  • 2009
  • Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 49:2, s. 233-240
  • Tidskriftsartikel (refereegranskat)abstract
    • Background. BK virus-associated hemorrhagic cystitis (BKV-HC) is a severe complication after allogeneic hematopoietic stem cell transplantation (HSCT), but antiviral treatment for this condition has not been evaluated. Methods. We conducted a retrospective survey on the safety and outcome of cidofovir treatment for patients with BKV-HC in centers affiliated with the European Group for Blood and Marrow Transplantation. Results. From 1 April 2004 to 31 December 2007, 62 patients received a diagnosis of BKV-HC after a median interval of 35 days after HSCT (range, 3-577 days). Fifty-seven patients (92%) received intravenous cidofovir, whereas 5 patients received cidofovir intravesically. Complete response (CR) was recorded in 38 (67%) of 57 patients with HC treated with intravenous cidofovir, whereas partial response (PR) was documented in 7 patients (12%). CR was documented in 3 patients and PR in 1 patient with HC treated with intravesical cidofovir. A reduction of 1-3 logs in BKV load was documented in 8 of the 10 patients achieving CR. Mild-to-moderate toxic effects were recorded in 18 of 57 patients who received intravenous cidofovir administration. In a multivariate analysis, the factors significantly associated with response to cidofovir were the stem cell source (Pp. 01) and the use of total body irradiation (P = .03). After a median follow-up of 287 days, overall survival and total treatment-related mortality rates were 63% and 40% for patients achieving CR, compared with 14% and 72% for patients with PR or no response to cidofovir, respectively (P < .001 and P = .001, respectively). Conclusions. Cidofovir may be a potentially effective therapy for BKV-HC, but evidence supporting its use requires randomized controlled trials.
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26.
  • Dérand, Per, et al. (författare)
  • Imaging, virtual planning, design and production of patient specific implants and clinical validation in cranio-maxillo-facial surgery
  • 2012
  • Ingår i: Cranial maxillofacial Trauma and Reconstruction. - : SAGE Publications. - 1943-3875 .- 1943-3883. ; 5:3, s. 137-144
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this article was to describe the workflow from imaging, via virtual design, to manufacturing of patient-specific titanium reconstruction plates, cutting guide and mesh, and its utility in connection with surgical treatment of acquired bone defects in the mandible using additive manufacturing by electron beam melting (EBM). Based on computed tomography scans, polygon skulls were created. Following that virtual treatment plans entailing free microvascular transfer of fibula flaps using patient-specific reconstruction plates, mesh, and cutting guides were designed. The design was based on the specification of a Compact UniLOCK 2.4 Large (Synthes®, Switzerland). The obtained polygon plates were bent virtually round the reconstructed mandibles. Next, the resections of the mandibles were planned virtually. A cutting guide was outlined to facilitate resection, as well as plates and titanium mesh for insertion of bone or bone substitutes. Polygon plates and meshes were converted to stereolithography format and used in the software Magics for preparation of input files for the successive step, additive manufacturing. EBM was used to manufacture the customized implants in a biocompatible titanium grade, Ti6Al4V ELI. The implants and the cutting guide were cleaned and sterilized, then transferred to the operating theater, and applied during surgery. Commercially available software programs are sufficient in order to virtually plan for production of patient-specific implants. Furthermore, EBM-produced implants are fully usable under clinical conditions in reconstruction of acquired defects in the mandible. A good compliance between the treatment plan and the fit was demonstrated during operation. Within the constraints of this article, the authors describe a workflow for production of patient-specific implants, using EBM manufacturing. Titanium cutting guides, reconstruction plates for fixation of microvascular transfer of osteomyocutaneous bone grafts, and mesh to replace resected bone that can function as a carrier for bone or bone substitutes were designed and tested during reconstructive maxillofacial surgery. A clinically fit, well within the requirements for what is needed and obtained using traditional free hand bending of commercially available devices, or even higher precision, was demonstrated in ablative surgery in four patients.
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27.
  • Ekstrand, Karl, et al. (författare)
  • Malignant tumors of the maxilla : virtual planning and real-time rehabilitation with custom-made R-zygoma fixtures and carbon-graphite fiber-reinforced polymer prosthesis
  • 2008
  • Ingår i: Clinical Implant Dentistry and Related Research. - : Wiley. - 1523-0899 .- 1708-8208. ; 10:1, s. 23-29
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Oral cancer is a mutilating disease. Because of the expanding application of computer technology in medicine, new methods are constantly evolving. This project leads into a new technology in maxillofacial reconstructive therapy using a redesigned zygoma fixture. PURPOSE: Previous development experiences showed that the procedure was time-consuming and painful for the patients. Frequent episodes of sedation or general anesthetics were required and the rehabilitation is costly. The aim of our new treatment goal was to allow the patients to wake up after tumor surgery with a functional rehabilitation in place. MATERIALS AND METHODS: Stereolithographic models were introduced to produce a model from the three-dimensional computed tomography (CT). A guide with the proposed resection was fabricated, and the real-time maxillectomy was performed. From the postoperative CT, a second stereolithographic model was manufactured and in addition, a stent for the optimal position of the implants. Customized zygoma implants were installed (R-zygoma, Integration AB, Göteborg, Sweden). A fixed construction was fabricated by using a new material based on poly(methylacrylate) reinforced with carbon/graphite fibers and attached to the implants. On the same master cast, a separate obturator was fabricated in permanent soft silicon. RESULTS: The result of this project showed that it was possible to create a virtual plan preoperatively to apply during surgery in order for the patient to wake up functionally rehabilitated. CONCLUSION: From a quality-of-life perspective, it is an advantage to be rehabilitated fast. By using new computer technology, pain and discomfort are less and the total rehabilitation is faster, which in turn reduces days in hospital and thereby total costs.
  •  
28.
  • Hedner, E, et al. (författare)
  • Primary herpes simplex virus (type 1) infection delays healing of oral excisional and extraction wounds in the rat
  • 1990
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 19:10, s. 471-476
  • Tidskriftsartikel (refereegranskat)abstract
    • The effect of acute herpes simplex virus type 1 (HSV-1) infection on the healing process of intraoral wounds and tooth extraction sockets in the rat was studied. A standardized size of the buccal mucosa was excised and molars were extracted and a HSV-1 suspension was topically applied. The virus infected wounds were clinically characterized by erythema and swelling and histologically by heavy inflammation cell infiltrate and abscesses during the first week. The acute HSV-1 infection was found to significantly delay healing of both types of wounds by 3 days. Antiviral treatment with acyclovir (ACV) decreased the degree of inflammation and improved healing of the infected wounds. The present results indicate a delayed and disturbed healing of wounds in the oral cavity in the presence of HSV-1. The findings may have a clinical significance for primary or latent HSV-1 infections in conjunction with surgical intervention in the oral cavity.
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29.
  • Hedner, E, et al. (författare)
  • Reactivated herpes simplex virus infection as a possible cause of dry socket after tooth extraction
  • 1993
  • Ingår i: Journal of oral and maxillofacial surgery (Print). - 0278-2391 .- 1531-5053. ; 51:4, s. 370-376; discussion 377
  • Tidskriftsartikel (refereegranskat)abstract
    • This study was designed to evaluate a possible association between reactivated herpes simplex virus type 1 (HSV-1) infection after lower third molar extraction and development of dry socket (DS). The HSV-1 antibody response was analyzed before and after tooth removal by enzyme-linked immunosorbent assay and immunoblotting in 208 patients. History of previous possible oral herpes reactivation was evaluated by a questionnaire that was based on self-rated frequency of oral cold sores. Tobacco users were identified. The anatomic proximity of the root apex to the mandibular nerve canal was classified radiographically before extraction. Fifteen patients (7%) developed DS after tooth extraction. Eleven of the 15 DS patients (73%) were HSV seropositive as compared with 7 of 15 (47%) in the matched control group. Seven of the 11 seropositive DS patients have shown HSV-1 reactivation by an increase of specific polypeptides, predominantly gB, gC, gD and ICP 4 and 6, in the immunoblot test. No change in HSV-1 reactivity was observed in control sera. DS patients reported a high frequency of oral cold sores (64%) compared with the controls (33%). Tobacco use was not found to influence the frequency of cold sores or the development of DS. A close radiographic proximity between the mandibular canal and root apex was more common (P < .05) in DS patients. The results indicate that extraction of a mandibular third molar could be a possible cause of reactivation and recurrence of an HSV-1 infection. The serum antibody response, the anatomical nerve/root proximity, and the history of oral cold sores reflect an association between HSV-1 and DS after tooth extraction.
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30.
  • Hedner, E, et al. (författare)
  • Recrudescence of herpes simplex virus type 1 in latently infected rats after trauma to oral tissues
  • 1993
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 22:5, s. 214-220
  • Tidskriftsartikel (refereegranskat)abstract
    • Tooth extraction in rats was used to trigger a latent HSV-1 infection. HSV-1 was inoculated unilaterally in the rat palates. Eight weeks later two molars were removed bilaterally. The trigeminal ganglia were co-cultivated and HSV-1 was isolated from 63% of the ganglia on the infected sides but from only 11% on control sides. The immune response pattern was analysed by immunoblotting of rat serum, and strong reactivity to HSV-1 specific cell polypeptides and glycoproteins (ICP6, gC, pgC, gD) was seen after reactivation. The extraction sockets were histopathologically evaluated and showed healing on the infected side in 26% compared to 63% in contralateral control sockets. The effect of acyclovir (ACV) treatment was elucidated and was found to influence the subsequent development of antibodies and to promote healing of the sockets. Vesiculation in intra- and subepithelial tissue was present on the infected side in 58% but in only 12% of ACV-treated animals. The present study in rats has shown that a latent HSV-1 infection can be established and reactivated by tooth extraction. Reactivation resulted in delayed healing of sockets on the latently infected side but not on the contralateral control side. HSV-1 reactivation was demonstrated serologically by immunoblotting. Healing was significantly promoted by administration of ACV, which also supports the contention that HSV-1 interferes with the healing process.
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31.
  • Hillbertz, Nicolette Salmon, et al. (författare)
  • Viral and Molecular Aspects of Oral Cancer
  • 2012
  • Ingår i: Anticancer Research. - 0250-7005 .- 1791-7530. ; 32:10, s. 4201-4212
  • Forskningsöversikt (refereegranskat)abstract
    • Squamous cell carcinoma (SCC) is the most common epithelial malignancy in the oral cavity. SCCs and their variants constitute over 90% of oral malignancies, and the disease is associated with poor prognosis. OSCC is a complex malignancy where environmental factors, virus infections, and genetic alterations most likely interact, and thus give rise to the malignant condition. Herein, we review the available literature regarding high-risk factors such as alcohol and tobacco usage; discuss the roles of human papillomaviruses (HPV), the Epstein-Barr virus, and the human herpes simplex virus (HSV); and evaluate several candidate genes associated with the condition: p53, p16(INK4) and p21(WAF1/CIP1) survivin, B-cell lymphoma-2 (BCL-2), keratins, Fibroblast growth factor 3 (FGF3), FGF4, FGF19, Oral cancer overexpressed gene 1 (ORAOV1), and Cyclin D1 (CCND1).
  •  
32.
  • Hirsch, Jan M, et al. (författare)
  • A clinical, histomorphological and histochemical study on snuff-induced lesions of varying severity
  • 1982
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 11:5, s. 387-398
  • Tidskriftsartikel (refereegranskat)abstract
    • The oral lesions in 50 habitual snuff-dippers were graded on a four-point scale. The patients' tobacco and drinking habits were studied by means of a questionnaire. From each patient a biopsy was taken for histomorphological and histochemical analysis. A correlation between snuff habits and the clinical degrees was found, as well as between the snuff habits and certain superficial and deeply located cell changes. The incidence of keratinized lesions, sialadenitis and slight dysplasia (based on subjective evaluation under a light microscope) was higher than previously reported. Presence of dysplastic changes could not be predicted by means of the parameters which characterise the snuff habit or from the clinical grade. The histomorphological and histochemical results were interpreted as showing that the mucosa react to snuff inducing hyperplasia in the basal cell layers. In the surface layer indications of lethal damage were found. The overall stromal reaction to snuff was weak. However, the salivary glands and excretory ducts exhibited degenerative changes which were found to be more severe than the pathological changes in the surface epithelium.
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33.
  • Hirsch, Jan M, et al. (författare)
  • Effect of long-term application of snuff on the oral mucosa : an experimental study in the rat
  • 1983
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 12:3, s. 187-198
  • Tidskriftsartikel (refereegranskat)abstract
    • The long-term effect of snuff exposure was studied in Sprague-Dawley rats using a surgically-created test canal in the lower lip to retain snuff. The rats received standard snuff (n = 42) and highly alkaline snuff (n = 10) for 9-22 months, whereupon they were killed. Untreated rats with identical test canals (n = 15) served as controls. A complete post-mortem examination was performed. One rat exposed to standard snuff for 9 months developed a squamous cell carcinoma of the oral cavity. However, exposure to standard snuff usually resulted in a mild to moderate hyperplasia of the epithelium, hyperorthokeratosis and acanthosis. Rats exposed to snuff for 18-22 months showed vacuolated cells penetrating deeper into the epithelium with hyperplastic and atrophic lesions. In a few rats, severe dysplastic changes developed in the crevicular epithelium. Rats exposed to alkaline snuff differed little from the first group except that there was focally atrophic and ulcerated epithelium and less fibrosis. Pathological findings outside the oral cavity were rare. Squamous cell hyperplasia of the forestomach was found in rats exposed to snuff for 18-22 months, possibly caused by ingested snuff. In conclusion, this study has shown that exposure of rats to snuff for 10-16 hours per day 5 days a week for most of their life-span resulted in lesions mainly restricted to the epithelium and the underlying connective tissue of the surgically created test canal.
  •  
34.
  • Hirsch, Jan M, et al. (författare)
  • Fixture stability and nerve function after transposition and lateralization of the inferior alveolar nerve and fixture installation
  • 1995
  • Ingår i: British Journal of Oral & Maxillofacial Surgery. - : Elsevier BV. - 0266-4356 .- 1532-1940. ; 33:5, s. 276-281
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty-four posterior mandibular segments in 18 patients were operated on placing implants after mobilisation of the neurovascular bundle. Two different surgical techniques, transposition and lateralization was used. The overall survival rate of fixtures was 92.1%. Performing lateralization resulted in 100% success, while transposition resulted in 80% stable fixtures in the involved segments. The mean time to full restoration of nerve function was 3.8 weeks after lateralization and 5.7 weeks after tranposing the nerve. Three patients exhibited persisting slight hyposthesia, but all, subjectively negligible disturbances in nerve function.
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35.
  • Hirsch, Jan M, et al. (författare)
  • Hemodynamic effects of the use of oral snuff
  • 1992
  • Ingår i: Clinical Pharmacology and Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 52:4, s. 394-401
  • Tidskriftsartikel (refereegranskat)abstract
    • The hemodynamic effects during rest and exercise of oral snuff were investigated in an open, placebo-controlled study of nine habitual users of oral snuff. Blood pressure, heart rate, and central hemodynamics were measured noninvasively. Plasma concentrations of nicotine, cotinine, norepinephrine, and epinephrine, as well as neuropeptide Y-like immunoreactivity were measured before and after snuff intake during rest and exercise. Snuff intake induced a significant increase in heart rate and blood pressure and a decrease in stroke volume during rest. Hemodynamic changes were unrelated to nicotine or cotinine concentrations. Resting levels of norepinephrine and neuropeptide Y-like immunoreactivity were similar with or without snuff, whereas epinephrine was slightly increased 30 minutes after snuff intake. The exercise-induced increase in norepinephrine and neuropeptide Y-like immunoreactivity did not differ between the days subjects received snuff and the days they received placebo. In contrast, maximum work load was associated with a slight increase in circulating epinephrine after snuff intake. The findings suggest that snuff intake is associated with significant hemodynamic effects during rest but not during exercise. These effects could not be readily explained by activation of the sympathetic nervous system.
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36.
  • Hirsch, Jan M, et al. (författare)
  • Inhibition of herpes simplex virus replication by tobacco extracts
  • 1984
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 44:5, s. 1991-1997
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex virus type 1 (HSV-1) has been associated with the genesis of leukoplakias, epithelial atypia, and oral cancer. Tobacco habits, such as snuff dipping, are also definitely correlated with this type of lesion. The normal cytolytic HSV-1 infection can, after in vitro inactivation, transform cells. Extracts of snuff were prepared and assayed for their ability to inhibit HSV-1 replication. Plaque formation assays of HSV-1 in the presence of snuff extract showed that a reduced number of plaques was formed. Different batches of one brand of snuff were tested for inhibition of herpes simplex virus (HSV) production. More than 99% inhibition of 24-hr HSV production was obtained with undiluted batches. The 1:5 dilutions of snuff had an inhibitory effect of 85% and 1:25 dilutions, 39%. In agreement, the attachment of the virus to the host cell and penetration of the virus to the cell nuclei were found to be inhibited as was the synthesis of viral DNA. Nicotine had an inhibitory effect, while aromatic additions to snuff were found to have no major inhibitory effect on HSV replication. Snuff extracts were prepared from different brands of snuff reported to contain high and low quantities of tobacco-specific N-nitrosamines. Brands with reported high levels of tobacco-specific N-nitrosamines had significantly greater ability to inhibit HSV replication. In conclusion, this study has shown that extracts of snuff have inhibitory effects on the production of cytolytic HSV-1 infections. A chronic snuff dipper keeps tobacco in the mouth for the major part of the day. Thus, virus shed in the oral cavity in connection with a reactivated latent HSV-1 infection has great possibilities of being affected by snuff or derivatives of snuff. It is suggested that an interaction between tobacco products and HSV-1 might be involved in the development of dysplastic lesions in the oral cavity.
  •  
37.
  • Hirsch, Jan M, et al. (författare)
  • Maxillary sinus augmentation using mandibular bone grafts and simultaneous installation of implants : A surgical technique
  • 1991
  • Ingår i: Clinical Oral Implants Research. - : Wiley. - 0905-7161 .- 1600-0501. ; 2:2, s. 91-96
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper presents a specific technique for maxillary sinus augmentation and simultaneous placement of implants in partially edentulous patients. In such patients, there is from time to time insufficient interarch distance for any type of onlay grafting. Health, non-smoking patients without previous or present sinus pathology, where the radiological and clinical examination revealed insufficient height and/or width of the remaining alveolar process in the posterior maxillary region, were selected. They were operated on using a mandibular bone graft obtained from the symphyseal region between the mental foramina and placed in the maxillary sinus. The recipient site was prepared by cutting in a rectangular shape the lateral sinus wall into the sinus lining. The bone wall was then separated towards the lateral nasal wall by rotating the inferior portion of the cut sinus wall medially. In the space thus created, the bone graft was placed. Fixtures were installed at the same session. The method described has proved to be uncomplicated to perform under local anesthesia and no major disadvantages for the patient or pre- or postoperative complications have so far been observed.
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38.
  • Hirsch, Jan M, et al. (författare)
  • Periapical surgery
  • 1979
  • Ingår i: International journal of oral surgery. - 0300-9785. ; 8:3, s. 173-185
  • Tidskriftsartikel (refereegranskat)abstract
    • A retrospective study of 572 teeth treated with periapical surgery was undertaken in order to evaluate the influence of preoperative, operative and postoperative factors in the healing process as well as the operation method used. It was also the aim to assess whether the histophatological diagnosis of biopsies taken at the operation could be correlated to healing. Statistical analyses by the AID method and conventional cross-classification methods were performed. Factors of importance were found to be the extent of the destrucion, the operation method used, the bone surrounding the destruction, the quality of the orthograde root filling, the age of the patient, and the marginal bone buccally. The operation method was of importance in large destructions where root fillings were considered as not having properly sealed the canals, and when treating inflamed cysts. The histopathological diagnosis could not be ascribed any definite prognostic value.
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39.
  • Hirsch, Jan M, et al. (författare)
  • Snuff-induced lesions of the oral mucosa : an experimental model in the rat
  • 1981
  • Ingår i: Journal of oral pathology. - 0300-9777. ; 10:5, s. 342-353
  • Tidskriftsartikel (refereegranskat)abstract
    • An experimental model in the white rat has been developed in order to study the influence of snuff on oral mucosa. A test canal in the lower lip, with one orifice buccally to the incisors and one on the lip side, was created by surgical means. The connection between the canal and the oral cavity was made to ensure the presence of saliva in the canal so that physiological conditions resembling those of the oral cavity were obtained. The canal was filled with snuff morning and night 5 days a week. The mean value for the maximal retention time of the snuff was 6 h. The animals tolerated the dose and time of exposure without signs of severe toxic symptoms. Histological examination of the canals after 9 months of exposure to snuff showed a mildly to moderately hyperplastic epithelium with hyperorthokeratosis. Locally deep proliferations of epithelium with acanthotic rete pegs could be seen. In the stratum basale hyperplasia with disturbed polarity and hyperchromatic nuclei and single mitosis were noted.
  •  
40.
  • Hirsch, Jan M, et al. (författare)
  • The reversibility of the snuff-induced lesion : an experimental study in the rat
  • 1986
  • Ingår i: Journal of Oral Pathology & Medicine. - : Wiley. - 0904-2512 .- 1600-0714. ; 15:10, s. 540-543
  • Tidskriftsartikel (refereegranskat)abstract
    • Snuff lesions were induced in 30 rats. Ten of the snuff-exposed rats were killed immediately after 13 months snuff exposure, as were the 10 control animals. Ten rats were killed 1 month and 10 rats 4 months after the snuff administration had ceased. The rats exposed to snuff for 13 months exhibited hyperplastic, hyperorthokeratotic epithelium with focal mild atypia, focal ulcerations and marked subepithelial fibrosis. These changes were markedly reduced or absent in rats exposed to snuff and killed after a snuff-free interval of 1 or 4 months. Similar differences between the test-groups were seen in the epithelium lining the gingival sulcus of the lower incisors. This area seems to be more sensitive to chemical exposure than the oral mucosa proper as more severe microscopical changes were seen here. Snuff exposure results in the development of a hyperplastic, reactive, reversible lesion of the oral mucosa, suggesting that snuff predominantly has promoting activity when administered for a relatively short interval of time.
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41.
  • Hirsch, Jan M, et al. (författare)
  • Tobacco habits among teenagers in the city of Göteborg, Sweden, and possible association with dental caries.
  • 1991
  • Ingår i: Swedish dental journal. - 0347-9994. ; 15:3, s. 117-23
  • Tidskriftsartikel (refereegranskat)abstract
    • Frome nine dental clinics within the Public Dental Service in the City of Göteborg, 2145 patients aged 14 to 19 answered a questionnaire concerning their tobacco habits. Tobacco was used in some form by 27 per cent of the patients and use increased with age. Smoking was more common among girls than among boys: 24 and 12 per cent, respectively. The statistical analyses showed that smoking as a habit and an increased number of cigarettes smoked per day are positively correlated with increases in the number of decayed, missing and filled teeth and the number of initially decayed proximal surfaces. Further, all caries epidemiological data were significantly higher among patients with tobacco habits compared to non-users. It can be concluded that there is a correlation between the tobacco habit and increased caries prevalence. However, dietary and oral habits have to be further elucidated before any definite conclusions can be made regarding the effect of the tobacco habit per se on the development of caries.
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42.
  •  
43.
  • Huo, Jinxing, 1987-, et al. (författare)
  • Analytical Study of Stress Distributions around Screws in Flat Mandibular Bone under In-Plane Loading
  • 2023
  • Ingår i: Bioengineering. - : MDPI AG. - 2306-5354. ; 10:7
  • Tidskriftsartikel (refereegranskat)abstract
    • A known complication for mechanically loaded bone implants is the instability due to screw loosening, resulting in infection and the non-union of fractures. To investigate and eventually prevent such bone degradation, it is useful to know the stress state in the bone around the screw. Considering only in-plane loadings and simplifying the mandibular bone into an orthotropic laminated plate, the analysis was reduced to a two-dimensional pin-loaded plate problem. An analytic model, based on the complex stress analysis, was introduced to the bone biomechanics field to obtain the stress distributions around the screw hole in the bone. The dimensionless normalized stresses were found to be relatively insensitive to the locations of the screw hole over the mandible. Parametric analyses were carried out regarding the friction coefficient and load direction. It was found that the load direction had a negligible influence. On the contrary, the friction coefficient had a significant effect on the stress distributions. Whether the screw was well bonded or not thus played an important role. The proposed analytic model could potentially be used to study bone failure together with stress-based failure criteria.
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44.
  • Jalouli, Miranda, et al. (författare)
  • Nested PCR for detection of HSV-1 in oral mucosa
  • 2015
  • Ingår i: Medicina Oral, Patologia Oral y Cirugia Bucal. - : Medicina Oral, S.L.. - 1698-4447 .- 1698-6946. ; 20:6
  • Tidskriftsartikel (refereegranskat)abstract
    • © Medicina Oral S. L. Background: It has been estimated that 15%-20% of human tumours are driven by infection and inflammation, and viral infections play an important role in malignant transformation. The evidence that herpes simplex virus type 1 (HSV-1) could be involved in the aetiology of oral cancer varies from weak to persuasive. This study aimed to investigate by nested PCR (NPCR) the prevalence of HSV-1 in samples from normal oral mucosa, oral leukoplakia, and oral squamous cell carcinoma (OSCC). Material and Methods: We investigated the prevalence of HSV-1 in biopsies obtained from 26 fresh, normal oral mucosa from healthy volunteers as well as 53 oral leukoplakia and 27 OSCC paraffin-embedded samples. DNA was extracted from the specimens and investigated for the presence of HSV-1 by nested polymerase chain reaction (NPCR) and DNA sequencing. Results: HSV-1 was detected in 14 (54%) of the healthy samples, in 19 (36%) of the oral leukoplakia samples, and in 14 (52%) of the OSCC samples. The differences were not statistically significant. Conclusions: We observed a high incidence of HSV-1 in healthy oral mucosa, oral leukoplakia, and OSCC tissues. Thus, no connection between OSCC development and presence of HSV-1 was detected.
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45.
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46.
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47.
  • Johansson, S L, et al. (författare)
  • Snuff-induced carcinogenesis : effect of snuff in rats initiated with 4-nitroquinoline N-oxide
  • 1989
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 49:11, s. 3063-3069
  • Tidskriftsartikel (refereegranskat)abstract
    • A canal in the lower lip to function as a reservoir for snuff was surgically created in 150 male Sprague-Dawley rats. The animals were randomized into five groups of 30 each: Group I received snuff twice a day, 5 days a wk; Group II was painted with propylene glycol (solvent control) on the hard palate 3 times a wk during 4 wk; Group III underwent painting on the hard palate with 4-nitroquinoline N-oxide (4-NQO) dissolved in propylene glycol, 3 times a wk for 4 wk; Group IV received 4-NQO as in Group III followed by snuff application as in Group I; and Group V received a cotton pellet dipped in saline twice a day, 5 days a wk. Treatment continued for up to 108 wk. There was no significant difference in mean survival time between the groups. Squamous cell tumors of the lip, oral and nasal cavities, esophagus, and forestomach were seen only in Groups I, III, and IV. Nine tumors of these organs were found in Group I (six carcinomas and three papillomas), nine in Group III (seven carcinomas and two papillomas), and ten in Group IV (eight carcinomas and two papillomas). The difference between each of these groups and the control groups (II and V) with regard to tumor incidence is statistically significant (P less than 0.05). In Group I, four oral cavity or lip carcinomas were found in 29 rats, a significant difference in relation to control rats (P less than 0.05). In addition, hyperplastic lesions of the lip, palate, and forestomach were significantly more common in Groups I and IV compared with Groups II, III, and V. The study has shown that snuff and 4-NQO by themselves have the potential to induce malignant tumors. Initiation with 4-NQO followed by snuff did not significantly enhance tumor formation.
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48.
  • Kim, HyeJin, et al. (författare)
  • Towards a better future for biodiversity and people : Modelling Nature Futures
  • 2023
  • Ingår i: Global Environmental Change. - 0959-3780 .- 1872-9495. ; 82
  • Tidskriftsartikel (refereegranskat)abstract
    • The Nature Futures Framework (NFF) is a heuristic tool for co-creating positive futures for nature and people. It seeks to open up a diversity of futures through mainly three value perspectives on nature - Nature for Nature, Nature for Society, and Nature as Culture. This paper describes how the NFF can be applied in modelling to support decision-making. First, we describe key considerations for the NFF in developing qualitative and quantitative scenarios: i) multiple value perspectives on nature as a state space where pathways improving nature toward a frontier can be represented, ii) mutually reinforcing key feedbacks of social-ecological systems that are important for nature conservation and human wellbeing, iii) indicators of multiple knowledge systems describing the evolution of complex social-ecological dynamics. We then present three approaches to modelling Nature Futures scenarios in the review, screening, and design phases of policy processes. This paper seeks to facilitate the integration of relational values of nature in models and strengthen modelled linkages across biodiversity, nature's contributions to people, and quality of life.
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49.
  • Koriakina, Nadezhda, 1991-, et al. (författare)
  • Visualization of convolutional neural network class activations in automated oral cancer detection for interpretation of malignancy associated changes
  • 2019
  • Ingår i: 3rd NEUBIAS Conference, Luxembourg, 2-8 February 2019.
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Introduction: Cancer of the oral cavity is one of the most common malignancies in the world. The incidence of oral cavity and oropharyngeal cancer is increasing among young people. It is noteworthy that the oral cavity can be relatively easily accessed for routine screening tests that could potentially decrease the incidence of oral cancer. Automated deep learning computer aided methods show promising ability for detection of subtle precancerous changes at a very early stage, also when visual examination is less effective. Although the biological nature of these malignancy associated changes is not fully understood, the consistency of morphology and textural changes within a cell dataset could shed light on the premalignant state. In this study, we are aiming to increase understanding of this phenomenon by exploring and visualizing what parts of cell images are considered as most important when trained deep convolutional neural networks (DCNNs) are used to differentiate cytological images into normal and abnormal classes.Materials and methods: Cell samples are collected with a brush at areas of interest in the oral cavity and stained according to standard PAP procedures. Digital images from the slides are acquired with a 0.32 micron pixel size in greyscale format (570 nm bandpass filter). Cell nuclei are manually selected in the images and a small region is cropped around each nucleus resulting in images of 80x80 pixels. Medical knowledge is not used for choosing the cells but they are just randomly selected from the glass; for the learning process we are only providing ground truth on the patient level and not on the cell level. Overall, 10274 images of cell nuclei and the surrounding region are used to train state-of-the-art DCNNs to distinguish between cells from healthy persons and persons with precancerous lesions. Data augmentation through 90 degrees rotations and mirroring is applied to the datasets. Different approaches for class activation mapping and related methods are utilized to determine what image regions and feature maps are responsible for the relevant class differentiation.Results and Discussion:The best performing of the observed deep learning architectures reaches a per cell classification accuracy surpassing 80% on the observed material. Visualizing the class activation maps confirms our expectation that the network is able to learn to focus on specific relevant parts of the sample regions. We compare and evaluate our findings related to detected discriminative regions with the subjective judgements of a trained cytotechnologist. We believe that this effort on improving understanding of decision criteria used by machine and human leads to increased understanding of malignancy associated changes and also improves robustness and reliability of the automated malignancy detection procedure.
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50.
  • Korytowska, M., et al. (författare)
  • Patient-reported pain after surgical removal of leukoplakia - an observational 1-year follow-up study
  • 2021
  • Ingår i: Acta Odontologica Scandinavica. - : Informa UK Limited. - 0001-6357 .- 1502-3850. ; 79:5, s. 383-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Oral leukoplakia (OL) presents as a white lesion of the oral mucosa and is not typically associated with the sensation of pain. OL should be surgically removed when possible because it is considered a potentially malignant oral disorder (PMOD). This study assessed the pain sensations experienced by patients in association with the occurrence and surgical treatment of OL. Methods: Inclusion criteria were: a clinical diagnosis of OL; biopsy excision; and observation for at least 12 months in the ORA-LEU-CAN study. At the first visit, all the patients were asked about the occurrence of symptoms within the lesion. Ninety-four subjects were assessed over a period of 1 year. All patients underwent complete removal of OL. The patient cohort was divided into three sub-groups: (i) no pain before excision and at the 1-year follow-up; (ii) pain before excision; and (iii) pain at the 1-year follow-up. Results: Overall, pain was reported by 21.3% of the patients at the study start whereas 13.8% of the patients reported pain 1 year after surgical treatment. Patient-reported pain from the lesion at study inclusion was significantly associated with lesions found on the lateral side of the tongue (p=.002). Pain reported by patients one year after surgery was significantly related to female gender (p=.038) and the presence of epithelial cell dysplasia (p=.022). Conclusion: We conclude that surgical removal of OL results in a low risk of long-term post-surgical pain. However, OL located on the lateral side of the tongue and in OL with dysplasia are more likely to be associated with pain.
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