Long-term side effects on the temporomandibular joints and oro-facial function in patients with obstructive sleep apnoea treated with a mandibular advancement device.

Patients with obstructive sleep apnoea (OSA) in long-term treatment with a mandibular advancement device (MAD) to increase the upper airway space may develop changes in the temporomandibular joint (TMJ) and the oro-facial function due to the protruded jaw position during sleep. The aim was to investigate the influence of long-term MAD treatment on the TMJs, oro-facial function and occlusion. This prospective study included 30 men and 13 women (median age 54) with OSA [Apnoea-Hypopnoea Index (AHI): 7-57]. They were examined with the Nordic Orofacial Test Screening (NOT-S), the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) and cone beam computed tomography (CBCT) of the TMJs. The examination was performed before MAD treatment (T0), and 3-6 months (T1, no CBCT), 1 year (T2) and 3 years (T3) after treatment start. The results were analysed as long term (T0-T3, n = 14) and short term (T0-T2, n = 24) by t-test, Fisher's exact test and anova. Both long- and short-term analyses revealed a reduction in AHI (P < 0·002). Significant long term were increased scores in the NOT-S Interview (P < 0·045), reduced vertical overbite (P < 0·031) and increased jaw protrusive movement (P < 0·027). TMJ changes were found as joint sounds in terms of reciprocal clicking and crepitus, short term as a decrease and subsequent recurrence (P < 0·053; P < 0·037). No significant radiological changes were found. In conclusion, MAD treatment is beneficial to some OSA patients, but might induce changes in the TMJs, the oro-facial function and the occlusion. However, these changes seemed to be less harmful than previously reported with careful adaptation, control and follow-ups.

Methicillin-resistant Staphylococcus aureus with mecC: a description of 45 human cases in southern Sweden.

In 2011, a novel mecA gene homologue, mecC, was reported in isolates from both humans and dairy cattle. The epidemiology of mecC methicillin-resistant Staphylococcus aureus (MRSA) in humans is not yet well known. In this retrospective study, we present the epidemiology of human clinical cases with mecC MRSA detected in the southern part of Sweden during the period 2005-2014. A total of 45 patients with an isolate positive for mecC MRSA were included in the study. Twenty-six isolates were found before 2012 and were retrospectively tested for mecC. Nineteen isolates were detected in 2012-2014 through routine testing. Culture results, resistance patterns, Panton-Valentine leukocidin (PVL) genes, and spa types were collected from the Clinical Microbiology Laboratory. Epidemiological data were received from the database at the Regional Centre for Communicable Disease Control and the patient's medical files. The majority of the patients with mecC MRSA were of Swedish origin, had underlying diseases, and lived in rural areas. The median age was 60 years. Of the mecC MRSA, 76 % belonged to spa types t373 and t843. The median minimum inhibitory concentration (MIC) value for oxacillin was 16 mg/L (1-64 mg/L) and only one isolate was resistant to other classes of antibiotics. The most common type of infection was skin and soft tissue infections, most often in an existing skin lesion. The patients with mecC MRSA were colonized for a short time and gave rise to few secondary cases. mecC MRSA in our region appears to have a domestic origin and mainly affects patients with underlying diseases or patients with an existing skin lesion. Our data indicate that it could be a poor colonizer.

Epidemiology of MRSA in southern Sweden: strong relation to foreign country of origin, health care abroad and foreign travel.

All notified MRSA cases in Skåne County have been followed since 2000. We have investigated the MRSA epidemiology over time, method of acquisition, whether some spa types are more prone to spread, and/or cause more infections, and the connection between spa type and country of acquisition/origin. All cases between 2000 and 2010 were included. Infection or colonization and the presence of PVL genes were noted. The spa types of the index cases were correlated with community or healthcare acquisition, proportion of MRSA-positive household contacts, country of origin of families and country of acquisition of MRSA. The number of cases increased from 31 in 2000 to 315 in 2010. Most cases were community-acquired and the median age was 30 years. Thirty-two per cent of the MRSA cases were found because of a clinical infection. Of the household contacts 35 % were MRSA-positive. Only 24 % of the MRSA cases were both of Swedish origin and had contracted MRSA in Sweden. An association between spa type and certain regions of acquisition/origin was noted. Spa types t044, t002 and t008 were the most predominant strains. PVL-positive spa types t008, t019 and t044 caused more skin infections than the other spa types. Our results support screening for MRSA in patients with health care contacts abroad, culturing of patients with skin infections contracted outside Sweden and performing contact tracing among household members. Knowledge of spa type might give guidance in the process of contact tracing. Eradication treatment of MRSA spa types causing more skin infections may be warranted.

Expanding the taxonomy of the diagnostic criteria for temporomandibular disorders.

There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus-based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long-term aim was to establish a foundation, vis-à-vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria.

Unusual increase of psittacosis in southern Sweden linked to wild bird exposure, January to April 2013.

Free-living wild birds worldwide act as reservoir for Chlamydia psittaci, but the risk of transmission to humans through contact with wild birds has not been widely documented. From 12 January to April 9 2013, a total of 25 cases of psittacosis were detected in southern Sweden, about a threefold increase compared with the mean of the previous 10 years. A matched case-control study investigating both domestic and wild bird exposure showed that cases were more likely than controls to have cleaned wild bird feeders or been exposed to wild bird droppings in other ways (OR: 10.1; 95% CI: 2.1-47.9). We recommend precautionary measures such as wetting bird feeders before cleaning them, to reduce the risk of transmission of C. psittaci when in contact with bird droppings. Furthermore, C. psittaci should be considered for inclusion in laboratory diagnostic routines when analysing samples from patients with atypical pneumonia, since our findings suggest that psittacosis is underdiagnosed.

The relationship between resonance frequency analysis (RFA) and lateral displacement of dental implants: an in vitro study.

This in vitro investigation was conducted to study the relationship between resonance frequency analysis (RFA) and lateral displacement measurements of dental implants. A total of 30 implant sites were prepared in nine fresh bovine bone specimens. The bone density around each preparation was determined by using cone beam computerized tomography (CBCT) and imaging software. Dental implants were then inserted during continuous registration of insertion torque. RFA measurements were performed in perpendicular and parallel to the long axis of the specimens. The bone blocks were embedded in plaster and fixated in a specially designed rig for displacement measurements. A lateral force of 25 N was applied via an abutment perpendicular and parallel to each implant and the displacement measured in µm. In addition, a flex constant (µm N(-1) ) was calculated for each measurement. There was a significant inverse correlation between RFA and lateral implant displacement (µm) measurements and between RFA measurements and the flex constant in both perpendicular and parallel directions in bone (P ≤ 0·001). Moreover, both RFA and displacement measurements correlated with bone density (P ≤ 0·001). It is concluded that RFA measurements reflect the micromobility of dental implants, which in turn is determined by the bone density at the implant site.

Radiological diagnosis of periapical bone tissue lesions in endodontics: a systematic review.

This systematic review evaluates the diagnostic accuracy of radiographic methods employed to indicate presence/absence and changes over time of periapical bone lesions. Also investigated were the leads radiographic images may give about the nature of the process and the condition of the pulp in nonendodontically treated teeth. Electronic literature search included the databases PubMed, Embase and CENTRAL from January 1950 to June 2011. All languages were accepted provided there was an abstract in English. The MeSH terms were 'Cone beam computed tomography (CBCT)', 'Radiography, panoramic', 'Periapical diseases', 'Dental pulp diseases', 'Sensitivity and specificity', 'receiver operating characteristics (ROC) curve', 'Cadaver', 'Endodontics' and 'Radiography dental'. Two reviewers independently assessed abstracts and full text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. Altogether, 181 articles were read in full text. The GRADE approach was used to assess the quality of evidence of each radiographic method based on studies of high or moderate quality. Twenty-six studies fulfilled criteria set for inclusion. None was of high quality; 11 were of moderate quality. There is insufficient evidence that the digital intraoral radiographic technique is diagnostically as accurate as the conventional film technique. The same applies to CBCT. No conclusions can be drawn regarding the accuracy of radiological examination in identifying various forms of periapical bone tissue changes or about the pulpal condition.

Diagnosis of the condition of the dental pulp: a systematic review.

The aim of this systematic review was to appraise the diagnostic accuracy of signs/symptoms and tests used to determine the condition of the pulp in teeth affected by deep caries, trauma or other types of injury. Radiographic methods were not included. The electronic literature search included the databases PubMed, EMBASE, The Cochrane Central Register of Controlled Trials and Cochrane Reviews from January 1950 to June 2011. The complete search strategy is given in an Appendix S1 (available online as Supporting Information). In addition, hand searches were made. Two reviewers independently assessed abstracts and full-text articles. An article was read in full text if at least one of the two reviewers considered an abstract to be potentially relevant. Altogether, 155 articles were read in full text. Of these, 18 studies fulfilled pre-specified inclusion criteria. The quality of included articles was assessed using the QUADAS tool. Based on studies of high or moderate quality, the quality of evidence of each diagnostic method/test was rated in four levels according to GRADE. No study reached high quality; two were of moderate quality. The overall evidence was insufficient to assess the value of toothache or abnormal reaction to heat/cold stimulation for determining the pulp condition. The same applies to methods for establishing pulp status, including electric or thermal pulp testing, or methods for measuring pulpal blood circulation. In general, there are major shortcomings in the design, conduct and reporting of studies in this domain of dental research.

Diagnostic yield of conventional radiographic and cone-beam computed tomographic images in patients with atypical odontalgia.

AIM: To investigate whether the additional diagnostic yield of a cone-beam computed tomography (CBCT) examination over conventional radiographs in patients primarily suspected of having atypical odontalgia (AO) improves differentiation between AO and symptomatic apical periodontitis (SAP) in patients with severe chronic intraoral pain. METHODOLOGY: In this clinical study, 25 patients (mean age 54 ± 11 years, range 34-72) participated; 20 were diagnosed with AO and 5 with SAP. All patients were recruited from the clinics of the Faculty of Odontology, Malmö University. AO inclusion criteria were chronic pain (>6 months) in a region where a tooth had been endodontically or surgically treated, with no pathological cause detectable in clinical or radiologic examinations. SAP inclusion criteria were recurrent pain from a tooth diagnosed with apical periodontitis in clinical and radiographic examinations. Assessments comprised a self-report questionnaire on pain characteristics, a comprehensive clinical examination and a radiographic examination including panoramic and intraoral radiographs and CBCT images. The main outcome measure was periapical bone destruction. RESULTS: Sixty per cent of patients with AO had no periapical bone destructions detectable with any radiographic method. Overall, CBCT rendered 17% more periapical bone destructions than conventional radiography. Average pain intensity in patients with AO was 5.6 (± 1.8) on a 0-10 numerical rating scale, and average pain duration was 4.3 (± 5.2) years. CONCLUSION: Cone-beam computed tomography improves identification of patients without periapical bone destruction, which may facilitate differentiation between AO and SAP.

What you can and cannot see in TMJ imaging--an overview related to the RDC/TMD diagnostic system.

In the current version (I) of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD), imaging of the temporomandibular joint (TMJ) is not required for a diagnosis. Research has shown that radiological findings of the TMJ do not always support the clinical findings of the RDC/TMD diagnosis. But imaging should only be performed when it is known that it could contribute to (i) a proper diagnosis and (ii) treatment with a better prognosis. Several techniques are used to image the TMJ: panoramic radiography, plain radiography, conventional and computed tomography (CT), digital volume tomography or cone-beam computed tomography (CBCT), arthrography and magnetic resonance imaging (MRI). Osseous changes are best visualized in tomography, and the newly developed CBCT is a promising method but must be evaluated in a comparative analysis with other tomographic techniques. And although MRI is the method of choice for imaging the disc, a systematic review found the evidence grade for the diagnostic efficacy of MRI to be insufficient. Today, there is no clear evidence for when TMD patients should be examined with imaging methods. Future research designs should be randomized controlled trials where various radiological examination findings are analysed in relation to therapeutic outcome. In future versions of the RDC/TMD diagnostic system, recommended radiographic techniques must be evaluated and defined, diagnostic criteria well defined and observers calibrated.

Validation of a haemoglobin dilution method for estimation of blood loss.

BACKGROUND AND OBJECTIVES: Analysis of haemoglobin (Hb) dilution after bleeding is a simple, inexpensive and non-invasive method to estimate blood loss. Blood volume is estimated, taking sex, weight and height into account. The Hb concentration before and after blood loss is analysed and, from the difference, the blood loss volume can be calculated assuming a normovolemic subject. Although widely used this method has never been validated. MATERIAL AND METHODS: The Hb concentration of 21 blood donors was analysed before and up to 4 days after a standard blood donation and in another 18 blood donors the Hb concentration was analysed before and on day 4, 6, 8, 11 and 14 after blood donation. The blood volume of each donor was calculated and the donated blood volume was estimated by weighing. We calculated the blood loss by the Hb dilution method and compared the calculated value with the donated blood volume. RESULTS: The mean donated blood volume was 442 +/- 10 ml, whereas the mean calculated blood loss was 152 +/- 214 ml using the Hb concentration of the first day after donation and 301 +/- 145 ml with the Hb concentration of day 6 after blood donation after which no further Hb decrease was observed. The directly measured Hb concentration was always higher than the calculated/expected Hb concentration based on the blood donation volume. CONCLUSIONS: The Hb dilution method underestimates the true blood loss by more than 30% after a moderate blood loss of approximately 10% of the total blood volume.

Stress-induced single-polarization single-transverse mode photonic crystal fiber with low nonlinearity.

We report on the design of a single-polarization single-transverse mode large mode area photonic crystal fiber. By including index-matched stress applying elements in the photonic cladding an ultra-broadband single polarization window is obtained while a large mode field area of ~700 microm(2) is maintained. Based on that design, an Yb-doped double-clad photonic crystal fiber is realized that combines low nonlinearity and single polarization properties. A first result of the high power operation using this fiber is demonstrated.

High-power rod-type photonic crystal fiber laser.

We report on a novel ytterbium-doped fiber design that combines the advantages of rod and fiber gain media. The fiber design has outer dimensions of a rod laser, meaning a diameter in the range of a few millimeters and a length of just a few tens of centimeters, and includes two important waveguide structures, one for pump radiation and one for laser radiation. We obtained 120-W output power in single-mode beam quality from a 48-cm-long fiber cane that corresponds to an extracted power of 250 W/m. The fiber has significantly reduced nonlinearity, which therefore allows for scalability in the performance of a high-peak-power fiber laser and amplifier system.

TACC3 deregulates the DNA damage response and confers sensitivity to radiation and PARP inhibition.

Deregulation of the transforming acidic coiled-coil protein 3 (TACC3), an important factor in the centrosome-microtubule system, has been linked to a variety of human cancer types. We have recently reported on the oncogenic potential of TACC3; however, the molecular mechanisms by which TACC3 mediates oncogenic function remain to be elucidated. In this study, we show that high levels of TACC3 lead to the accumulation of DNA double-strand breaks (DSBs) and disrupt the normal cellular response to DNA damage, at least in part, by negatively regulating the expression of ataxia telangiectasia mutated (ATM) and the subsequent DNA damage response (DDR) signaling cascade. Cells expressing high levels of TACC3 display defective checkpoints and DSB-mediated homologous recombination (HR) and non-homologous end joining (NHEJ) repair systems, leading to genomic instability. Importantly, high levels of TACC3 confer cellular sensitization to radiation and poly(ADP-ribose) polymerase (PARP) inhibition. Overall, our findings provide critical information regarding the mechanisms by which TACC3 contributes to genomic instability, potentially leading to cancer development, and suggest a novel prognostic, diagnostic and therapeutic strategy for the treatment of cancer types expressing high levels of TACC3.

Intranasal administration of human growth hormone (hGH) in combination with a membrane permeation enhancer in patients with GH deficiency: a pharmacokinetic study.

Recombinant human GH (hGH) combined with a permeation enhancer for the nasal mucosa, sodium tauro-24,25-dihydrofusidate (STDHF), was administered intranasally (in) in six patients with classical GH deficiency. Three different doses were tested (0.2, 0.4, and 0.8 IU/kg BW). The concentration of STDHF was 1% in all doses. As a comparison, all patients received a sc injection of hGH (0.1 IU/kg BW). Blood samples were obtained at frequent intervals for up to 8 h (in doses) or 24 h (sc dose) and analyzed for the plasma concentration of hGH. All three i.n. doses gave a rapid increase in hGH with peak maxima (Cmax) at 20-30 min, and a decline to baseline within 2-3 h. In contrast, the sc dose resulted in a Cmax 2-3 h after the injection, followed by a plateau phase for 2-3 h. The baseline was reached 12-14 h after administration. The uptake [area under the curve (AUC)] was considerably lower for all three in doses, i.e. 1.6-3% of the AUC obtained with the sc dose. However, the Cmax varied between 5.7 +/- 1.4% (0.8 IU/kg BW) and 15.8 +/- 2.1% (0.4 IU/kg BW) of the maximal peak with the sc dose. Of the in doses, 0.4 IU/kg BW resulted in the highest AUC and Cmax. A self-rating protocol was also used to estimate nasal sensations for up to 2 h after dosing. All sensations (itching, burning, sneezing, and running of the nose) were transient and tolerable. This study demonstrates that hGH can be administered intranasally in combination with STDHF. The in dosing results in a plasma peak of hGH very similar to the physiological endogenous peak. No side-effects were noted, other than a transient nasal irritation. Therefore, the nasal route for hGH administration offers a more physiological and more convenient alternative to injections for the treatment of GH deficiency.

Nitric oxide metabolites in CSF of patients with MS are related to clinical disease course.

In this study, we have analyzed the stable metabolites of nitric oxide (NO), nitrite and nitrate, in the CSF of patients with MS, lymphocytic meningitis, and in healthy control subjects. Patients with MS with an active disease course exhibited increased CSF nitrite levels compared with patients with stable MS and healthy control subjects, whereas CSF nitrate levels did not differ between these groups. High CSF levels of both metabolites were seen in patients with meningitis. These data indicate that CSF nitrite levels may reflect clinical disease activity in MS.

Dependence of the metabolism of nitric oxide (NO) in healthy human whole blood on the oxygenation of its red cell haemoglobin.

Plasma or whole venous or arterialized blood from healthy human donors was incubated with NO (50-300 microM), and the resulting formation of methaemoglobin (MetHb), nitrosyl haemoglobin (HbNO), and plasma nitrite and nitrate were measured. In plasma, NO was converted to nitrite and nitrate in a ratio of 5:1. In arterial blood (O2 sat. 94-99%) NO was almost quantitatively converted to nitrate and MetHb. No nitrite was detected and HbNO formation was low. In venous blood (O2 sat. 36-85%) more HbNO and less nitrate was formed, in comparison to arterialized blood. We propose that NO liberated from endothelium of conductance and resistance vessels is taken up by red blood cells and inactivated by HbO2 via stoichiometric conversion to MetHb and nitrate.

Nitric oxide-donating properties of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives.

1. The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2. GEA 3162, GEA 3175, SIN-1 and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 microM, respectively). All four compounds induced a dose-dependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 microM) and inhibited 38-97% by oxyhaemoglobin (10-45 microM). 3. All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-1 and SNAP (100 microM) produced 50-70 microM NO2- + NO3- as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4. The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-1 and SNAP release nitric oxide.

Isolation and partial characterization of immunoglobulin from cod (Gadus morhua L.).

Serum immunoglobulins (CS-Ig) from cod (Gadus morhua L.) were prepared by precipitation with ammonium sulphate and molecular sieving. The molecular weight estimated from molecular sieving and electrophoresis was 851 kD for the whole molecule and 81 and 27.5 kD for the two subunits. This suggests a tetrameric structure of the molecule. The isoelectric point of CS-Ig was determined to approximately pH 5.0. The amino acid composition and absorbancy at 280 nm are very similar to published data of IgM from other fish species as well as from several mammals. CS-Ig has a natural binding capacity to a number of antigens used for immunization. Assays of antibody activity of fractionated cod serum indicates that CS-Ig does not exist as a monomeric molecule. As the characteristics of CS-Ig are very similar to those found in other fish species, we believe that CS-Ig is an IgM-like molecule.

Multi-mode photonic crystal fibers for VCSEL based data transmission.

Quasi error-free 10Gbit/s data transmission is demonstrated over a novel type of 50 microm core diameter photonic crystal fi ber with as much as 100m length. Combined with 850 nm VCSEL sources, this fi ber is an attractive alternative to graded-index multi-mode fi bers for datacom applications. A comparison to numerical simulations suggests that the high bit-rate may be partly explained by inter-modal diffusion.