Flexible versus Fixed Spatial Self-Ordered Response Sequencing: Effects of Inactivation and Neurochemical Modulation of Ventrolateral Prefrontal Cortex.

Previously, studies using human neuroimaging and excitotoxic lesions in non-human primate have demonstrated an important role of ventrolateral prefrontal cortex (vlPFC) in higher order cognitive functions such as cognitive flexibility and the planning of behavioral sequences. In the present experiments, we tested effects on performance of temporary inactivation (using GABA receptor agonists) and dopamine (DA) D2 and 5-HT2A-receptor (R) blockade of vlPFC via local intracerebral infusions in the marmoset. We trained common marmosets to perform spatial self-ordered sequencing tasks in which one cohort of animals performed two and three response sequences on a continuously varying spatial array of response options on a touch-sensitive screen. Inactivation of vlPFC produced a marked disruption of accuracy of sequencing which also exhibited significant error perseveration. There were somewhat contrasting effects of D2 and 5-HT2A-R blockade, with the former producing error perseveration on incorrect trials, though not significantly impairing accuracy overall, and the latter significantly impairing accuracy but not error perseveration. A second cohort of marmosets were directly compared on performance of fixed versus variable spatial arrays. Inactivation of vlPFC again impaired self-ordered sequencing, but only with varying, and not fixed spatial arrays, the latter leading to the consistent use of fewer, preferred sequences. These findings add to evidence that vlPFC is implicated in goal-directed behavior that requires higher-order response heuristics that can be applied flexibly over different (variable), as compared with fixed stimulus exemplars. They also show that dopaminergic and serotonergic chemomodulation has distinctive effects on such performance.SIGNIFICANCE STATEMENT This investigation employing local intracerebral infusions to inactivate the lateral prefrontal cortex (PFC) of the New World marmoset reveals the important role of this region in self-ordered response sequencing in variable but not fixed spatial arrays. These novel findings emphasize the higher order functions of this region, contributing to cognitive flexibility and planning of goal directed behavior. The investigation also reports for the first time somewhat contrasting neuromodulatory deficits produced by infusions of dopamine (DA) D2 and 5-HT2A receptor (R) antagonists into the same region, of possible significance for understanding cognitive deficits produced by anti-psychotic drugs.

Caries risk assessment. A systematic review.

OBJECTIVE: To assess the ability of multivariate models and single factors to correctly identify future caries development in pre-school children and schoolchildren/adolescents. STUDY DESIGN: A systematic literature search for relevant papers was conducted with pre-determined inclusion criteria. Abstracts and full-text articles were assessed independently by two reviewers. The quality of studies was graded according to the QUADAS tool. The quality of evidence of models and single predictors was assessed using the GRADE approach. RESULTS: Ninety original articles fulfilled the inclusion criteria. Seven studies had high quality, 35 moderate and the rest poor quality. The accuracy of multivariate models was higher for pre-school children than for schoolchildren/adolescents. However, the models had seldom been validated in independent populations, making their accuracy uncertain. Of the single predictors, baseline caries experience had moderate/good accuracy in pre-school children and limited accuracy in schoolchildren/adolescents. The period of highest risk for caries incidence in permanent teeth was the first few years after tooth eruption. In general, the quality of evidence was limited. CONCLUSIONS: Multivariate models and baseline caries prevalence performed better in pre-school children than in schoolchildren/adolescents. Baseline caries prevalence was the most accurate single predictor in all age groups. The heterogeneity of populations, models, outcome criteria, measures and reporting hampered the synthesis of results. There is a great need to standardize study design, outcome measures and reporting of data in studies on caries risk assessment. The accuracy of prediction models should be validated in at least one independent population.

The Anticipated Positive Psychosocial Impact of Present Web-Based E-Health Services and Future Mobile Health Applications: An Investigation among Older Swedes.

This study investigates the anticipated psychosocial impact of present web-based e-health services and future mobile health applications among older Swedes. Random sample's of Swedish citizens aged 55 years old and older were given a survey containing two different e-health scenarios which respondents rated according to their anticipated psychosocial impact by means of the PIADS instrument. Results consistently demonstrated the positive anticipation of psychosocial impacts for both scenarios. The future mobile health applications scored more positively than the present web-based e-health services. An increase in age correlated positively to lower impact scores. These findings indicate that from a psychosocial perspective, web-based e-health services and mobile health applications are likely to positively impact quality of life. This knowledge can be helpful when tailoring and implementing e-health services that are directed to older people.

Regulatory T cell phenotype and function 4 years after GAD-alum treatment in children with type 1 diabetes.

Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. We have carried out a 4-year follow-up study of 59 of the original 70 patients to investigate long-term effects on the frequency and function of regulatory T cells after GAD-alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD65 for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD-alum- and placebo-treated individuals. Regulatory T cell frequency did not correlate with C-peptide secretion throughout the study. In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment.

Radiobiological evaluation of breast cancer radiotherapy accounting for the effects of patient positioning and breathing in dose delivery. A meta analysis.

In breast cancer radiotherapy, significant discrepancies in dose delivery can contribute to underdosage of the tumor or overdosage of normal tissue, which is potentially related to a reduction of local tumor control and an increase of side effects. To study the impact of these factors in breast cancer radiotherapy, a meta analysis of the clinical data reported by Mavroidis et al. (2002) in Acta Oncol (41:471-85), showing the patient setup and breathing uncertainties characterizing three different irradiation techniques, were employed. The uncertainties in dose delivery are simulated based on fifteen breast cancer patients (5 mastectomized, 5 resected with negative node involvement (R-) and 5 resected with positive node involvement (R1)), who were treated by three different irradiation techniques, respectively. The positioning and breathing effects were taken into consideration in the determination of the real dose distributions delivered to the CTV and lung in each patient. The combined frequency distributions of the positioning and breathing distributions were obtained by convolution. For each patient the effectiveness of the dose distribution applied is calculated by the Poisson and relative seriality models and a set of parameters that describe the dose-response relations of the target and lung. The three representative radiation techniques are compared based on radiobiological measures by using the complication-free tumor control probability, P(+) and the biologically effective uniform dose, (BEUD)concepts. For the Mastectomy case, the average P(+) values of the planned and delivered dose distributions are 93.8% for a (BEUD)(CTV) of 51.8 Gy and 85.0% for a (BEUD)(CTV) of 50.3 Gy, respectively. The respective total control probabilities, P(B) values are 94.8% and 92.5%, whereas the corresponding total complication probabilities, P(1) values are 0.9% and 7.4%. For the R- case, the average P(+) values are 89.4% for a (BEUD)(CTV) of 48.9 Gy and 88.6% for a (BEUD)(CTV) of 49.2 Gy and 85.5% for a (BEUD)(CTV) of 49.1 Gy, respectively. The respective PB values are 90.2% and 90.1%, whereas the corresponding P(+) values are 4.1% and 4.6%. The combined effects of positioning uncertainties and breathing can introduce a significant deviation between the planned and delivered dose distributions in lung in breast cancer radiotherapy. The positioning and breathing uncertainties do not affect much the dose distribution to the CTV. The simulated delivered dose distributions show larger lung complication probabilities than the treatment plans. This means that in clinical practice the true expected complications are underestimated. Radiation pneumonitis of Grade 1-2 is more frequent and any radiotherapy optimization should use this as a more clinically relevant endpoint.

Bell's palsy - the effect of prednisolone and/or valaciclovir versus placebo in relation to baseline severity in a randomised controlled trial.

OBJECTIVES: To evaluate the treatment effect of prednisolone and/or valaciclovir in Bell's palsy patients with different baseline severity of palsy. DESIGN: Patient data were collected from the Scandinavian Bell's Palsy Study, a prospective, randomised, double-blind, placebo-controlled, multi-centre trial. SETTING: Sixteen otorhinolaryngological centres in Sweden and one in Finland. PARTICIPANTS: Altogether, 829 patients aged 18-75 years were treated within 72 h of palsy onset. Patients were randomly assigned to treatment with prednisolone plus placebo (n = 210), valaciclovir plus placebo (n = 207), prednisolone plus valaciclovir (n = 206), placebo plus placebo (n = 206). Follow-up was 12 months. MAIN OUTCOME MEASURES: Facial function was assessed using the Sunnybrook grading scale at baseline and at 12 months. Complete recovery was defined as Sunnybrook score = 100. RESULTS: All patients, regardless of baseline severity, showed significantly higher complete recovery rates if treated with prednisolone compared with no prednisolone. In patients with severe palsy, recovery at 12 months was 51% with prednisolone treatment versus 31% without prednisolone (P = 0.02). Corresponding results were 68%versus 51% (P = 0.004) for moderate, and 83%versus 73% (P = 0.02) for mild palsy. In patient groups with moderate and mild palsy at baseline, significantly fewer prednisolone-treated patients had synkinesis at 12 months (P = 0.04 and P < 0.0001, respectively). For patients with severe palsy at baseline, prednisolone versus no prednisolone made no significant difference regarding synkinesis at 12 months. Valaciclovir did not add any significant effect to prednisolone regarding recovery rate or synkinesis at 12 months. CONCLUSION: Prednisolone treatment resulted in higher complete recovery rates, regardless of severity at baseline. Prednisolone treatment should be considered in all patients irrespective of degree of palsy.

Decreased GAD(65)-specific Th1/Tc1 phenotype in children with Type 1 diabetes treated with GAD-alum.

AIM: The balance between T helper cell subsets is an important regulator of the immune system and is often examined after immune therapies. We aimed to study the immunomodulatory effect of glutamic acid decarboxylase (GAD) 65 formulated with aluminium hydroxide (GAD-alum) in children with Type 1 diabetes, focusing on chemokines and their receptors. METHODS: Blood samples were collected from 70 children with Type 1 diabetes included in a phase II clinical trial with GAD-alum. Expression of CC chemokine receptor 5 (CCR5) and CCR4 was analysed on CD4+ and CD8+ lymphocytes after in vitro stimulation with GAD(65) using flow cytometry, and secretion of the chemokines CCL2, CCL3 and CCL4 was detected in peripheral blood mononuclear cell supernatants with Luminex. RESULTS: Expression of Th1-associated CCR5 was down-regulated following antigen challenge, together with an increased CCR4/CCR5 ratio and CCL2 secretion in GAD-alum-treated patients, but not in the placebo group. CONCLUSION: Our results suggest that GAD-alum treatment has induced a favourable immune modulation associated with decreased Th1/Tc1 phenotypes upon antigen re-challenge, which may be of importance for regulating GAD(65) immunity.

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.

A cost-minimization analysis of root canal treatment before and after education in nickel-titanium rotary technique in general practice.

AIM: To compare root canal treatments performed before and after education in a nickel-titanium rotary technique (NiTiR) with respect to costs for instrumentation and number of instrumentation sessions in a County Public Dental Service in Sweden. METHODOLOGY: Following education, 77% of the general dental practitioners adopted completely the NiTiR. The randomly selected sample comprised 850 root canal treatments: 425 performed after the education, mainly using the NiTiR-technique (group A) and 425 performed before, using mainly stainless steel hand instrumentation (SSI) (group B). The number of instrumentation sessions in root canal treatments in group A and B was calculated. A CMA was undertaken on the assumption that treatment outcome was identical in group A and B. Direct costs associated with SSI and NiTiR were estimated and compared. Investment costs required for implementation of NiTiR were calculated, but not included in the CMA. RESULTS: Instrumentation sessions were counted in 418 (98%) root canal treatments performed in group A and 419 (99%) in group B. The number of instrumentation sessions in group A was significantly lower; 2.38, compared with 2.82 in group B (P < 0.001). Thus, on average, for every second root canal treatment performed after the education, one instrumentation session was saved. Root canal treatments in teeth with one canal, and three or more canals, were completed in significantly fewer instrumentation sessions after the education (P < 0.001). Direct costs of instrumentation sessions were SEK 2587 (USD 411) for group A and SEK 2851 (USD 453) for group B, for teeth with one canal, and SEK 2946 (USD 468) for group A and SEK 3510 (USD 558) for group B, for teeth with three or more canals (year 2011). Root canal treatments of teeth with two canals showed no significant difference with respect to number of instrumentation sessions and costs. CONCLUSIONS: Significantly fewer instrumentation sessions were required in group A, and root canal instrumentation therefore costs less than in group B. On the assumption that treatment outcome is identical in group A and B, root canal instrumentation performed after the education was more cost-effective.

Extended evaluation of the safety and efficacy of GAD treatment of children and adolescents with recent-onset type 1 diabetes: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to investigate the safety and efficacy of alum formulated glutamic acid decarboxylase GAD(65) (GAD-alum) treatment of children and adolescents with type 1 diabetes after 4 years of follow-up. METHODS: Seventy children and adolescents aged 10-18 years with recent onset type 1 diabetes participated in a phase II, double-blind, randomised placebo-controlled clinical trial. Patients identified as possible participants attended one of eight clinics in Sweden to receive information about the study and for an eligibility check, including a medical history. Participants were randomised to one of the two treatment groups and received either a subcutaneous injection of 20 µg of GAD-alum or placebo at baseline and 1 month later. The study was blinded to participants and investigators until month 30. The study was unblinded at 15 months to the sponsor and statistician in order to evaluate the data. At follow-up after 30 months there was a significant preservation of residual insulin secretion, as measured by C-peptide, in the group receiving GAD-alum compared with placebo. This was particularly evident in patients with <6 months disease duration at baseline. There were no treatment-related serious adverse events. We have now followed these patients for 4 years. Overall, 59 patients, 29 who had been treated with GAD-alum and 30 who had received placebo, gave their informed consent. RESULTS: One patient in each treatment group experienced an episode of keto-acidosis between months 30 and 48. There were no treatment-related adverse events. The primary efficacy endpoint was the change in fasting C-peptide concentration from baseline to 15 months after the prime injection for all participants per protocol set. In the GAD-alum group fasting C-peptide was 0.332 ± 0.032 nmol/l at day 1 and 0.215 ± 0.031 nmol/l at month 15. The corresponding figures for the placebo group were 0.354 ± 0.039 and 0.184 ± 0.033 nmol/l, respectively. The decline in fasting C-peptide levels between day 1 and month 1, was smaller in the GAD-alum group than the placebo group. The difference between the treatment groups was not statistically significant. In those patients who were treated within 6 months of diabetes diagnosis, fasting C-peptide had decreased significantly less in the GAD-alum group than in the placebo-treated group after 4 years. CONCLUSION/INTERPRETATION: Four years after treatment with GAD-alum, children and adolescents with recent-onset type 1 diabetes continue to show no adverse events and possibly to show clinically relevant preservation of C-peptide. TRIAL REGISTRATION: ClinicalTrials.gov NCT00435981 FUNDING: The study was funded by The Swedish Research Council K2008-55X-20652-01-3, Barndiabetesfonden (The Swedish Child Diabetes Foundation), the Research Council of Southeast Sweden, and an unrestricted grant from Diamyd Medical AB.

Management of TMD: evidence from systematic reviews and meta-analyses.

This systematic review (SR) synthesises recent evidence and assesses the methodological quality of published SRs in the management of temporomandibular disorders (TMD). A systematic literature search was conducted in the PubMed, Cochrane Library, and Bandolier databases for 1987 to September 2009. Two investigators evaluated the methodological quality of each identified SR using two measurement tools: the assessment of multiple systematic reviews (AMSTAR) and level of research design scoring. Thirty-eight SRs met inclusion criteria and 30 were analysed: 23 qualitative SRs and seven meta-analyses. Ten SRs were related to occlusal appliances, occlusal adjustment or bruxism; eight to physical therapy; seven to pharmacologic treatment; four to TMJ and maxillofacial surgery; and six to behavioural therapy and multimodal treatment. The median AMSTAR score was 6 (range 2-11). Eighteen of the SRs were based on randomised clinical trials (RCTs), three were based on case-control studies, and nine were a mix of RCTs and case series. Most SRs had pain and clinical measures as primary outcome variables, while few SRs reported psychological status, daily activities, or quality of life. There is some evidence that the following can be effective in alleviating TMD pain: occlusal appliances, acupuncture, behavioural therapy, jaw exercises, postural training, and some pharmacological treatments. Evidence for the effect of electrophysical modalities and surgery is insufficient, and occlusal adjustment seems to have no effect. One limitation of most of the reviewed SRs was that the considerable variation in methodology between the primary studies made definitive conclusions impossible.

Effect of educational intervention on adoption of new endodontic technology by general dental practitioners: a questionnaire survey.

OBJECTIVES: To survey the clinical endodontic protocols of general dental practitioners (GDPs) in public dental clinics and to assess the effect of an educational intervention on the adoption of a nickel-titanium (Ni-Ti) rotary system. METHODS: General dental practitioners in a Swedish Intervention County (IC), underwent an educational programme in endodontics. A follow-up questionnaire was posted to 98 GDPs in the IC and to 97 GDPs in a Control County (CC), where no specific training had been provided. The questionnaire concerned demographics, clinical endodontic protocols and instrumentation techniques. RESULTS: The response rate to the questionnaire was 87%. More than 90% of all GDPs reported they always or generally used rubber dam, determined working length, used the canal irrigant 0.5% buffered NaOCl and calcium hydroxide as an interappointment dressing. Two of three GDPs reported, they generally or always informed the patient of the prognosis. Every second GDP reported routines for postoperative recall and follow-up. The Ni-Ti rotary technique was reported to be completely adopted by 77% of the GDPs in the IC, significantly higher than in the CC (6%), P < 0.001. In the IC 79% of the GDPs reported they completed instrumentation in one treatment session, compared with only 32% in the CC, P < 0.001. The 'single-cone' mode of canal filling was reported to be significantly more frequent amongst GDPs in the IC, P < 0.001. CONCLUSIONS: General dental practitioners in both counties reported using contemporary clinical endodontic protocols. GDPs who had undergone an educational programme in Ni-Ti rotary instrumentation reported they had successfully integrated the technique into daily clinical practice.

Impaired CD4 and CD8 T cell phenotype and reduced chemokine secretion in recent-onset type 1 diabetic children.

Although the role of the T cell-mediated autoimmune reaction in type 1 diabetes (T1D) is conclusive, studies including data from human circulating CD4(+) and CD8(+) lymphocytes subsets during the disease onset and posterior development are scarce. Further, chemokines and chemokine receptors are key players in the migration of pathogenic T cells into the islets of non-obese diabetic mice developing T1D, but few studies have investigated these markers in human T1D patients. We studied the expression of T helper 1 (Th1)- and Th2-associated chemokine receptors, and the two isoforms of CD45 leucocyte antigen on CD4(+) and CD8(+) lymphocytes from T1D and healthy children, as well as the secretion of chemokines in cell supernatants in peripheral blood mononuclear cells. Our results showed increased expression of CCR7 and CD45RA and reduced CD45RO on CD8(+) cells among recent-onset T1D patients. The percentages of CD4(+) cells expressing CXC chemokine receptor 3 (CXCR3), CXCR6 and CCR5, and the secretion of interferon-gamma-induced protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein (MIP)-1alpha and MIP-1beta was lower among diabetics. Low expression of Th1-associated receptors and secretion of chemokines, together with an increased amount of CD8(+) cells expressing CD45RA and CCR7 in T1D patients therefore might represent suboptimal Th function in T1D, leading to impaired T cytotoxic responses or alternatively reflect a selective recruitment of Th1 cells into the pancreas.

Environmental tobacco smoke exposure in public places of European cities.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has important public health implications. The results of the first European multi-centre study that measured ETS exposure in a range of public places (transport, educational settings, and leisure facilities such as bars and restaurants) are presented. METHOD: Nicotine vapour phase was measured using ETS passive samplers containing a filter treated with sodium bisulfate. RESULTS: Bars and discos are the places with the highest concentrations of nicotine from ETS, median ranging from 19 to 122 microg/m(3). Restaurants had the next highest values. Concentrations of nicotine generally range from 0.1-5 microg/m(3) in airports, and from 0.5-10 microg/m(3) in train stations. Nicotine was also found in schools and universities, yet schools tended to have the lowest concentrations compared to all the other public places sampled. In hospitals levels were generally below 5 microg/m(3). CONCLUSIONS: Although there is some variability between cities, this study shows that tobacco smoke is present in most of the studied public places. The study also showed that in areas where smoking is prohibited, concentrations of nicotine are lower than in areas where smoking is allowed but they are not zero. The results of this study indicate that policies should be implemented that would effectively reduce levels of tobacco smoke in public areas.

Exposure assessment to alpha- and beta-pinene, delta(3)-carene and wood dust in industrial production of wood pellets.

The main aim of the study was to measure the exposure to monoterpenes (alpha- and beta-pinene and Delta(3)-carene) and wood dust during industrial production of wood pellets and briquettes. Additional aims were to compare the results from wood dust sampled on a filter with real time measurements using a direct reading instrument and to identify peak exposures to dust. Twenty-four men working at six companies involved in industrial production of wood pellets and briquettes participated in the study. Monoterpenes were measured by diffusive sampling and wood dust was measured as total dust. A data logger (DataRAM) was used for continuous monitoring of dust concentration for 18 of the participants. The sampling time was approximately 8 h. The personal exposure to monoterpenes ranged from 0.64 to 28 mg/m(3) and a statistically significant (Kruskal-Wallis test, P = 0.0002) difference in levels of monoterpenes for workers at different companies was seen. In the companies the personal exposure to wood dust varied between 0.16 and 19 mg/m(3) and for 10 participants the levels exceeded the present Swedish occupational exposure limit (OEL) of 2 mg/m(3). The levels of wood dust during the morning shift were significantly (Mann-Whitney test, P = 0.04) higher compared with the afternoon shift. Continuous registration of dust concentration showed peak values for several working operations, especially cleaning of truck engines with compressed air. For 24 workers in six companies involved in industrial production of wood pellets the personal exposure to monoterpenes was low and to wood dust high compared with the present Swedish OEL and previous studies in Swedish wood industries. Since the DataRAM can identify critical working tasks with high wood dust exposure a reduction in exposure levels could probably be achieved by changes in working routines and by the use of protective equipment.

The basic reality of mind and spongiform diseases.

A change in handedness (chirality) in some amino acids appears to be the basic physical change in degradation-resistant proteins (prions) found in conditions such as Creutzfeldt-Jacob disease (CJD), Alzheimer's disease (AD), bovine spongiform encephalopathy (BSE) and ovine scrapie. The affected structures are primarily innervated by cholinergic nerves. Much evidence suggests that these so-called prions (here named chirons) are harmless, non-infectious products. The importance of the cholinergic system allows a new simplified interpretation of these conditions. The main steps are the acetylcholine-cholinesterase splitting of body water with release of free protons in solution, followed by electron dissipation, dioxygen activation and Ca-fluxes. Abiotic physics conserves parity and symmetry by equal amounts of L- and D-forms of molecules. In contrast, the asymmetric pattern of life must be homochiral. Such biomolecules dissolve in water and are thus able to interact in cholinergic hydrodynamics. It is supposed that the instability of the composite weak force by beta-decay causes changes in chirality. These extremely rare events are not frequent enough to explain disease pathology. Experimental, accidental, surgical and abusive inoculations will propagate chirons according to the physical law of self-replication, which also occurs in test tubes without added biological products. Chirons will not be degraded into amino acids in the alimentary canal and will, because they are indigestible, leave the body with the faeces. Chirons are inert also to the immune system and will be engulfed without reaction by phagocytosing cells. They are then stored away in tissues, where they do no harm (if not detected and suspected to be deleterious, thereby causing pathogenic anxiety). The cholinergic system reacts to all kinds of integrity threats and it is this reaction which I propose causes the so-called prion diseases. This pathology seems generally valid, and is here exemplified in AD, CJD, and Kuru disease. It is the cholinergic reaction and not the agent per se that is pathogenic. This is also true of viral infections where the interaction between viral infection and response may explain the enigmatic epidemiology of many neurodegenerative diseases. Intensity and duration of challenges will determine pathophysiology. The new variant of CJD, vCJD, is assumed to result from mutation of a slow virus agent into a more intense variant, which will give disease in younger patients. The pathology is primary protonic, with overactivity in most sub-systems of either enhancing or inhibiting character, but also functional failure or cell death by membrane damage and acidification, for instance in the CNS. The practical results of this proposal will be alleviation of the current BSE crisis. The important main aspects are: chirons are not infectious proteins but inert physical by-products; they are indigestible and not immunogenic, so beef is safe; properly processed and handled meat and bone-meal are not likely to transmit neurodegenerative diseases; chirons cannot even serve as markers in neurologic diseases.

A comparison of discectomy and arthroscopic lysis and lavage for the treatment of chronic closed lock of the temporomandibular joint: a randomized outcome study.

PURPOSE: The study compared the efficacy of discectomy or arthroscopic lysis and lavage in patients with chronic closed lock of the temporomandibular joint (TMJ) in a prospective, randomized clinical trial. PATIENTS AND METHODS: Twenty-two patients with a clinical diagnosis of chronic closed lock were prospectively randomized to either discectomy or arthroscopic lysis and lavage. The individual outcome in each patient was evaluated with a visual analog scale for pain and a questionnaire concerning mandibular functional impairment. The clinical evaluation included measurement of maximum interincisal opening and protrusion, recording of clicking and crepitation, and palpation for tenderness of the TMJ and jaw muscles. Recordings were made before the operation (baseline) and at the 1-year follow-up. RESULTS: Twenty patients completed the study. Discectomy and arthroscopic lysis and lavage significantly reduced pain and improved mandibular function. Discectomy reduced pain somewhat more effectively than arthroscopic lysis and lavage. The clinical recordings at the 1-year follow-up indicated similarly good outcomes after both procedures. CONCLUSION: Both discectomy and arthroscopic lysis and lavage are effective surgical methods for treatment of chronic closed lock of the TMJ. Considering that arthroscopic lysis and lavage is a minimally invasive outpatient procedure, it should be used as the first choice in surgical treatment of this condition.

The major fluvoxamine metabolite in urine is formed by CYP2D6.

OBJECTIVE: Previous studies have shown that fluvoxamine is metabolized by CYP1A2 and CYP2D6, but there is no information on the impact the various CYP enzymes have on the different metabolic pathways of fluvoxamine biotransformation. The present study was designed to investigate this issue. METHODS: The major fluvoxamine metabolite, the 5-demethoxylated carboxylic acid metabolite, was analyzed in urine from 50 healthy volunteers after intake of a single oral dose of 50 mg fluvoxamine, and the formation clearance for the metabolite (CLm) was calculated. Of the subjects, 28 were non-smoking CYP2D6 and CYP2C19 extensive metabolizers (EMs), 12 were smokers and were thus considered to have an induced CYP1A2 activity, 5 were CYP2D6 poor metabolizers (PMs), and 5 were CYP2C19 PMs. In 11 of the non-smoking EMs, 200 mg caffeine was given at another occasion in order to calculate oral caffeine clearance as a measure of CYP1A2 activity. In addition, CLm was calculated in ten other subjects given increasing doses of fluvoxamine for 4 weeks. RESULTS: Oral clearance of fluvoxamine was significantly higher in smokers, and significantly lower in CYP2D6 PMs than in non-smoking EMs. CLm was 78% lower in CYP2D6 PMs than in the EMs. Smoking and being a CYP2C19 PM did not influence CLm. There was no significant correlation between oral caffeine clearance and CLm. CLm decreased with increasing fluvoxamine dosage, but the decrease in oral clearance was even higher. CONCLUSION: These results indicate that CYP2D6 catalyzes the major metabolic pathway of fluvoxamine, whereas CYP1A2 seems to catalyze other less important pathways. Both the CYP2D6 and the CYP1A2 pathways seem to be saturated in parallel with increasing fluvoxamine dosage.