Multicenter evaluation of a commercial cytomegalovirus quantitative standard: effects of commutability on interlaboratory concordance.

Commutability of quantitative reference materials has proven important for reliable and accurate results in clinical chemistry. As international reference standards and commercially produced calibration material have become available to address the variability of viral load assays, the degree to which such materials are commutable and the effect of commutability on assay concordance have been questioned. To investigate this, 60 archived clinical plasma samples, which previously tested positive for cytomegalovirus (CMV), were retested by five different laboratories, each using a different quantitative CMV PCR assay. Results from each laboratory were calibrated both with lab-specific quantitative CMV standards ("lab standards") and with common, commercially available standards ("CMV panel"). Pairwise analyses among laboratories were performed using mean results from each clinical sample, calibrated first with lab standards and then with the CMV panel. Commutability of the CMV panel was determined based on difference plots for each laboratory pair showing plotted values of standards that were within the 95% prediction intervals for the clinical specimens. Commutability was demonstrated for 6 of 10 laboratory pairs using the CMV panel. In half of these pairs, use of the CMV panel improved quantitative agreement compared to use of lab standards. Two of four laboratory pairs for which the CMV panel was noncommutable showed reduced quantitative agreement when that panel was used as a common calibrator. Commutability of calibration material varies across different quantitative PCR methods. Use of a common, commutable quantitative standard can improve agreement across different assays; use of a noncommutable calibrator can reduce agreement among laboratories.

Diagnostic value of 2D and 3D imaging in odontogenic maxillary sinusitis: a review of literature.

This review aims to explore whether 3D imaging offers an added value in diagnosis of odontogenic sinusitis. Odontogenic maxillary sinusitis accounts for approximately 10-12% of maxillary sinusitis cases. Proper diagnosis of odontogenic sinusitis is based on a thorough dental and medical examination and crucial to ensure therapeutic efficacy. To establish the odontogenic cause of maxillary sinusitis, 2D and 3D imaging modalities may be considered, each presenting distinct advantages and drawbacks. The available research indicates that 2D imaging modalities may often mask the origin of odontogenic maxillary sinusitis. This limitation is particularly evident in the maxillary molar region, stressing the need for 3D cross-sectional imaging. The advent of low-dose cone beam computed tomography in dentistry may be particularly useful when odontogenic maxillary sinusitis is not responsive to therapy. Yet, it seems that more research is needed to validate its use in odontogenic maxillary sinusitis.

The diagnostic efficacy of cone beam CT for impacted teeth and associated features: a systematic review.

This review evaluates the evidence for the diagnostic efficacy of cone beam computed tomography (CBCT) for impacted teeth and associated features. PubMed, Embase and the Cochrane Library were searched using specific indexing terms and reference lists were hand searched. Two reviewers selected relevant publications on the basis of pre-determined inclusion criteria. Original studies were assessed using a modification of the quality assessment of diagnostic accuracy studies (QUADAS) tool. The literature search yielded 96 titles, of which 7 were included in the review. There was only limited evidence for diagnostic efficacy expressed as sensitivity, specificity and predictive values. Only two studies compared CBCT and panoramic radiographs with a valid reference method and presented the results in terms of percentage of correct diagnoses. This review reveals a need for studies that meet methodological standards for diagnostic efficacy of CBCT in the diagnosis of impacted teeth.

Accuracy and surgical feasibility of a CBCT-based stereolithographic surgical guide aiding autotransplantation of teeth: in vitro validation.

The aims of this study were to determine the accuracy of a 3D computer model and stereolithographic (STL) replica when compared to the real tooth and to develop a cone beam computed tomography (CBCT)-based planning technique including surgical guide fabrication. A STL surgical guide and a tooth replica were fabricated using SimPlant Pro 12.1. To validate this process, tooth segmentation and replica design were prepared for comparison to an optical scan of the corresponding tooth. For surgical intervention, a dry dentate mandible was scanned using a Scanora CBCT and the donor tooth was segmented. The donor tooth was repositioned, and two guides were designed. These tooth replica and guides were used in socket preparation of the dry mandible. The 3D computer model of the segmented teeth and related STL models showed satisfactory results with an acceptable accuracy. The surfaces were within 0·25mm distance, but in some areas up to 2·5mm deviation were seen. The results showed that 79% of the points was between 0·25 and -0·25mm, 3% was overestimated (>0·25mm) and 18% was underestimated (<-0·25mm). The computer-based repositioning of the donor tooth and construction of tooth replica and guide allowed socket preparation before donor tooth extraction and optimization of the STL procedure for in vivo planning of CBCT-based autotransplantation.

Occupational changes in manual tactile sensibility of the dentist.

The aim of this study was to find out if the use of vibrating tools (drill, ultrasonic scaler ...) in dental practice has negative side effects on the manual tactile sensibility of the dentist. The sensory tests were performed on 50 subjects, who were allocated to three different groups according to their occupation and the length of their working experience. The first test group consisted of 20 dentists, who had more than 25 years of work experience. As a control group, 20 non-dentists were recruited to obtain a similar age distribution as the former test group. A final group consisted of 10 dentists with more than 1 year of work experience. All subjects underwent three tests: light-touch sensation test, two-point discrimination test and thermal sensation test on the thumb and the index finger of the working and non-working hands. Results showed significant differences, especially for the light-touch sensation test. The study showed more specifically that the tactile sensibility of the working hand of the dentists with more than 25 years of work experience was significantly diminished with respect to the non-working hand and to the working hand of non-dentists. In the test group of young dentists, there was no noticeable reduction of manual tactile sensibility.

Reduction of Purkinje cell pathology in SCA1 transgenic mice by p53 deletion.

The expansion of a polyglutamine tract in the ataxin-1 protein beyond a critical threshold causes spinocerebellar ataxia type 1 (SCA1). To investigate the mechanism of neuronal degeneration in SCA1, we analyzed the phenotype of an SCA1 transgenic mouse model in the absence of p53, an important regulator of cell death. p53 deficiency did not affect the early features of SCA1 mice such as impaired motor coordination and ataxin-1 nuclear inclusion formation but caused a notable reduction in later pathological features, including Purkinje cell heterotopia, dendritic thinning, and molecular layer shrinkage. To determine if this protective effect was mediated by an anti-apoptotic property of p53 deficiency, we looked for apoptosis in SCA1 mice but failed to detect any evidence of it even in the presence of p53. We propose that p53 acts after the initial pathogenic events in SCA1 to promote the progression of neuronal degeneration in SCA1 mice, but this activity may be unrelated to apoptosis.

Evidence for stem-cell niches in the tracheal epithelium.

It is generally important to elucidate airway epithelial cell lineages and to identify multipotent progenitors as targets for gene therapy. Stem (S) cells are typically present in specialized compartments spatially proximal to their differentiated progeny, but an equivalent paradigm has not been demonstrated in the airway. We discovered a distinct population of cells displaying high levels of keratin expression in murine tracheal submucosal gland ducts, and tested the hypothesis that bromodeoxyuridine (BrdU) label-retaining cells (LRCs), thought to represent the S-cells, were present in this compartment. Mice received weekly epithelial damage by intratracheal detergent or SO(2) inhalation for 4 wk and received intraperitoneal injections of BrdU every 48 h during the injury and repair period. At 3 and 6 d after injury, BrdU-positive epithelial cells were noted along the entire tracheal length in both basal and lumenal cell positions. At later time points (20 and 95 d) LRCs were localized to gland ducts in the upper trachea and to systematically arrayed foci in the lower trachea, typically near the cartilage-intercartilage junction. LRCs were not pulmonary neuroendocrine cells. Heterotopic tracheal grafts after surface epithelial removal demonstrated reconstitution of a surface-like epithelium from gland remnants. These results suggest that airway epithelial S cells are localized to specific niches.

Molecular genetics of Rett syndrome and clinical spectrum of MECP2 mutations.

Rett syndrome, a neurodevelopmental disorder that is a leading cause of mental retardation in females, is caused by mutations in the X-linked gene encoding methyl-CpG-binding protein 2 (MeCP2). MECP2 mutations have subsequently been identified in patients with a variety of clinical syndromes ranging from mild learning disability in females to severe mental retardation, seizures, ataxia, and sometimes neonatal encephalopathy in males. In classic Rett syndrome, genotype-phenotype correlation studies suggest that X chromosome inactivation patterns have a more prominent effect on clinical severity than the type of mutation. When the full range of phenotypes associated with MECP2 mutations is considered, however, the mutation type strongly affects disease severity. MeCP2 is a transcriptional repressor that binds to methylated CpG dinucleotides throughout the genome, and mutations in Rett syndrome patients are thought to result in at least a partial loss of function. Abnormal gene expression may thus underlie the phenotype. Discovering which genes are misregulated in the absence of functional MeCP2 is crucial for understanding the pathogenesis of this disorder and related syndromes.

Alcohol and murine acquired immunodeficiency syndrome suppression of resistance to Cryptosporidium parvum infection during modulation of cytokine production.

The effects of inoculation of LP-BM5 murine leukemia retrovirus and chronic ethanol (5% v/v) ingestion on immunomodulation and Cryptosporidium parvum infection in C57BL/6 female mice were evaluated. The intestinal mucosae of retrovirally immunosuppressed animals were heavily colonized by Cryptosporidium parasites, and oocysts shedding in the feces persisted throughout the duration of the study. Mortality was exacerbated by murine retrovirus infection alone and exacerbated with concomitant chronic alcohol feeding (42.8 and 69.4%). Chronic ethanol ingestion decreased production of interferon-gamma and soluble interleukin-2 receptor released in supernatants of splenocytes when stimulated with concanavalin A, compared with the control group. Decreased production of interferon-gamma and interleukin-2 receptor was further exacerbated due to retrovirus infection. Tumor necrosis factor production by splenocytes stimulated with lipopolysaccharide, however, was significantly increased because of retrovirus infection. LP-BM5 retrovirus infection alone as well as with concomitant ethanol feeding altered cytokine production, which might have led to immunodeficiency. These changes may help explain the enhanced persistence of Cryptosporidiosis.

Diet and ethanol modulate immune responses in young C57BL/6 mice.

Chronic ethanol (ETOH) ingestion adversely affects the immunocompetence of alcohol abusers. ETOH directly impairs host defense mechanisms and indirectly modulates immunocompetence by interfering with the nutritional status of the alcoholic. It is not clear from the current literature, however, to what extent ETOH, nutritional status, or the combination of the two factors modulates immune mechanisms in chronic alcoholics. To date, most animal studies investigating the immunotoxicity of ETOH have neglected the dietary factors, which may have masked additional immunotoxic effects of ETOH. To examine these dietary factors, we fed mice three liquid ETOH diets with different dietary sufficiencies for 7 weeks and investigated various immune responses. Spleen cell number and secretions of immunoreactive interleukin-2 and tumor necrosis factor were totally independent of the diet, being affected only by ETOH. Body, spleen, and thymus weights, interferon-gamma secretion, and natural killer cell and phagocytic activities were modulated by ETOH as well as by diet. Natural killer cell and phagocytic activities were also directly affected by the nutritional quality of the diet. These results suggest that animal diets used in experimental studies of ETOH-induced immunomodulation must be planned and controlled carefully in order to single out the direct effects that ETOH has on the host defense system.

Suppression by dietary alcohol of resistance to Cryptosporidium during murine acquired immune deficiency syndrome.

Significant immunological changes occur following LP-BM5 murine leukemia retrovirus infection as well as chronic alcohol consumption. Retrovirus infection which has proceeded to murine AIDS permitted persistent Cryptosporidium infection, while non-retrovirus infected mice were resistant. Dietary alcohol provided until the day before parasite challenge did not affect resistance in controls, but increased the numbers of oocysts in the feces of retrovirus suppressed mice. Mortality was significant in retrovirus infected mice, and exacerbated slightly by dietary ethanol, while all controls survived parasite challenge. The retrovirus infected mice had greatly reduced numbers of intestinal CD4+ T helper cells and IgA+ B cells, which may explain their loss of intestinal resistance. Clearly, the severely immunosuppressed animals with murine AIDS were more sensitive to alcohol consumption than uninfected controls. This suggests that alcohol can synergize with murine retrovirus infection to exacerbate loss of resistance to an opportunistic pathogen common in human AIDS patients.

Evaluation of multiple component relaxation training with developmentally disabled persons.

Prior studies evaluating the response of developmentally disabled persons to relaxation training procedures are largely limited to case study reports. Most often relaxation training procedures are vaguely described in these studies, and limited outcome measures are employed. In the present comparative group outcome study a specific progressive muscle relaxation training procedure was combined with auditory electromyographic (EMG) biofeedback, modeling, and reinforcement procedures in an attempt to teach relaxation skills to mentally retarded persons (N = 32) who functioned in the profound to mild range. The procedure was effective in reducing experimental group subjects' EMG levels, F (1,28) = 6.39, p less than .05, and activity level as measured with an interval recording behavior rating procedure, F (1,28) = 58.05, p less than .05. No effect was found on peripheral skin temperature. Additionally, no significant difference between the response of low functioning and high functioning subjects was seen indicating that intellectual level and adaptive behavior level failed to predict success in treatment. Scoring on a simple behavioral assessment designed to measure receptive language skills and modeling abilities thought to relate to relaxation training success also failed to correlate with outcome measures. The need to develop other predictors of relaxation training success with a mentally retarded population is discussed.