Evidence of high rates of undiagnosed asthma in central Ohio elementary schoolchildren.

BACKGROUND: In Ohio, 14.5% of 5- to 9-year-olds and 17.3% of 10- to 17-year-olds have asthma. Moreover, there is concern that these numbers may underestimate the true disease burden. We sought to evaluate variability in asthma rates and respiratory symptoms among central Ohio fourth graders as a means to assess potential undiagnosed and undertreated asthma and its determinants. METHODS: We recruited 13 central Ohio elementary schools representing a broad range of nonurban settings and surveyed fourth graders to estimate school-level physician-diagnosed asthma (PDA), respiratory morbidity, and home exposures to smoking and pets. We used generalized linear mixed models with random intercept for school to examine relationships among exposures, respiratory symptoms, and PDA. RESULTS: Across the 13 schools, 94% of students participated in the survey, and the estimated asthma prevalence rate was 10.2% (N = 101 of 987). An additional 41% reported not having PDA but then went on to report symptoms consistent with asthma potentially suggestive of undiagnosed asthma. Of students with PDA, 21% reported symptoms suggestive of poorly controlled asthma. High levels of secondhand smoke (SHS) exposure were associated both with PDA (p = .05) and with respiratory symptoms (p < .0001). Students who owned a cat or a bird were more likely to report respiratory symptoms (p = .02 and p = .04, respectively). CONCLUSIONS: We provide evidence that the already high childhood asthma public health burden in central Ohio may be underreported. Schools may be an ideal location to conduct screenings and implement environmental interventions oriented toward SHS and household pets that will yield respiratory morbidity benefits.

Dental findings and identification of undiagnosed hyperglycemia.

A change in the American Diabetes Association guidelines added hemoglobin A1c (HbA1c) to the assays for diabetes diagnosis, but evidence suggests that glucose vs. HbA1c criteria may identify different segments of the affected population. We previously demonstrated that oral findings offer an opportunity for the detection of undiagnosed abnormal fasting plasma glucose (FPG) among dental patients who present with diabetes risk factors. In this new cross-sectional study, we sought to extend these observations. The first goal, using data from 591 new participants, was to assess our previously identified hyperglycemia detection models when HbA1c is used for case definition. The second goal, using data from our total cohort of 1,097 participants, was to evaluate the models' performance regardless of whether an FPG or an HbA1c is used for diagnosis. The presence of ≥ 26% teeth with deep pockets or ≥ 4 missing teeth correctly identified 72% of pre-diabetes or diabetes cases in the HbA1c sample and 75% in the total population. The addition of a point-of-care HbA1c ≥ 5.7% increased correct identification to 87% and 90%, respectively. These results demonstrate the validity of our prediction models regardless of the test used for diabetes or pre-diabetes diagnosis in the clinical setting and underscore the contribution dentists can make.

Protein kinase C regulates ezrin-radixin-moesin phosphorylation in canine osteosarcoma cells.

The development of metastasis is the most significant cause of death for both canine and human patients with osteosarcoma (OS). Ezrin has been associated with tumour progression and metastasis in human, canine and murine OS. Ezrin activation is dynamically regulated by protein kinase C (PKC) during metastatic progression in human and murine OS. To include the dog in the development of therapeutics that target ezrin biology, we characterized four new canine OS cell lines and confirmed the relationship between PKC and ezrin in these cells. Three of four cell lines formed tumours in mice that were histologically consistent with OS. All cell lines were markedly aneuploid and expressed ezrin and PKC. Finally, both ezrin phosphorylation and cell migration were inhibited using a PKC inhibitor. These data suggest that an association between PKC-mediated activation of ezrin and the metastatic phenotype in canine OS cells.

Identification of unrecognized diabetes and pre-diabetes in a dental setting.

Many diabetic patients remain undiagnosed, and oral findings may offer an unrealized opportunity for the identification of affected individuals unaware of their condition. We recruited 601 individuals who presented for care at a dental clinic, were ≥40 years old, if non-Hispanic white, and ≥30 years old, if Hispanic or non-white, and had never been told they have pre-diabetes or diabetes. Those with at least one self-reported diabetes risk factor (N=535) received a periodontal examination and a point-of-care hemoglobin A1c (HbA1c) test. A fasting plasma glucose (FPG) test was used as the study outcome, signifying potential diabetes or pre-diabetes. Performance characteristics of simple models of dysglycemia (FPG≥100 mg/dL) identification were evaluated and optimal cut-offs identified. A model including only two dental variables had an estimated area under the receiver operating characteristic curve (AUC) of 0.65. The addition of a point-of-care HbA1c test improved the AUC to 0.79 (p<0.001). The presence of ≥26% deep pockets or ≥4 missing teeth correctly identified 73% of true cases; the addition of an HbA1c≥5.7% increased correct identification to 92%. Analysis of our data suggests that oral healthcare professionals have the opportunity to identify unrecognized diabetes and pre-diabetes in dental patients and refer them to a physician for further evaluation and care.

Toriello-Carey syndrome in a patient with a de novo balanced translocation [46,XY,t(2;14)(q33;q22)] interrupting SATB2.

Toriello-Carey syndrome (TCS; OMIM 217980) is a multiple congenital anomaly syndrome characterized by the common manifestations of corpus callosum agenesis, cardiac defects, cleft palate/Robin sequence, hypotonia, mental retardation, postnatal growth retardation and distinctive facial dysmorphology (including micrognathia, telecanthus, small nose and full cheeks). Both autosomal recessive and X-linked inheritance have been proposed, but chromosomal abnormalities involving disparate loci have also been detected in a small number of cases. We report a patient with classical features of TCS and an apparently balanced de novo translocation between chromosomes 2 and 14 [46,XY,t(2;14)(q33;q22)]. Molecular characterization revealed direct interruption of the special AT-rich sequence-binding protein-2 (SATB2) gene at the 2q33.1 translocation breakpoint, while the 14q22.3 breakpoint was not intragenic. SATB2 mutation or deletion has been associated with both isolated and syndromic facial clefting; however, an association with TCS has not been reported. SATB2 functions broadly as a transcription regulator, and its expression patterns suggest an important role in craniofacial and central nervous system development, making it a plausible candidate gene for TCS.

Chromosome painting shows that skunks (Mephitidae, Carnivora) have highly rearranged karyotypes.

The karyotypic relationships of skunks (Mephitidae) with other major clades of carnivores are not yet established. Here, multi-directional chromosome painting was used to reveal the karyological relationships among skunks and between Mephitidae (skunks) and Procyonidae (raccoons). Representative species from three genera of Mephitidae (Mephitis mephitis, 2n = 50; Mephitis macroura, 2n = 50; Conepatus leuconotus, 2n = 46; Spilogale gracilis, 2n = 60) and one species of Procyonidae (Procyon lotor, 2n = 38) were studied. Chromosomal homology was mapped by hybridization of five sets of whole-chromosome paints derived from stone marten (Martes foina, 2n = 38), cat, skunks (M. mephitis; M. macroura) and human. The karyotype of the raccoon is highly conserved and identical to the hypothetical ancestral musteloid karyotype, suggesting that procyonids have a particular importance for establishing the karyological evolution within the caniforms. Ten fission events and five fusion events are necessary to generate the ancestral skunk karyotype from the ancestral carnivore karyotype. Our results show that Mephitidae joins Canidae and Ursidae as the third family of carnivores that are characterized by a high rate of karyotype evolution. Shared derived chromosomal fusion of stone marten chromosomes 6 and 14 phylogenetically links the American hog-nosed skunk and eastern spotted skunk.

T-lymphocyte production of macrophage inflammatory protein-1alpha is critical to the recruitment of CD8(+) T cells to the liver, lung, and spleen during graft-versus-host disease.

To investigate the mechanism by which macrophage inflammatory protein-1alpha (MIP-1alpha) affects graft-versus-host disease (GVHD), the expression and function of MIP-1alpha in 2 murine models of GVHD were evaluated. In irradiated class I and class II disparate recipients, the expression of messenger RNA (mRNA) and protein for MIP-1alpha was significantly increased in GVHD target organs after transfer of allogeneic lymphocytes compared to syngeneic lymphocytes. When lymphocytes unable to make MIP-1alpha were transferred, there was a decrease in the production of MIP-1alpha in the liver, lung, and spleen of bm1 (B6.C-H2(bm1)/By) and bm12 (B6.C-H2(bm12)/KhEg) recipients compared to the transfer of wild-type splenocytes. At day 6 there was a 4-fold decrease in the number of transferred CD8(+) T cells in the lung and approximately a 2-fold decrease in the number of CD8(+) T cells in the liver and spleen in bm1 recipients after transfer of MIP-1alpha-deficient (MIP-1alpha(-/-)) splenocytes compared to wild-type (MIP-1alpha(+/+)) splenocytes. These differences persisted for 13 days after splenocyte transfer. In contrast, the number of donor CD4(+) T cells found in the liver and lung was significantly increased after the transfer of MIP-1alpha(-/-) compared to wild-type splenocytes in bm12 recipients from day 6 through day 10. Thus, the transfer of allogeneic T cells was associated with the enhanced expression of MIP-1alpha in both a class I and class II mismatch setting. However, the increased expression only led to enhanced recruitment of CD8(+), but not CD4(+), donor T cells. Production of MIP-1alpha by donor T cells is important in the occurrence of GVHD and functions in a tissue-dependent fashion.

Constitutional inversion of chromosome 7 and hematologic cancers.

Nonrandom aberrations of chromosome 7 have been described in various hematopoietic disorders. We describe here two unrelated families with the same constitutional inversion of chromosome 7 [inv(7)(q11.2q22)]. The probands in both families had acute leukemia and cytogenetic analysis revealed that the inversion was the sole cytogenetic abnormality in the bone marrow at diagnosis. There is a history of hematologic diseases in one of these families that included a son who is a carrier of this constitutional inversion. The distal inversion breakpoint lies within the common region of chromosome loss identified in some myeloid diseases. These observations raise the possibility that this inherited chromosome rearrangement could result in a mutation of a tumor suppressor gene and possibly represent a predisposing event for the development of leukemia in these individuals.

The amateur Radio Emergency Service (ARES) and the National Disaster Medical System (NDMS).

The rescue, treatment, and evacuation of thousands of patients from a natural disaster or armed conflict that is coordinated by the National Disaster Medical System must be performed in accordance to health care standards recognized in this country. Without an effective communication system, morbidity and mortality will needlessly rise. A medical communication protocol that addresses this problem is proposed.

Adolescents' drinking and perceptions of legal and informal sanctions. A test of four hypotheses.

Peer disapproval contributed most and parental disapproval least to explaining adolescents' drinking behavior. Adolescents' moral commitment to laws and their perception of the certainty of legal sanctions had intermediate effects.

Religiosity, beliefs, normative standards and adolescent drinking.

Protestants were more likely than Catholics, religious adolescents were more likely than the nonreligious, and adolescents who believe that drinking is a sin were far more likely than adolescents who did not share that belief to disapprove of drinking and to abstain from drinking.