Place-of-residence errors on death certificates for two contiguous U. S. counties

BACKGROUND: Based on death certificate data, the Texas Department of Health Bureau of Vital Statistics calculates age adjusted all-cause mortality rates for each Texas county yearly. In 1998 the calculated rates for two adjacent Texas counties was disparate. These counties contain one city (Amarillo) and are identical in size. This study examined the accuracy of recorded county of residence for deaths in the two counties in 1998. In our jurisdiction, the county of residence is assigned by funeral homes. METHODS: A random sample of 20% of death certificates was selected. The accuracy of the county of residence was verified by using a large area map, Tax Appraisal District records, and U.S. Census Bureau databases. Inaccuracies in recording the county or zip code of residence was recorded. RESULTS: Eighteen of 354 (5.4%) death certificates recorded the incorrect county and 21 of 354 (5.9%) of death certificates recorded the zip code improperly. There was a 14.4% county recording error rate for one county compared to a 0.82% for the other county. The zip code error rate was similar for the two counties (5.9% vs. 5.8%). Of the county errors, 83% occurred for addresses within a zip code that contained addresses in both counties. CONCLUSION: This study demonstrated a large error rate (14%) in recording county of residence for deaths in one county. A similar rate was not seen in an adjacent county. This led to significant miscalculation of mortality rates for two counties. We believe that errors may have arisen in part from use of internet programs by funeral homes to assign the county of residence. With some of these programs, the county is determined by zip code, and when a zip code straddles two counties, the program automatically assigns the county whose name appears first in the alphabet. This type of error could be avoided if funeral homes determined the county of residence from Tax Appraisal District or Census Bureau records, both of which are available on the internet. This type of error could also be avoided if vital statistics offices verified the county and zip code of residence using official sources

Full Mouth Rehabilitation with Implant-Supported Prostheses for Severe Periodontitis: A Case Report

Oral rehabilitation for a patient with severe loss of alveolar bone and soft tissue resulting from severe periodontitis presents a challenge to clinicians. Replacing loosening natural teeth with fixed prostheses supported by dental implants often requires either gingival surgery or bone grafting. The outcome of the bone grafting is sometimes unpredictable and requires longer healing time and/ or multiple surgeries. The presence of periodontal inflammation and periapical lesions often delay the placement of bone grafts as well as dental implants. Here we present a clinical case of a patient undergone full mouth reconstruction with implant-supported fixed prostheses. We demonstrated that early placement of implants (three weeks after extractions) with minimal bone grafting may be an alternative to conventional bone grafting followed by implant placement. We believe that primary stability during implant placement may contribute to our success. In addition, composite resin gingival material may be indicated in cases of large fixed implant prostheses as an alternative to pink porcelain

Gene therapy restores dopamine transporter expression and ameliorates pathology in iPSC and mouse models of infantile parkinsonism

Most inherited neurodegenerative disorders are incurable, and often only palliative treatment is available. Precision medicine has great potential to address this unmet clinical need. We explored this paradigm in dopamine transporter deficiency syndrome (DTDS), caused by biallelic loss-of-function mutations in SLC6A3, encoding the dopamine transporter (DAT). Patients present with early infantile hyperkinesia, severe progressive childhood parkinsonism, and raised cerebrospinal fluid dopamine metabolites. The absence of effective treatments and relentless disease course frequently leads to death in childhood. Using patient-derived induced pluripotent stem cells (iPSCs), we generated a midbrain dopaminergic (mDA) neuron model of DTDS that exhibited marked impairment of DAT activity, apoptotic neurodegeneration associated with TNFα-mediated inflammation, and dopamine toxicity. Partial restoration of DAT activity by the pharmacochaperone pifithrin-μ was mutation-specific. In contrast, lentiviral gene transfer of wild-type human SLC6A3 complementary DNA restored DAT activity and prevented neurodegeneration in all patient-derived mDA lines. To progress toward clinical translation, we used the knockout mouse model of DTDS that recapitulates human disease, exhibiting parkinsonism features, including tremor, bradykinesia, and premature death. Neonatal intracerebroventricular injection of human SLC6A3 using an adeno-associated virus (AAV) vector provided neuronal expression of human DAT, which ameliorated motor phenotype, life span, and neuronal survival in the substantia nigra and striatum, although off-target neurotoxic effects were seen at higher dosage. These were avoided with stereotactic delivery of AAV2.SLC6A3 gene therapy targeted to the midbrain of adult knockout mice, which rescued both motor phenotype and neurodegeneration, suggesting that targeted AAV gene therapy might be effective for patients with DTDS

CRIM1 Complexes with ß-catenin and Cadherins, Stabilizes Cell-Cell Junctions and Is Critical for Neural Morphogenesis

In multicellular organisms, morphogenesis is a highly coordinated process that requires dynamically regulated adhesion between cells. An excellent example of cellular morphogenesis is the formation of the neural tube from the flattened epithelium of the neural plate. Cysteine-rich motor neuron protein 1 (CRIM1) is a single-pass (type 1) transmembrane protein that is expressed in neural structures beginning at the neural plate stage. In the frog Xenopus laevis, loss of function studies using CRIM1 antisense morpholino oligonucleotides resulted in a failure of neural development. The CRIM1 knockdown phenotype was, in some cases, mild and resulted in perturbed neural fold morphogenesis. In severely affected embryos there was a dramatic failure of cell adhesion in the neural plate and complete absence of neural structures subsequently. Investigation of the mechanism of CRIM1 function revealed that it can form complexes with ß-catenin and cadherins, albeit indirectly, via the cytosolic domain. Consistent with this, CRIM1 knockdown resulted in diminished levels of cadherins and ß-catenin in junctional complexes in the neural plate. We conclude that CRIM1 is critical for cell-cell adhesion during neural development because it is required for the function of cadherin-dependent junctions

Xnrs and Activin Regulate Distinct Genes during Xenopus Development: Activin Regulates Cell Division

BACKGROUND: The mesoderm of the amphibian embryo is formed through an inductive interaction in which vegetal cells of the blastula-staged embryo act on overlying equatorial cells. Candidate mesoderm-inducing factors include members of the transforming growth factor type β family such as Vg1, activin B, the nodal-related proteins and derrière. METHODOLOGY AND PRINCIPLE FINDINGS: Microarray analysis reveals different functions for activin B and the nodal-related proteins during early Xenopus development. Inhibition of nodal-related protein function causes the down-regulation of regionally expressed genes such as chordin, dickkopf and XSox17α/β, while genes that are mis-regulated in the absence of activin B tend to be more widely expressed and, interestingly, include several that are involved in cell cycle regulation. Consistent with the latter observation, cells of the involuting dorsal axial mesoderm, which normally undergo cell cycle arrest, continue to proliferate when the function of activin B is inhibited. CONCLUSIONS/SIGNIFICANCE: These observations reveal distinct functions for these two classes of the TGF-β family during early Xenopus development, and in doing so identify a new role for activin B during gastrulation

Population mixing and leukaemia in young people around the La Hague nuclear waste reprocessing plant

In order to investigate for an association between population mixing and the occurrence of leukaemia in young people (less than 25 years), a geographical study was conducted, for the years 1979 to 1998, in Nord Cotentin (France). This area experienced between the years 1978 and 1992 a major influx of workers for the construction of a nuclear power station and a new nuclear waste reprocessing unit. A population mixing index was defined on the basis of the number of workers born outside the French department of ‘La Manche’ and living in each ‘commune’, the basic geographical unit under study. The analyses were done with indirect standardisation and Poisson regression model allowing or not for extra-Poisson variation. Urban ‘communes’ were considered as the reference population. The Incidence Rate Ratio was 2.7 in rural ‘communes’ belonging to the highest tertile of population mixing (95% Bayesian credible interval, 95%BCI=1.2–5.9). A positive trend was observed among rural strata with increasing population mixing index (IRR for trend=1.4, 95%BCI=1.1–1.8). The risk became stronger for Acute Lymphoblastic Leukaemia in children 1–6 years old in the highest tertile of population mixing (IRR=5.5, 95%BCI=1.4–23.3). These findings provide further support for a possible infective basis of childhood leukaemia

Looking to the future of zebrafish as a model to understand the genetic basis of eye disease

In this brief commentary, we provide some of our thoughts and opinions on the current and future use of zebrafish to model human eye disease, dissect pathological progression and advance in our understanding of the genetic bases of microphthalmia, andophthalmia and coloboma (MAC) in humans. We provide some background on eye formation in fish and conservation and divergence across vertebrates in this process, discuss different approaches for manipulating gene function and speculate on future research areas where we think research using fish may prove to be particularly effective

Control of Cerebellar Long-Term Potentiation by P-Rex-Family Guanine-Nucleotide Exchange Factors and Phosphoinositide 3-Kinase

Long-term potentiation (LTP) at the parallel fibre-Purkinje cell synapse in the cerebellum is a recently described and poorly characterized form of synaptic plasticity. The induction mechanism for LTP at this synapse is considered reciprocal to "classical" LTP at hippocampal CA1 pyramidal neurons: kinases promote increased trafficking of AMPA receptors into the postsynaptic density in the hippocampus, whereas phosphatases decrease internalization of AMPA receptors in the cerebellum. In the hippocampus, LTP occurs in overlapping phases, with the transition from early to late phases requiring the consolidation of initial induction processes by structural re-arrangements at the synapse. Many signalling pathways have been implicated in this process, including PI3 kinases and Rho GTPases.We hypothesized that analogous phases are present in cerebellar LTP, and took as the starting point for investigation our recent discovery that P-Rex--a Rac guanine nucleotide exchange factor which is activated by PtdIns(3,4,5)P(3)--is highly expressed in mouse cerebellar Purkinje neurons and plays a role in motor coordination. We found that LTP evoked at parallel fibre synapses by 1 Hz stimulation or by NO donors was not sustained beyond 30 min when P-Rex was eliminated or Rac inhibited, suggesting that cerebellar LTP exhibits a late phase analogous to hippocampal LTP. In contrast, inhibition of PI3 kinase activity eliminated LTP at the induction stage.Our data suggest that a PI3K/P-Rex/Rac pathway is required for late phase LTP in the mouse cerebellum, and that other PI3K targets, which remain to be discovered, control LTP induction