Combined microcystic adnexal carcinoma and squamous cell carcinoma arising in the ovarian cystic teratoma--a brief case report.

Malignant transformation of mature cystic teratoma of the ovary can develop with an incidence of 1-2%. Squamous cell carcinoma is the most common malignant tumor arising in benign cystic teratoma. The authors have recently experienced a case of combined microcystic adnexal carcinoma and squamous cell carcinoma arising in a benign cystic teratoma of the ovary in a 72-year-old Korean woman. The right ovarian cystic mass had been ruptured and firmly adhered with salpinx and omental fat tissue on operation. Thickened cystic wall with yellowish white solid infiltrative lesion was noted grossly, and two different malignant tumors of microcystic adnexal carcinoma exhibiting both eccrine and hair follicular differentiation and squamous cell carcinoma were observed microscopically. PAS and CEA positivities suggested eccrine differentiation in areas of microcystic adnexal carcinoma.     

Virus-induced diabetes mellitus: VIII. Passage of encephalomyocarditis virus and severity of diabetes in susceptible and resistant strains of mice.

The diabetogenic capacity of the M-variant of encephalomyocarditis (EMC) virus was markedly diminished after passage in mouse kidney cell cultures. One passage in mice fully restored this capacity. Virus harvested after five passages in either susceptible (SWR/J) or resistant (C57BL/6J) strains of mice was capable of producing diabetes in susceptible SWR/J mice but not in resistant C57BL/6J mice. Resistance was not overcome by inoculating mice with high concentrations of virus. Immunofluorescence studies showed that islets from strains of mice (i.e. CBA, AKR, C57BL/6J, A/J) that did not develop diabetes after infection with EMC virus, nonetheless, contained virus antigens. The percentage of cells in the islets containing virus antigens varied from 3-6% in CBA to 13-5% in A/J. In contrast 38% of the islet cells in susceptible SWR/J mice contained virus antigens. It is concluded that both the genetic background of the host and the passage history of the virus influence the development of diabetes.     

Development of a non-transformed human liver cell line with differentiated-hepatocyte and urea-synthetic functions: applicable for bioartificial liver

There is a need to develop human hepatocyte cell lines which retain both replicating capacity and highly differentiated functions to facilitate the development of an efficient bioartificial liver. The present study was undertaken to differentiate, using sodium butyrate, the actively replicating immortalized human liver cell line. The effects of butyrate on cell growth and cell cycle were analyzed, and the albumin synthesis, cytochrome P450 and ammonia-detoxifying activity of the butyrate-treated cells were measured. Butyrate treatment resulted in G2/M arrest of the cell cycle and polygonal changes in the cell morphology. Neither the control nor the butyrate-treated cells showed transformed characteristics. Butyrate treatment increased the amount of albumin secretion, cytochrome P450 activity, and the urea production rate of the cells. The present study provides non-transformed human hepatocytes, which can replicate unlimitedly and then restore differentiated hepatocyte-specific functions by butyrate, and therefore, have applications for the development of an efficient bioartificial liver.     

Multiple imputation technique applied to appropriateness ratings in cataract surgery

Missing data such as appropriateness ratings in clinical research are a common problem and this often yields a biased result. This paper aims to introduce the multiple imputation method to handle missing data in clinical research and to suggest that the multiple imputation technique can give more accurate estimates than those of a complete-case analysis. The idea of multiple imputation is that each missing value is replaced with more than one plausible value. The appropriateness method was developed as a pragmatic solution to problem of trying to assess "appropriate" surgical and medical procedures for patients. Cataract surgery was selected as one of four procedures that were evaluated as a part of the Clinical Appropriateness Initiative. We created mild to high missing rates of 10%, 30% and 50% and compared the performance of logistic regression in cataract surgery. We treated the coefficients in the original data as true parameters and compared them with the other results. In the mild missing rate (10%), the deviation from the true coefficients was quite small and ignorable. After removing the missing data, the complete-case analysis did not reveal any serious bias. However, as the missing rate increased, the bias was not ignorable and it distorted the result. This simulation study suggests that a multiple imputation technique can give more accurate estimates than those of a complete-case analysis, especially for moderate to high missing rates (30 - 50%). In addition, the multiple imputation technique yields better accuracy than a single imputation technique. Therefore, multiple imputation is useful and efficient for a situation in clinical research where there is large amounts of missing data.     

Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

Age-dependent changes of gene expression in the Drosophila head

Previous gene expression profiling studies in Drosophila have provided clues for understanding the aging process at the gene expression level. For a detailed understanding, studies of specific regions of the body are necessary. We therefore employed microarray analysis to examine gene expression changes in the Drosophila head during aging. Six hundred and eighty-four of the 5405 genes present in the microarray showed significant age-dependent changes as determined by significance analysis of microarray (SAM) (q < 0.05). The biological significance of the changes was analyzed using the gene annotations provided by the Gene Ontology Consortium. Major changes involved genes affecting energy metabolism (proton transport, energy pathways, oxidative phosphorylation) and neuronal function, especially responses to light. Genes involved in protein catabolism and several other metabolic processes also showed age-dependent changes. Most of the changes were reductions in gene expression and occurred before day 13 of adult life. After day 13, the age-dependent gene expression changes were relatively smaller than earlier life. Interestingly, the two biological processes of major gene expression changes are related to the two known environmental changes that increase life span in Drosophila: caloric restriction and light reduction. Our findings suggest that light signaling and energy metabolism may be important biological processes affected by aging and be interesting targets for the further investigation related to the longevity in Drosophila.     

Precision Tracing of Household Dengue Spread Using Inter- and Intra-Host Viral Variation Data,Kamphaeng Phet,Thailand

Dengue control approaches are best informed by granular spatial epidemiology of these viruses, yet reconstruction of inter- and intra-household transmissions is limited when analyzing case count, serologic, or genomic consensus sequence data. To determine viral spread on a finer spatial scale, we extended phylogenomic discrete trait analyses to reconstructions of house-to-house transmissions within a prospective cluster study in Kamphaeng Phet, Thailand. For additional resolution and transmission confirmation, we mapped dengue intra-host single nucleotide variants on the taxa of these time-scaled phylogenies. This approach confirmed 19 household transmissions and revealed that dengue disperses an average of 70 m per day between households in these communities. We describe an evolutionary biology framework for the resolution of dengue transmissions that cannot be differentiated based on epidemiologic and consensus genome data alone. This framework can be used as a public health tool to inform control approaches and enable precise tracing of dengue transmissions.     

Costs of Immunization Programs for 10 Vaccines in 94 Low- and Middle-Income Countries From 2011 to 2030

ObjectivesUnderstanding the level of investment needed for the 2021-2030 decade is important as the global community faces the next strategic period for vaccines and immunization programs. To assist with this goal, we estimated the aggregate costs of immunization programs for ten vaccines in 94 low- and middle-income countries from 2011 to 2030.MethodWe calculated vaccine, immunization delivery and stockpile costs for 94 low- and middle-income countries leveraging the latest available data sources. We conducted scenario analyses to vary assumptions about the relationship between delivery cost and coverage as well as vaccine prices for fully self-financing countries.ResultsThe total aggregate cost of immunization programs in 94 countries for 10 vaccines from 2011 to 2030 is $70.8 billion (confidence interval: $56.6-$93.3) under the base case scenario and $84.1 billion ($72.8-$102.7) under an incremental delivery cost scenario, with an increasing trend over two decades. The relative proportion of vaccine and delivery costs for pneumococcal conjugate, human papillomavirus, and rotavirus vaccines increase as more countries introduce these vaccines. Nine countries in accelerated transition phase bear the highest burden of the costs in the next decade, and uncertainty with vaccine prices for the 17 fully self-financing countries could lead to total costs that are 1.3-13.1 times higher than the base case scenario.ConclusionResource mobilization efforts at the global and country levels will be needed to reach the level of investment needed for the coming decade. Global-level initiatives and targeted strategies for transitioning countries will help ensure the sustainability of immunization programs.     

Systemic inflammation response index predicts all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis

International Urology and Nephrology - A systemic inflammation response index (SIRI) has been recently introduced as a tool for the assessment of the prognosis of several critical medical...