[Telemedical care concepts for heart failure: status and future]. / Telemedizinische Versorgungskonzepte bei Herzinsuffizienz: Status und Zukunft.

Telemedical care concepts provide opportunities to improve the care of patients with chronic heart failure (CHF). The current state of telemedical technologies enables the effective monitoring of the disease. Germany is one of the first European countries with an entitlement to telemedical supporting care for CHF patients. The decision of the German Federal Joint Committee in 2020 to introduce telemedical supporting care for CHF patients marks a milestone. For the first time, a digital care procedure was included in the benefits catalogue of the statutory health insurance funds due to its proven benefits in terms of morbidity and mortality. Privately insured CHF patients have been entitled to these benefits since January 2024. Future developments, particularly with respect to artificial intelligence procedures in telemedicine, are promising but require more evidence. Further research, technological innovation and supportive policy frameworks are needed to realize the full potential of these approaches. Continued collaboration between healthcare professionals, technology developers and policy makers will be crucial in sustainably improving the care of heart failure patients with telemedicine.

Indoor heat exposure in Baltimore: does outdoor temperature matter?

Heat exposure of a population is often estimated by applying temperatures from outdoor monitoring stations. However, this can lead to exposure misclassification if residents do not live close to the monitoring station and temperature varies over small spatial scales due to land use/built environment variability, or if residents generally spend more time indoors than outdoors. Here, we compare summertime temperatures measured inside 145 homes in low-income households in Baltimore city with temperatures from the National Weather Service weather station in Baltimore. There is a large variation in indoor temperatures, with daily-mean indoor temperatures varying from 10 °C lower to 10 °C higher than outdoor temperatures. Furthermore, there is only a weak association between the indoor and outdoor temperatures across all houses, indicating that the outdoor temperature is not a good predictor of the indoor temperature for the residences sampled. It is shown that much of the variation is due to differences in the availability of air conditioning (AC). Houses with central AC are generally cooler than outdoors (median difference of - 3.4 °C) while those with no AC are generally warmer (median difference of 1.4 °C). For the collection of houses with central or room AC, there is essentially no relationship between indoor and outdoor temperatures, but for the subset of houses with no AC, there is a weak relationship (correlation coefficient of 0.36). The results presented here suggest future epidemiological studies of indoor exposure to heat would benefit from information on the availability of AC within the population.

First Search for Short-Baseline Neutrino Oscillations at HFIR with PROSPECT.

This Letter reports the first scientific results from the observation of antineutrinos emitted by fission products of ^{235}U at the High Flux Isotope Reactor. PROSPECT, the Precision Reactor Oscillation and Spectrum Experiment, consists of a segmented 4 ton ^{6}Li-doped liquid scintillator detector covering a baseline range of 7-9 m from the reactor and operating under less than 1 m water equivalent overburden. Data collected during 33 live days of reactor operation at a nominal power of 85 MW yield a detection of 25 461±283 (stat) inverse beta decays. Observation of reactor antineutrinos can be achieved in PROSPECT at 5σ statistical significance within 2 h of on-surface reactor-on data taking. A reactor model independent analysis of the inverse beta decay prompt energy spectrum as a function of baseline constrains significant portions of the previously allowed sterile neutrino oscillation parameter space at 95% confidence level and disfavors the best fit of the reactor antineutrino anomaly at 2.2σ confidence level.

Exposure to household air pollution from biomass-burning cookstoves and HbA1c and diabetic status among Honduran women.

Household air pollution from biomass cookstoves is estimated to be responsible for more than two and a half million premature deaths annually, primarily in low and middle-income countries where cardiometabolic disorders, such as Type II Diabetes, are increasing. Growing evidence supports a link between ambient air pollution and diabetes, but evidence for household air pollution is limited. This cross-sectional study of 142 women (72 with traditional stoves and 70 with cleaner-burning Justa stoves) in rural Honduras evaluated the association of exposure to household air pollution (stove type, 24-hour average kitchen and personal fine particulate matter [PM2.5 ] mass and black carbon) with glycated hemoglobin (HbA1c) levels and diabetic status based on HbA1c levels. The prevalence ratio (PR) per interquartile range increase in pollution concentration indicated higher prevalence of prediabetes/diabetes (vs normal HbA1c) for all pollutant measures (eg, PR per 84 µg/m3 increase in personal PM2.5 , 1.49; 95% confidence interval [CI], 1.11-2.01). Results for HbA1c as a continuous variable were generally in the hypothesized direction. These results provide some evidence linking household air pollution with the prevalence of prediabetes/diabetes, and, if confirmed, suggest that the global public health impact of household air pollution may be broader than currently estimated.

TP53 mutational status is predictive of pazopanib response in advanced sarcomas.

BACKGROUND: To investigate whether TP53 DNA mutational status impacts progression-free survival (PFS) in patients with advanced sarcomas (soft tissue sarcoma) treated with vascular endothelial growth factor receptors (VEGFR) inhibition. PATIENTS AND METHODS: We retrospectively reviewed 19 cases of patients treated at the Ohio State James Comprehensive Cancer Center with advanced sarcoma treated with VEGFR inhibition who also had next-generation sequencing of their tumors (via FoundationOne Heme panel). We evaluated TP53 as well as mutations that were observed in at least 20% of patients and evaluated its contribution to PFS using the Kaplan-Meier survival analysis of available radiology end points. RESULTS: Mutations that were observed in at least 20% of patients included TP53 and Rb1. Only TP53 was predictive of PFS in the context of VEGFR inhibition. The PFS of patients with TP53 mutations was significantly greater than TP53 wild-type tumors with the median PFS of 208 versus 136 days, respectively [P = 0.036, hazards ratio 0.38 (95% confidence interval 0.09-0.83)]. CONCLUSIONS: Mutations in TP53 may serve as a predictive biomarker of response to VEGFR inhibition in patients with advanced sarcoma. Larger, prospective studies are necessary to confirm these findings.

Low bone mineral density for age/osteoporosis in triple A syndrome-an overlooked symptom of unexplained etiology.

UNLABELLED: Triple A syndrome (alacrima, achalasia, adrenal failure, progressive neurodegenerative disease) is caused by mutations in the AAAS gene which encodes the protein alacrima achalasia adrenal insufficiency neurologic disorder (ALADIN). Our investigation suggests that low bone mineral density (BMD) for age/osteoporosis could be a common but overlooked symptom of unexplained etiology in this rare multisystemic disease. INTRODUCTION: The purpose of this study is to evaluate incidence and etiology of BMD for age/osteoporosis, a possibly overlooked symptom in triple A syndrome. METHODS: Dual-energy X-ray absorptiometry (DXA) of the femoral neck, total hip, lumbar spine, and radius, bone turnover markers, minerals, total alkaline phosphatase (ALP), 25-hydroxy vitamin D (25-OHD), 1,25-dihydroxy vitamin D (1,25-OH2D), intact parathyroid hormone (PTH), and adrenal androgens (dehydroepiandrosterone sulfate (DHEAS) and androstenedione) were measured in five male and four female patients. RESULTS: At time of diagnosis, low BMD for age was suspected on X-ray in seven of nine patients aged 2-11 years (not performed in two patients); normal levels of minerals and ALP were found in nine patients and low levels of adrenal androgens in eight patients (not measured in one patient). Reevaluation 5-35 years after introduction of 12 mg/m(2)/day hydrocortisone showed low BMD for age in two children, osteopenia in one, and osteoporosis in six adults. Normal levels of minerals, ALP, PTH, 1,25-OH2D, procollagen type 1, crosslaps, and osteocalcin were found in all patients. Low levels of adrenal androgens were found in all and 25OHD deficiency in six patients. Body mass index was <25 % for age and sex in eight of nine patients. CONCLUSION: Low BMD for age/osteoporosis in our patients probably is not a result of glucocorticoid therapy but could be the consequence of low level of adrenal androgens, neurological impairment causing physical inactivity, inadequate sun exposure, and protein malnutrition secondary to achalasia. Considering ubiquitous ALADIN expression, low BMD/osteoporosis may be a primary phenotypic feature of the disease. Besides optimizing glucocorticoid dose, physical activity, adequate sun exposure, appropriate nutrition, and vitamin D supplementation, therapy with DHEA should be considered.

[Long-term oxygen therapy (LTOT)--what should physicians, homecare-providers and health insurance companies know?]. / Die Langzeit-Sauerstoff-Therapie (LTOT) - Was sollten Arzt, Versorger und Krankenkasse wissen?

Long-term oxygen treatment (LTOT) has been demonstrated to improve prognosis in patients with chronic respiratory insufficiency. In terms of pathogenesis, improved oxygenation, reduction of pulmonary artery pressure as well as reduction of respiratory work are important. Since there are considerable differences between the LTOT systems, individually tailored therapy is needed. In particular, the mobility aspects of the patients must be taken into consideration. It is important to distinguish between stationary/mobile devices with a liquid oxygen system and stationary/mobile devices with oxygen concentrator. Oxygen titration should be performed in relation to rest and activity phases (e. g. 6 minute walk test) as well as in relation to the sleep phase. Employing devices with demand-controlled valves should be critically examined. This can be undertaken only under physician orders and requires continuous monitoring.

Changes in differential gene expression in fibroblast cells from patients with triple A syndrome under oxidative stress.

The triple A syndrome is a rare autosomal recessive disease caused by mutations in the AAAS gene, which encodes the nucleoporin ALADIN. Recently it was shown that ALADIN plays a role in the import of different factors into the nucleus, which prevent the cell from DNA damage and consecutive cell death under oxidative stress. In order to investigate the changes in differential gene expression in ALADIN-deficient or mutated cells under oxidative stress we used fibroblast cell cultures of triple A syndrome patients and compared these to controls. Analysis of 84 genes, which are associated with oxidative stress and antioxidant defense, showed that 7 genes were significantly and differentially regulated, namely BCL2/adenovirus E1B 19kD-interacting protein 3 (BNIP3), 24-dehydrocholesterol reduc-tase (DHCR24), dual specificity phosphatase 1 (DUSP1), forkhead box M1 (FOXM1), nudix-type motif 1 (NUDT1), prostaglandin-endoperoxide synthase 2 (PTGS2), and scavenger receptor class A, member 3 (SCARA3). Whereas in control cells the expression of DHCR24, FOXM1, NUDT1, and SCARA3 was decreased after paraquat treatment, the expression did not change significantly in patient cells. However, the basal expression of SCARA3 and BNIP3 was significantly higher in patient cells than in controls whereas PTGS2 was less expressed. Furthermore, after paraquat treatment the expression of BNIP3, DUSP1, and PTGS2 was significantly increased in control cells while in patient cells the increase of DUSP1 and PTGS2 expression was significantly reduced. With this work we confirm that cells of triple A patients show an altered induction or downregulation of genes associated with oxidative stress and antioxidant defense.

Human dietary δ(15)N intake: representative data for principle food items.

Dietary analysis using δ(15)N values of human remains such as bone and hair is usually based on general principles and limited data sets. Even for modern humans, the direct ascertainment of dietary δ(15)N is difficult and laborious, due to the complexity of metabolism and nitrogen fractionation, differing dietary habits and variation of δ(15)N values of food items. The objective of this study was to summarize contemporary regional experimental and global literature data to ascertain mean representative δ(15)N values for distinct food categories. A comprehensive data set of more than 12,000 analyzed food samples was summarized from the literature. Data originated from studies dealing with (1) authenticity tracing or origin control of food items, and (2) effects of fertilization or nutrition on δ(15)N values of plants or animals. Regional German food δ(15)N values revealed no major differences compared with the mean global values derived from the literature. We found that, in contrast to other food categories, historical faunal remains of pig and poultry are significantly enriched in (15)N compared to modern samples. This difference may be due to modern industrialized breeding practices. In some food categories variations in agricultural and feeding regimens cause significant differences in δ(15)N values that may lead to misinterpretations when only limited information is available.

Impact of a cleaner-burning cookstove intervention on blood pressure in Nicaraguan women.

Few studies have evaluated the cardiovascular-related effects of indoor biomass burning or the role of characteristics such as age and obesity status, in this relationship. We examined the impact of a cleaner-burning cookstove intervention on blood pressure among Nicaraguan women using an open fire at baseline; we also evaluated heterogeneity of the impact by subgroups of the population. We evaluated changes in systolic and diastolic blood pressure from baseline to post-intervention (range: 273-383 days) among 74 female cooks. We measured indoor fine particulate matter (PM(2.5); N = 25), indoor carbon monoxide (CO; N = 32), and personal CO (N = 30) concentrations. Large mean reductions in pollutant concentrations were observed for all pollutants; for example, indoor PM(2.5) was reduced 77% following the intervention. However, pollution distributions (baseline and post-intervention) were wide and overlapping. Although substantial reductions in blood pressure were not observed among the entire population, a 5.9 mmHg reduction [95% confidence interval (CI): -11.3, -0.4] in systolic blood pressure was observed among women aged 40 or more years and a 4.6 mmHg reduction (95% CI: -10.0, 0.8) was observed among obese women. Results from this study provide an indication that certain subgroups may be more likely to experience improvements in blood pressure following a cookstove intervention.

Sterol regulatory element binding transcription factor 1 (SREBF1) polymorphism and milk fatty acid composition.

Milk is known to contain high concentrations of saturated fatty acids-such as palmitic (16:0), myristic (14:0), and lauric (12:0) acids-that can raise plasma cholesterol in humans, making their presence in milk undesirable. The main objective of our candidate gene study was to develop genetic markers that can be used to improve the healthfulness of bovine milk. The sterol regulatory element binding transcription factor 1 (SREBF1) known to regulate the transcription of lipogenic genes together with SREBF chaperone and insulin induced gene 1 were the candidate genes. The results showed significant association of the overall SREBF1 haplotypes with milk production and variations in lauric (12:0) and myristic (14:0) acid concentrations in milk. Haplotype H1 of SREBF1 was the most desirable to improve milk healthfulness because it was significantly associated with lower lauric (12:0) and myristic (14:0) acid concentrations compared with haplotype H3 of SREBF1, and lower lauric acid (12:0) concentration compared with haplotype H2 of SREBF1. Haplotype H1 of SREBF1, however, was significantly associated with lower milk production compared with haplotype H3 of SREBF1. We did not detect any significant associations between genetic polymorphisms in insulin induced gene 1 (INSIG1) and SREBF chaperone and milk fatty acid composition. In conclusion, genetic polymorphisms in SREBF1 can be used to develop genetic tools for the selection of animals producing milk with healthier fatty acid composition.

Association of polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) and fatty acid-binding protein-3 and fatty acid-binding protein-4 (FABP3 and FABP4) with fatty acid composition of bovine milk.

The main goal of this study was to develop tools for genetic selection of animals producing milk with a lower concentration of saturated fatty acids (SFA) and a higher concentration of unsaturated fatty acids (UFA). The reasons for changing milk fatty acid (FA) composition were to improve milk technological properties, such as for production of more spreadable butter, and milk nutritional value with respect to the potentially adverse effects of SFA on human health. We hypothesized that genetic polymorphisms in solute carrier family 27, isoform A6 (SLC27A6) fatty acid transport protein gene and fatty acid binding protein (FABP)-3 and FABP-4 (FABP3 and FABP4) would affect the selectivity of FA uptake into, and FA redistribution inside, mammary epithelial cells, resulting in altered FA composition of bovine milk. The objectives of our study were to discover genetic polymorphisms in SLC27A6, FABP3, and FABP4, and to test those polymorphisms for associations with milk FA composition. The results showed that after pairwise comparisons between SLC27A6 haplotypes for significantly associated traits, haplotype H3 was significantly associated with 1.37 weight percentage (wt%) lower SFA concentration, 0.091 lower SFA:UFA ratio, and 0.17 wt% lower lauric acid (12:0) concentration, but 1.37 wt% higher UFA and 1.24 wt% higher monounsaturated fatty acid (MUFA) concentrations compared with haplotype H1 during the first 3 mo of lactation. Pairwise comparisons between FABP4 haplotypes for significantly associated traits showed that haplotype H3 was significantly associated with 1.04 wt% lower SFA concentration, 0.079 lower SFA:UFA ratio, 0.15 wt% lower lauric acid (12:0), and 0.27 wt% lower myristic acid (14:0) concentrations, but 1.04 wt% higher UFA and 0.91 wt% higher MUFA concentrations compared with haplotype H1 during the first 3 mo of lactation. Percentages of genetic variance explained by H3 versus H1 haplotype substitutions for SLC27A6 and FABP4 ranged from 2.50 to 4.86% and from 4.91 to 7.22%, respectively. Tag single nucleotide polymorphisms were identified to distinguish haplotypes H3 of SLC27A6 and FABP4 from others encompassing each gene. We found no significant associations between FABP3 haplotypes and milk FA composition. In conclusion, polymorphisms in FABP4 and SLC27A6 can be used to select for cattle producing milk with lower concentrations of SFA and higher concentrations of UFA.

Spontaneous X chromosome MI and MII nondisjunction events in Drosophila melanogaster oocytes have different recombinational histories.

Recent studies of human oocytes have demonstrated an enrichment for distal exchanges among meiosis I (MI) nondisjunction events and for proximal exchanges among meiosis II (MII) events. Our characterization of 103 cases of spontaneous X chromosome nondisjunction in Drosophila oocytes strongly parallels these observations. The recombinational histories of MI (97/103) and MII (6/103) nondisjunctional ova were strikingly different. MI nondisjunction occurred primarily in oocytes with non-exchange X chromosomes; of the new nondisjoining exchange bivalents, most carried distal crossovers. Thus, spontaneous MI nondisjunction reflects the failure of the achiasmate segregation systems. MII nondisjunction occurred only in oocytes with proximal exchanges. We propose several models to explain how very proximal exchanges might impair proper segregation.

Particle release from refit operations in shipyards: Exposure, toxicity and environmental implications.

European harbours are known to contribute to air quality degradation. While most of the literature focuses on emissions from stacks or logistics operations, ship refit and repair activities are also relevant aerosol sources in EU harbour areas. Main activities include abrasive removal of filler and spray painting with antifouling coatings/primers/topcoats. This work aimed to assess ultrafine particle (UFP) emissions from ship maintenance activities and their links with exposure, toxicity and health risks for humans and the aquatic environment. Aerosol emissions were monitored during mechanical abrasion of surface coatings under real-world operating conditions in two scenarios in the Mallorca harbour (Spain). Different types of UFPs were observed: (1) highly regular (triangular, hexagonal) engineered nanoparticles (Ti-, Zr-, Fe-based), embedded as nano-additives in the coatings, and (2) irregular, incidental particles emitted directly or formed during abrasion. Particle number concentrations monitored were in the range of industrial activities such as drilling or welding (up to 5 ∗ 105/cm3, mean diameters <30 nm). The chemical composition of PM4 aerosols was dominated by metallic tracers in the coatings (Ti, Al, Ba, Zn). In vitro toxicity of PM2 aerosols evidenced reduced cell viability and a moderate potential for cytotoxic effects. While best practices (exhaust ventilation, personal protective equipment, dust removal) were in place, it is unlikely that exposures and environmental release can be fully avoided at all times. Thus, it is advisable that health and safety protocols should be comprehensive to minimise exposures in all types of locations (near- and far-field) and periods (activity and non-activity). Potential release to coastal surface waters of metallic engineered and incidental nanomaterials, as well as fine and coarse particles (in the case of settled dust), should be assessed and avoided.

Sensitivity and specificity of preoperative ultrasonography for diagnosing nodal metastases in patients with breast cancer.

PURPOSE: Rational therapy planning should aim to minimize the rate of axillary lymph node dissection (ALND) in patients without metastatic disease. By the same token, the frequency of sentinel lymph node biopsies (SLNB) should not be unnecessarily high in patients with axillary node disease. Preoperative axillary ultrasonography is a generally available noninvasive technique for assessing nodal status. MATERIALS AND METHODS: Based on retrospective data, we analyzed the sensitivity, specificity, positive and negative predictive value, and efficiency of preoperative ultrasonography US. A total of 429 axillary ultrasonographic examinations were included, and the management decisions were based on the ultrasonographic findings. Patients with suspicious US results were scheduled for ALND, while patients with unremarkable findings underwent SLNB. RESULTS: Axillary metastases were found in 146 of 429 (34 %) cases. In 75 of 429 (17 %) axillary examinations, ultrasonography revealed suspicious findings. In these cases, we proceeded with ALND, thereby reducing the number of SLNB by 17 %. 219 of 429 cases were classified correctly as not having metastasis, thus lowering the rate of ALND, which is associated with higher postoperative morbidity, by 51 %. Preoperative ultrasonography had a sensitivity of 53.6 %, specificity of 75.5 %, and a positive predictive value of 77.3 %. The negative predictive value was 51.3 % and the efficiency was 68.5 %. CONCLUSION: Ultrasonography is a moderately sensitive, but quite specific, preoperative method for assessing the axillary lymph nodes.

[Chronic pulmonary diseases: point of view of partners and their assessments with regard to the effects of lung sports]. / Chronische Lungenerkrankung: Sicht der Partner und deren Einschätzung bezüglich der Effekte von Lungensport.

BACKGROUND: Chronic diseases of the respiratory organs have, besides restrictions of lung function, also physical, mental and social consequences. The chronic disease impacts negatively not only the patient's own quality of life but also that of his/her partner and/or relative. As treatment modalities, besides drug therapy, above all outpatient rehabilitation measures have proved to be effective. In this pilot study we sought answers to three questions: (i) How is the quality of life of the patient's partner and/or relative influenced by the disease? How does the partner/relative assess the effect of the disease on the chronically ill patient? How does the partner/relative assess the effect of lung sports on the chronically ill patient? METHODS: A specially conceived questionnaire was given to the partners/relatives of 25 patients with chronic pulmonary diseases. The patients, 23 with chronic obstructive pulmonary disease and 2 with pulmonary fibrosis, have been participating in lung sports once a week for more than three years. The average age of the patients was 67 years. RESULTS: The patients' illness also negatively influenced the quality of life of the partner to a considerable extent. The impact of the patients' pulmonary disease on the healthy partner was assessed as being rather moderate. Restrictions of social life were essentially influenced by the amount of assistance required by the pulmonary patient. The therapeutic effects of lung sports on the well-being of the patient were aways considered to be positive by the respective partner/relatives. CONCLUSION: A chronic pulmonary illness also has a negative influence on the partner/relative's quality of life. The necessity for extensive assistance in daily life is accompanied by a considerable negative impact on the partner's quality of life. According to the opinion of the partner/relative, lung sports have positive effects in all of the chronically ill patient's fields of life.

Measurement of 227Ac impurity in 225Ac using decay energy spectroscopy.

225Ac is a valuable medical radionuclide for targeted α therapy, but 227Ac is an undesirable byproduct of an accelerator-based synthesis method under investigation. Sufficient detector sensitivity is critical for quantifying the trace impurity of 227Ac, with the 227Ac/225Ac activity ratio predicted to be approximately 0.15% by end-of-bombardment (EOB). Superconducting transition edge sensor (TES) microcalorimeters offer high resolution energy spectroscopy using the normal-to-superconducting phase transition to measure small changes in temperature. By embedding 225Ac production samples in a gold foil thermally coupled to a TES microcalorimeter we can measure the decay energies of the radionuclides embedded with high resolution and 100% detection efficiency. This technique, known as decay energy spectroscopy (DES), collapses several peaks from α decays into single Q-value peaks. In practice there are more complex factors in the interpretation of data using DES, which we will discuss herein. Using this technique we measured the EOB 227Ac impurity to be (0.142 ± 0.005)% for a single production sample. This demonstration has shown that DES is a useful tool for quantitative measurements of complicated spectra.

Chronic metabolic responses of postpartal dairy cows to subcutaneous glucagon injections, oral glycerol, or both.

We examined the long-term effects of daily subcutaneous injections of 15 mg of glucagon during the first 14 d postpartum with or without coadministration of 400 mL of pure glycerol orally on blood metabolites and hormones and liver composition of Holstein dairy cows during early lactation. Fourteen multiparous cows with body condition score of >or=3.5 points (1-5 point scale) were assigned randomly to one of 4 treatment groups-saline, glucagon, glycerol, or glucagon plus glycerol. Fatty liver syndrome was induced by feeding cows a dry-cow ration supplemented with 6 kg of cracked corn daily during the last 6 wk of the dry period. Compared with saline treatment (n=3), coadministration of glucagon and glycerol (n=4) increased plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations in both treatment weeks, whereas glucagon alone (n=3) produced similar changes plus a decrease in plasma beta-hydroxybutyrate in the second week only. No significant changes were observed for the glycerol alone treatment (n=4). We conclude that a single daily dose of glycerol for the first 14 d postpartum may potentiate the action of glucagon in the first treatment days to alleviate some symptoms of fatty liver syndrome, such as the increase in plasma nonesterified fatty acids and the decrease in plasma glucose and insulin, in Holstein dairy cows after parturition.

Autosomal dominant neurohypophyseal diabetes insipidus in two families. Molecular analysis of the vasopressin-neurophysin II gene and functional studies of three missense mutations.

BACKGROUND: Autosomal dominant familial neurohypophyseal diabetes insipidus (adFNDI) is a rare disease with symptoms of polydipsia, polyuria and dehydration caused by arginine vasopressin deficiency. Disease onset is within infancy or adolescence. A variety of disease-causing mutations of the arginine vasopressin neurophysin II gene (AVP) on chromosome 20p13 have been described. METHODS: Two Polish families with adFNDI were screened for mutations. Processing of wild-type (WT) and mutant AVP was monitored using immunocytochemical methods in stably transfected Neuro2A cells. AVP secretion into the cell culture supernatant was investigated with an enzyme immunoassay. RESULTS: In the first family a heterozygous p.G96D mutation was identified. Some patients additionally carried a novel heterozygous mutation p.A159T. The second family presented with a heterozygous mutation p.C98G. Confocal laser microscopy unveiled accumulation of p.G96D and p.C98G prohormones in the cellular bodies, whereas WT and p.A159T prohormones and/or processed products were located in the tips of cellular processes. Reduced levels of AVP in supernatant culture medium of p.G96D and p.C98G transfected cells in comparison to p.A159T and WT cells were found. CONCLUSIONS: We conclude that the p.G96D and p.C98G mutations cause adFNDI in the two reported families. The sequence variant p.A159T does not seem to have disease-causing effects.

Genetic analysis of familial non-syndromic primary failure of eruption.

OBJECTIVES: While some eruption disorders occur as part of a medical syndrome, primary failure of eruption (PFE) - defined as a localized failure of secondary tooth eruption - exists without systemic involvement. Recent studies support that heredity may play an important role in the pathogenesis of PFE. The objective of our human genetic study is to investigate the genetic contribution to PFE. MATERIALS AND METHODS: Four candidate genes POSTN, RUNX2, AMELX, and AMBN) were investigated because of their relationship to tooth eruption or putative relationship to each other. Families and individuals were ascertained based on the clinical diagnosis of PFE. Pedigrees were constructed and analyzed by inspection to determine the mode of inheritance in four families. The candidate genes were directly sequenced for both unrelated affected individuals and unaffected individuals. A genome wide scan using 500 microsatellite markers followed by linkage analysis was carried out for one family. RESULTS: Pedigree analysis of families suggests an autosomal dominant inheritance pattern with complete penetrance and variable expressivity. Sequence analysis revealed two non-functional polymorphisms in the POSTN gene and no other sequence variations in the remaining candidate genes. Genotyping and linkage analysis of one family yielded a LOD score of 1.51 for markers D13S272; D15S118 and D17S831 on chromosomes 13, 15 and 17 respectively. CONCLUSIONS: While LOD scores were not significant evidence of linkage, extension of current pedigrees and novel SNP chip technology holds great promise for identification of a causative locus for PFE.