TRPM8 Mediates Hyperosmotic Stimuli-Induced Nociception in Dental Afferents.

Hyperosmolar sweet foods onto exposed tooth dentin evoke sudden and intense dental pain, called dentin hypersensitivity. However, it remains unclear how hyperosmolar stimuli excite dental primary afferent (DPA) neurons and thereby lead to dentin hypersensitivity. This study elucidated whether TRPM8, which is well known as a cold temperature- or menthol-activated receptor, additionally mediates nociception in response to hyperosmolar stimuli in adult mouse DPA neurons, which are identified by a fluorescent retrograde tracer: DiI. Single-cell reverse transcription polymerase chain reaction revealed that TRPM8 was expressed in subsets of DPA neurons and that TRPM8 was highly colocalized with TRPV1 and Piezo2. Immunohistochemical analysis also confirmed TRPM8 expression in DPA neurons. By using Fura-2-based calcium imaging, application of hyperosmolar sucrose solutions elicited calcium transients in subsets of the trigeminal ganglion neurons, which was significantly abolished by a selective TRPM8 antagonist: N-(3-Aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)benzamide (AMTB) hydrochloride. When we further examined changes of c-fos expression (a neuronal activation marker) in the spinal trigeminal nucleus after hyperosmolar stimulation onto exposed tooth dentin, c-fos mRNA and protein expression were increased and were also significantly reduced by AMTB, especially in the spinal trigeminal interpolaris-caudalis transition zone (Vi/Vc). Taken together, our results provide strong evidence that TRPM8 expressed in DPA neurons might mediate dental pain as a hyperosmosensor in adult mice.

Spin-induced band modifications of graphene through intercalation of magnetic iron atoms.

Intercalation of magnetic iron atoms through graphene formed on the SiC(0001) surface is found to induce significant changes in the electronic properties of graphene due mainly to the Fe-induced asymmetries in charge as well as spin distribution. From our synchrotron-based photoelectron spectroscopy data together with ab initio calculations, we observe that the Fe-induced charge asymmetry results in the formation of a quasi-free-standing bilayer graphene while the spin asymmetry drives multiple spin-split bands. We find that Fe adatoms are best intercalated upon annealing at 600 °C, exhibiting split linear π-bands, characteristic of a bilayer graphene, but much diffused. Subsequent changes in the C 1s, Si 2p, and Fe 3p core levels are consistently described in terms of Fe-intercalation. Our calculations together with a spin-dependent tight binding model ascribe the diffuse nature of the π-bands to the multiple spin-split bands originated from the spin-injected carbon atoms residing only in the lower graphene layer.

Risk factors for hospital and long-term mortality of critically ill elderly patients admitted to an intensive care unit.

BACKGROUND: Data on long-term outcomes of elderly (≥65 years) patients in ICU are sparse. MATERIALS AND METHODS: Adult patients (n = 1563, 45.4% elderly) admitted over 28 months were analyzed by competing risks regression model to determine independent factors related to in-hospital and long-term mortality. RESULTS: 414 (26.5%) and 337 (21.6%) patients died in-hospital and during the 52 months following discharge, respectively; the elderly group had higher mortality during both periods. After discharge, elderly patients had 2.3 times higher mortality compared to the general population of the same age-group. In-hospital mortality was independently associated with mechanical ventilation (subdistribution hazard ratio (SHR) 2.74), vasopressors (SHR 2.56), neurological disease (SHR 1.77), and Mortality Prediction Model II score (SHR 1.01) regardless of age and with malignancy (SHR, hematological 3.65, nonhematological 3.4) and prior renal replacement therapy (RRT, SHR 2.21) only in the elderly. Long-term mortality was associated with low hemoglobin concentration (SHR 0.94), airway disease (SHR 2.23), and malignancy (SHR hematological 1.11, nonhematological 2.31) regardless of age and with comorbidities especially among the nonelderly. CONCLUSIONS: Following discharge, elderly ICU patients have higher mortality compared to the nonelderly and general population. In the elderly group, prior RRT and malignancy contribute additionally to in-hospital mortality risk. In the long-term, comorbidities (age-related), anemia, airway disease, and malignancy were significantly associated with mortality.

Molecular genetic, cardiac and neurodevelopmental findings in cases of prenatally diagnosed rhabdomyoma associated with tuberous sclerosis complex.

OBJECTIVE: Rhabdomyoma is the most common type of cardiac tumor in fetuses and is often associated with tuberous sclerosis complex (TSC) with neurologic sequelae. The purpose of this study was to investigate the cardiac and neurodevelopmental outcomes of fetal rhabdomyoma. METHODS: We reviewed the clinical characteristics of 23 cases of cardiac rhabdomyoma diagnosed prenatally by fetal echocardiography at the Asan Medical Center between January 1998 and December 2009. We also reviewed postnatal results of brain magnetic resonance imaging, echocardiography, renal ultrasound examination and molecular genetic analysis to confirm the presence of cardiac rhabdomyoma with or without TSC. RESULTS: Among 23 cases, outcome data were available for 17 (73.9%) and six cases (26.1%) were lost to follow-up. The survival rate was 100.0% (17/17). Among the 17 cases with outcome data, spontaneous tumor regression occurred in eight (47.1%), and no change in tumor size and number was observed in the remaining nine cases (52.9%). There was no evidence of long-term cardiac dysfunction caused by persisting rhabdomyomas, regardless of tumor size. TSC was found in nine patients (52.9%), of whom five (55.6%) showed neurodevelopmental morbidity. We identified mutations in one of the TSC1 or TSC2 genes in four of nine TSC infants whose parents allowed us to perform molecular genetic analysis. Three of these (75.0%) were found to have neurologic impairment. Seven (77.8%) of nine TSC cases were non-familial. CONCLUSIONS: The overall outcome of isolated cardiac rhabdomyoma appears to be favorable. We suggest that systematic postnatal evaluation of TSC be performed even in cases of cardiac rhabdomyoma without a family history of TSC. Molecular characterization of TSC1 and TSC2 might be helpful in predicting short- and long-term neurodevelopmental outcomes.

Four-dimensional ultrasound guidance of prenatal invasive procedures.

OBJECTIVE: Technological advances in ultrasonography have revolutionized prenatal diagnosis and treatment. Here we evaluate the effectiveness of using four-dimensional (4D) ultrasonography to guide prenatal invasive procedures. PATIENTS AND METHODS: Prenatal invasive procedures using 4D ultrasound were recorded prospectively in 93 cases: 10 amnioinfusions, 50 amniocenteses, 8 chorionic villus samplings (CVS) and 25 cordocenteses. The needle target site was first identified using the two-dimensional (2D) mode, and was then confirmed using the three-dimensional (3D) mode. The needle was inserted under 4D ultrasound guidance. After selecting the needle target site, the true position of the needle was determined in three planes ('real-time 3D targeting'). RESULTS: Using 4D ultrasound guidance, most procedures were performed within 5 min and with a 100% success rate, even in cases involving severe oligohydramnios (amniocentesis), thin placentas (CVS) or narrow umbilical veins (cordocentesis). Moreover, there were no serious complications during or after any procedure. CONCLUSIONS: 4D ultrasonography can be used to guide various prenatal invasive procedures offering clear information in all three planes. It is likely that such imaging will reduce the time taken to complete the procedures and reduce the risks associated with them. Published by John Wiley & Sons, Ltd.

Prenatal detection of mesoblastic nephroma by sonography and magnetic resonance imaging.

Congenital mesoblastic nephroma is the most common neonatal kidney tumor and surgical excision is almost always curative. We report the prenatal detection of congenital mesoblastic nephroma by sonography and magnetic resonance imaging. After birth, a right nephrectomy was performed and the baby recovered well.

The progression of mediastinal lymphangioma in utero.

We describe a case of mediastinal lymphangioma that suddenly progressed in utero. The initial sonographic impression was one of pericardial effusion while the follow-up examination revealed a mediastinal cystic mass. At 35 weeks of gestation preterm labor occurred. An ultrasound examination performed at this time demonstrated the mediastinal cyst with internal hemorrhage and fetal hydrops. The cystic mass was resected 5 days after birth. The diagnosis of lymphangioma was made from histological examination. The infant was followed up for 18 months and remained well. We recommend frequent prenatal sonographic follow-up when a localized fluid collection is, shown in the mediastinum.

Evaluation of the Heart To Heart Project: lessons from a community-based chronic disease prevention project.

PURPOSE: To present an evaluation of a 5-year, community-based, chronic disease prevention project managed by a state health department to determine whether the department could replicate similar previous projects that had received more funding and other resources. DESIGN: The evaluation used a matched comparison design and a review of archive and interview data. SETTING: Florence, South Carolina (population: 56,240). SUBJECTS: A random sample of 1642 persons in Florence (and 1551 in the comparison) who responded to a risk factor questionnaire and underwent a physical assessment; 70.7% of baseline subjects participated in the postintervention. Forty key persons were interviewed concerning project effectiveness. INTERVENTIONS BY PROJECT: Walk-a-thons, a speakers' bureau, media messages, restaurant food labeling, and cooking seminars. More than 31,000 participants were involved in 585 activities. MEASURES: Questionnaires focused on hypertension, obesity, high cholesterol, smoking, and exercise. Physical assessments determined lipid, lipoprotein, apolipoprotein, and blood pressure levels. Analysis of covariance was used for baseline and postintervention comparisons. Content analysis was used on archive and interview data. RESULTS: The project had a slightly favorable intervention effect on cholesterol and smoking, but failed to have an effect on other risk factors for cardiovascular disease. The project influenced community awareness, enlisted influential community members, and fostered linkages among local health services. CONCLUSIONS: Health departments can be instrumental in community risk reduction programming; however, they may not replicate projects having greater resources.

Optimization of an HP Scanjet for quantification of protein electrophoresis gels.

An inexpensive desktop scanner, the Hewlett-Packard Scanjet IIp (HP), has been optimized for analysis of protein electrophoresis gels by comparison with a calibrated laser densitometer (Laser). Images from both densitometers were transferred to a personal computer and analyzed with QGEL software. Without correction the HP response was often in poor agreement with the Laser. However, when the HP response to Coomassie blue stained gels and x-ray films was linearized using a HP software option called Emphasis, the HP results agreed with results from the Laser. For 2D gels scanned with appropriate Emphasis applied, spot integrated density values were a constant multiple of 1.8 +/- 0.3 times the corresponding Laser value for x-ray films (CV = 17%) and 2.1 +/- 0.5 for Coomassie blue stained gels (CV = 24%). The highest error was observed for density extremes. For proteins quantified relative to standards using sodium dodecyl sulfate-slab gel electrophoresis, the HP values were within 15% of the Laser values. Data is shown concerning linearity and reproducibility of response, optical density range (about 0 to 1.8 OD units), variability of the imaging field, and resolution of the HP.

Public policy, federalism, and AIDS.

The AIDS epidemic poses important challenges to the American political system. In the context of AIDS, relationships between the public and private sectors as well as those among federal, state, and local governments have had a significant impact in shaping the nations response to the epidemic. The character of health policy in the United States has in large part been determined by uncertainty regarding the appropriate role of the public sector and by persistent beliefs that the best solutions are private sector ones. Similarly, relationships across levels of government are clouded by concerns about the presumed excesses of centralized (federal) government and the widespread conviction that the most appropriate solutions are state and local ones. AIDS emerged as a public health issue at a point in the early 1980s when a new federal administration was calling for a reduction in public sector and federal responsibility for addressing health and social needs. Since that time, stronger public and federal leadership appears to be developing, and both are essential to forging the policy partnerships between the public and private sectors and across levels of government that are essential to the development of a comprehensive policy response to the AIDS epidemic.

The federal response to the AIDS epidemic.

The response of the U.S. government to the AIDS epidemic is reviewed within the context of health policy making in the U.S.A. in general and the reduced role of the federal government in domestic social programs in particular. This review involves multiple levels of government, the relationship of government to the private sector, the diffusion of authority within a federal system, the long delays in policy implementation because of the absence of mechanisms to deal with emergency situations, the tendency to fund the response to AIDS from reallocation of appropriated funds, thereby creating financial distress for existing programs. The federal response to AIDS is considered uncoordinated, insufficient and inadequate in particular with respect to the support of public health education and the financing of health care for AIDS patients. These are needed while a vaccine may still be years away.

Nutrition policy--from neglect and uncertainty to debate and action.

Until recent years, nutrition has received little attention in U.S. agriculture, food, and health policies. This circumstance is changing. In the late sixties and early seventies, reports of hunger and malnutrition sparked public reaction and a shift in policy. The White House Conference on Food, Nutrition and Health in 1971 prompted the Senate select Committee on Nutrition and Human Needs to address itself to this problem, with the result that the Food Stamp, child nutrition, WIC, and Nutrition for the Elderly programs were initiated or expanded. Then, in the mid-seventies, the Select Committee turned its attention to broader issues of nutrition and health and declared that the goal of any food system is the maintenance and improvement of nutritional health of the population. This objective emerged as public policy in the Food and Agriculture Act of 1977. As the Select Committee continued its work, problems of overnutrition became more apparent. The culmination of its studies was the issuance early in 1977 of the "Dietary Goals for the United States," designed to improve the nutrition and reduce health problems of the population. To that same end, the Select Committee has also made recommendations regarding food labeling and nutrition education.