Molecular probe dynamics and free volume heterogeneities in n-propanol confined in a regular MCM-41 matrix by ESR and PALS

A combined investigation of the spin probe TEMPO mobility and the free volume holes in n-propanol (n-PrOH) confined in a regular virgin MCM-41 matrix by means of ESR or PALS techniques, respectively, is reported. Dynamics of spin probe TEMPO alters at several characteristic ESR temperatures which are close to the characteristic PALS ones reflecting the changes in o-Ps annihilation and the related free volume. Correlations between these characteristic ESR and PALS temperatures indicate the common physical origins of the respective changes in the free volume expansion and the TEMPO mobility in the confined liquid n-PrOH. The significant difference in dynamic heterogeneity of TEMPO after confinement and free volume dispersion reflect the strongly altered structural-dynamic relationships in the confined n-PrOH medium with respect to the bulk situation.

A combined investigation of the spin probe TEMPO mobility and the free volume holes in n-propanol (n-PrOH) confined in a regular virgin MCM-41 matrix by means of ESR or PALS techniques, respectively, is reported.     

Maternal BMI Before Pregnancy, Maternal Weight Gain During Pregnancy, and Risk of Persistent Positivity for Multiple Diabetes-Associated Autoantibodies in Children With the High-Risk HLA Genotype: The MIDIA study

OBJECTIVE

To assess whether maternal BMI before pregnancy and weight gain during pregnancy predicted the risk of islet autoimmunity in genetically susceptible children.

RESEARCH DESIGN AND METHODS

Of 46,939 newborns screened for the high-risk HLA genotype DR4-DQ8/DR3-DQ2, 1,003 were positive and 885 were followed with serial blood samples tested for autoantibodies to insulin, GAD, and insulinoma-associated protein 2 (IA2). The end point was defined as repeated positivity for two or three autoantibodies or the onset of type 1 diabetes (islet autoimmunity).

RESULTS

Thirty-six children developed islet autoimmunity, of whom 10 developed type 1 diabetes. Both maternal BMI ≥30 kg/m² before pregnancy and maternal weight gain ≥15 kg predicted the increased risk of islet autoimmunity (hazard ratio [HR] 2.5, P = 0.023, and HR 2.5, P = 0.015, respectively), independent of maternal diabetes.

CONCLUSIONS

Maternal weight may predict risk of islet autoimmunity in offspring with a high genetic susceptibility for type 1 diabetes.Type 1 diabetes is caused by specific autoimmunity against pancreatic β-cells. The incidence of type 1 diabetes is increasing worldwide, and Norway currently has one of the world''s highest incidence rates (1,2). The etiology is multifactorial, determined by a combination of genetic and nongenetic factors. In Norway, 2.1% of newborns carry the HLA genotype DR4-DQ8/DR3-DQ2, which confers a relative risk for type 1 diabetes in excess of 20 and an estimated absolute risk of 7% by age 15 years (3,4). Nongenetic factors have been difficult to identify. Islet autoimmunity may start as early as in the 1st year of life before clinical type 1 diabetes with variable duration or even in utero (5). Studies have suggested that growth and obesity in childhood are associated with risk of type 1 diabetes and islet autoimmunity (6,7), but we are not aware of previous studies investigating the role of maternal BMI or weight gain in pregnancy.     

On crystallization of water confined in liposomes and cryoprotective action of DMSO

In this work, the phase behavior of cryoprotective mixtures based on dimethyl sulfoxide (DMSO) mixed with a lipid bilayer consisting of dimyristoyl phosphatidylcholine (DMPC) was studied. This system represented a model of a biological cell and its membrane. The aim of the work was to clarify the origin of the cryoprotective action of low-concentrated mixtures (1–10 vol%) DMSO in water, representing mixtures used in cryopreservation in cell therapy. The combination of experimental techniques of differential scanning calorimetry (DSC) and positron annihilation lifetime spectroscopy (PALS) allowed a study of crystallization behavior of water confined in liposomes imitating the intracellular environment. The ability of liposomes to show the fundamental aspects of water phase behavior seen during freezing of biological cells was proved. The presence of an amorphous freeze-concentrated phase of DMSO in the frozen state was confirmed and its possible crystallization into the DMSO trihydrate and ice during thawing was demonstrated. Correlation between the critical temperature range for the loss of cell viability during slow thawing and the temperatures of freeze-concentrated phase crystallization was found. Based on this finding, possible mechanisms of DMSO cryoprotection are discussed with support brought by results for the studied model system. Quantification of the ice phase fraction in the frozen mixtures revealed that even low concentrations of DMSO can induce a considerable decrease in the amount of ice present.

Ice-free phase formed by DMSO acting as a protective layer of lipid membrane.     

HHV-6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV-6 and fatal CMV pneumonitis

Two patients with the characteristic high human herpesvirus 6 (HHV-6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV-6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs. In contrast HHV-6 DNA was detected at high levels throughout the organs with the exception of donor-derived haematopoietic tissue. In individuals with chromosomal integration, HHV-6 DNA is found in every tissue of recipient origin indicating inheritance through the germ line.     

Obstetrics during Civil War: six months on a maternity ward in Mallavi,northern Sri Lanka

A long-term, large-scale ethnic armed conflict continues in Sri Lanka, where militant separatists control a northern section of the island. The conflict has resulted in a large population of internally displaced persons and a shortage of medical staff. Drug and equipment shortages compound the difficulty in access to medical care. This article reports the experiences from 1 November 2000 to 30 April 2001 recorded by review of medical records and by interviews, in the peripheral unit, in a separatist controlled area of the Mallavi maternity ward. There were 704 births. Most of the mothers had been displaced by the war (69.5 per cent) and had experienced food shortage (67.5 per cent). Referred patients (18.1 per cent) had a high rate of caesarean section (44.3 per cent) and had travelled a mean of 57.6 km to reach Mallavi. There had been substantial antenatal care (94.0 per cent), tetanus toxoid vaccination (95.1 per cent) and malaria prophylaxis (86.4 per cent). Risk factors for low birth weight included a maternal body mass index less than 19 (RR 1.55, CI 1.11-2.16, P = .011), primiparity (RR 1.44, CI 1.05-1.97, P = .024) and self-reported malarial infection during pregnancy (RR 1.42, CI 1.03-1.97, P = .036). Rates of low birth weight, stillbirths, neonatal deaths and maternal mortality in the Mallavi units were higher than the Sri Lankan national averages. Improvements in quality of care and access to health care are unlikely while the war continues.     

Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

Background  

Aberrant expression of myeloid antigens (MyAgs) on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases).