Inequality in self-rated health among immigrants,their descendants and ethnic Danes: examining the role of socioeconomic position

Objectives  

We investigated inequalities in self-rated health between immigrants, their descendants, and ethnic Danes and explored mediation by socioeconomic position and interactions between country of origin and socioeconomic position.     

Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals

It is recognized that the pH of exposure solutions can influence the toxicity and bioaccumulation of ionizing compounds. The present study investigates whether it can be considered a general rule that an ionizable compound is more toxic and more bioaccumulative when in the neutral state. Three processes were identified to explain the behavior of ionizing compounds with changing pH: the change in lipophilicity when a neutral compound becomes ionized, electrical attraction, and the ion trap. The literature was screened for bioaccumulation and toxicity tests of ionizing organic compounds performed at multiple pH levels. Toxicity and bioconcentration factors (BCFs) were higher for acids at lower pH values, whereas the opposite was true for bases. The effect of pH was most pronounced when pH?-?pK(a) was in the range of -1 to 3 for acids, and -3 to 1 for bases. The factor by which toxicity and BCF changed with pH was correlated with the lipophilicity of the compound (log?K(OW) of the neutral compound). For both acids and bases, the correlation was positive, but it was significant only for acids. Because experimental data in the literature were limited, results were supplemented with model simulations using a dynamic flux model based on the Fick-Nernst-Planck diffusion equation known as the cell model. The cell model predicts that bases with delocalized charges may in some cases show declining bioaccumulation with increasing pH. Little information is available for amphoteric and zwitterionic compounds; however, based on simulations with the cell model, it is expected that the highest toxicity and bioaccumulation of these compounds will be found where the compounds are most neutral, at the isoelectric point.     

PAPSS2‐related brachyolmia: Clinical and radiological phenotype in 18 new cases

Brachyolmia is a skeletal dysplasia characterized by short spine‐short stature, platyspondyly, and minor long bone abnormalities. We describe 18 patients, from different ethnic backgrounds and ages ranging from infancy to 19 years, with the autosomal recessive form, associated with PAPSS2. The main clinical features include disproportionate short stature with short spine associated with variable symptoms of pain, stiffness, and spinal deformity. Eight patients presented prenatally with short femora, whereas later in childhood their short‐spine phenotype emerged. We observed the same pattern of changing skeletal proportion in other patients. The radiological findings included platyspondyly, irregular end plates of the elongated vertebral bodies, narrow disc spaces and short over‐faced pedicles. In the limbs, there was mild shortening of femoral necks and tibiae in some patients, whereas others had minor epiphyseal or metaphyseal changes. In all patients, exome and Sanger sequencing identified homozygous or compound heterozygous PAPSS2 variants, including c.809G>A, common to white European patients. Bi‐parental inheritance was established where possible. Low serum DHEAS, but not overt androgen excess was identified. Our study indicates that autosomal recessive brachyolmia occurs across continents and may be under‐recognized in infancy. This condition should be considered in the differential diagnosis of short femora presenting in the second trimester.     

Analysis of 3D Prints by X-ray Computed Microtomography and Terahertz Pulsed Imaging

Purpose

A 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI).

Methods

Printing was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined.

Results

A clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5?±?0.75% larger than designed; n?=?3).

Conclusions

The 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms.

     

Secondary immunodeficiency in lymphoproliferative malignancies

Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti‐inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections. The pathogenesis of immune deficiency secondary to lymphoproliferative malignancy is multifactorial including disease‐ and treatment‐related factors. Supportive treatment, including early vaccination, anti‐infective prophylaxis, and replacement immunoglobulin, plays a key role in preventing infections in MM and CLL. This article provides an overview of the basic immunology necessary to understand the pathogenesis of secondary immunodeficiency and the infectious complications in MM and CLL. We also discuss the evidence supporting the role of prophylactic replacement immunoglobulin treatment in patients with antibody failure secondary to MM and CLL and the indications for its use. Copyright © 2016 John Wiley & Sons, Ltd.