Race/Ethnicity, Educational Attainment, and Pregnancy Complications in New York City Women with Pre-existing Diabetes

Background: More women are entering pregnancy with pre-existing diabetes. Disease severity, glycaemic control, and predictors of pregnancy complications may differ by race/ethnicity or educational attainment, leading to differences in adverse pregnancy outcomes. Methods: We used linked New York City hospital record and birth certificate data for 6291 singleton births among women with pre-existing diabetes between 1995 and 2003. We defined maternal race/ethnicity as non-Hispanic white, non-Hispanic black, Hispanic, South Asian, and East Asian, and education level as 12 years. Our outcomes were pre-eclampsia, preterm birth (PTB) (<37 weeks gestation and categorised as spontaneous or medically indicated), as well as small-for-gestational age (SGA) and large-for-gestational age (LGA). Using multivariable binomial regression, we estimated the risk ratios for pre-eclampsia, SGA, and LGA. We used multivariable multinomial regression to estimate odds ratios (OR) for PTB. Results: Compared with non-Hispanic white women with pre-existing diabetes, non-Hispanic black and Hispanic women with pre-existing diabetes had a 1.50-fold increased risk of pre-eclampsia compared with non-Hispanic whites with pre-existing diabetes, after full adjustment. Non-Hispanic black and Hispanic women with pre-existing diabetes had adjusted ORs of 1.72 [adj. 95% confidence interval (CI) 1.38, 2.15] and 1.65 [adj.95% CI 1.32, 2.05], respectively, for medically indicated PTB. South Asian women with pre-existing diabetes had the highest risk for having an SGA infant [adj. OR: 2.29; adj. 95% CI 1.73, 3.03]. East Asian ethnicity was not associated with these pregnancy complications. Conclusions: Non-Hispanic black, Hispanic, and South Asian women with pre-existing diabetes may benefit from targeted interventions to improve pregnancy outcomes

Short-Term Insulin Requirements Following Gastric Bypass Surgery in Severely Obese Women with Type 1 Diabetes

Background: In severely obese type 2 diabetes patients, gastric bypass surgery (GB) reduces body mass index (BMI) and hemoglobin A1c (HbA1c) and allows reduced doses of insulin and other medications. Data regarding the effects of GB on severely obese patients with type 1 diabetes are limited. Methods: Severely obese women with type 1 diabetes (n = 9) were studied immediately before and after GB (7.7 ± 5.8 weeks, mean ± SD). Results: On average, GB reduced mean BMI by 11 % and mean HbA1c by 0.9 % (from 8.0 to 7.1 %), with a parallel 38 % decrease in basal insulin requirements (expressed per kilogram of body weight). Conclusion: GB rapidly decreased BMI, HbA1c, and insulin requirements in severely obese women with type 1 diabetes. However, physiologic insulin replacement remains necessary in patients with type 1 diabetes

Spray drying as a reliable route to produce metastable carbamazepine form IV

Carbamazepine is an active pharmaceutical ingredient used in the treatment of epilepsy that can form at least five polymorphic forms. Metastable form IV was originally discovered from crystallisation with polymer additives however has not been observed from subsequent solvent only crystallisation efforts. This work reports the reproducible formation of phase pure crystalline form IV by spray drying of methanolic carbamazepine solution. Characterisation of the material was carried out using diffraction, SEM and DSC. In situ Raman spectroscopy was used to monitor the spray dried product during the spray drying process. This work demonstrates spray drying provides a robust method for the production of form IV carbamazepine and the combination of high supersaturation and rapid solid isolation from solution overcomes the apparent limitation of more traditional solution crystallisation approaches to produce metastable crystalline forms

Correction: Population Genomics of the Immune Evasion (var) Genes of Plasmodium falciparum

Var genes encode the major surface antigen (PfEMP1) of the blood stages of the human malaria parasite Plasmodium falciparum. Differential expression of up to 60 diverse var genes in each parasite genome underlies immune evasion. We compared the diversity of the DBLalpha domain of var genes sampled from 30 parasite isolates from a malaria endemic area of Papua New Guinea (PNG) and 59 from widespread geographic origins (global). Overall, we obtained over 8,000 quality-controlled DBLalpha sequences. Within our sampling frame, the global population had a total of 895 distinct DBLalpha "types" and negligible overlap among repertoires. This indicated that var gene diversity on a global scale is so immense that many genomes would need to be sequenced to capture its true extent. In contrast, we found a much lower diversity in PNG of 185 DBLalpha types, with an average of approximately 7% overlap among repertoires. While we identify marked geographic structuring, nearly 40% of types identified in PNG were also found in samples from different countries showing a cosmopolitan distribution for much of the diversity. We also present evidence to suggest that recombination plays a key role in maintaining the unprecedented levels of polymorphism found in these immune evasion genes. This population genomic framework provides a cost effective molecular epidemiological tool to rapidly explore the geographic diversity of var genes

Affinity proteomics reveals elevated muscle proteins in plasma of children with cerebral malaria

Systemic inflammation and sequestration of parasitized erythrocytes are central processes in the pathophysiology of severe Plasmodium falciparum childhood malaria. However, it is still not understood why some children are more at risks to develop malaria complications than others. To identify human proteins in plasma related to childhood malaria syndromes, multiplex antibody suspension bead arrays were employed. Out of the 1,015 proteins analyzed in plasma from more than 700 children, 41 differed between malaria infected children and community controls, whereas 13 discriminated uncomplicated malaria from severe malaria syndromes. Markers of oxidative stress were found related to severe malaria anemia while markers of endothelial activation, platelet adhesion and muscular damage were identified in relation to children with cerebral malaria. These findings suggest the presence of generalized vascular inflammation, vascular wall modulations, activation of endothelium and unbalanced glucose metabolism in severe malaria. The increased levels of specific muscle proteins in plasma implicate potential muscle damage and microvasculature lesions during the course of cerebral malaria

American Indian Men\u27s Perceptions of Breast Cancer Screening for American Indian Women

Screening, especially screening mammography, is vital for decreasing breast cancer incidence and mortality. Screening rates in American Indian women are low compared to other racial/ethnic groups. In addition, American Indian women are diagnosed at more advanced stages and have lower 5-year survival rate than others. To better address the screening rates of American Indian women, focus groups (N=8) were conducted with American Indian men (N=42) to explore their perceptions of breast cancer screening for American Indian women. Our intent was to understand men’s support level toward screening. Using a community-based participatory approach, focus groups were audio-taped, transcribed verbatim, and analyzed using a text analysis approach developed by our team. Topics discussed included breast cancer and screening knowledge, barriers to screening, and suggestions to improve screening rates. These findings can guide strategies to improve knowledge and awareness, communication among families and health care providers, and screening rates in American Indian communities

Quality by design approach for early understanding of active pharmaceutical ingredient recovery process through dead-end filtration

This study applied some concepts of quality-by-design (QbD) approach for an early understanding of crystal recovery through filtration. A bespoke laboratory scale dead-end filtration platform (modified Biotage vacuum master (BVM) ≈ 50 mL working volume) was used to investigate the recovery of an active pharmaceutical ingredient (API) of different size distributions using acetaminophen crystals (micronised, medium-sized Bioxtra and coarse) as a case study. The method involved: (1) identification of critical process parameters (CPPs) with significant impact on process stability (a process risk evaluation step based on one factor at a time); (2) design of experiment to screen the influence of design factors (such as filter pore size, pressure difference, crystal loading and particle size distribution (PSD)) contributing to process instability based on process responses (volumetric flux and specific cake resistance); and (3) investigate the optimal process window for reduced probability of failure and process predictability. The filtration process responses were characterised by assessing the filtrate flow rate by the application of Darcy’s law. Initial assessments of process steadiness for acetaminophen crystals recovery shows that the filter pore size and API crystal sizes are critical. A non-linear process dependency was observed between the applied pressure difference, pore size, and crystal size. Screening crystal recovery conditions based on the design of experiment (DoE) approach indicated a steady filtration process for all crystal sizes tested except for coarse crystals which shows non-valid (negative) specific cake resistance at conditions of 5 µm pore size filter and 100 mbar pressure difference. However, pressure difference and pore size had a notable impact on the process responses. As a result, 10 µm pore size filter was used for investigating the optimal process window. Process predictability was demonstrated by data clustering and refinement based on partial least square model. The results showed good predictability with >98% regression between the predicted and experimental data. Verification of optimal operating window with less than 5% probability failure resulted in conditions of 300 – 450 mbar pressure difference and PSD of 45 – 110 µm. The approach studied using the small-scale BVM provided an early data gathering and systematic approach to understanding process interactions affecting crystal recovery through dead-end filtration