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Background Maternal vitamin D status during pregnancy and lactation is a modifiable factor that may influence offspring musculoskeletal outcomes. However, few randomized trials have tested the effects of prenatal or postpartum vitamin D supplementation on offspring bone and muscle development. Objectives The aim was to examine hypothesized effects of improvements in early-life vitamin D status on childhood musculoskeletal health in Dhaka, Bangladesh. Methods In a previously completed, double-blind, dose-ranging trial, healthy pregnant women (n  = 1300) were recruited at 17–24 weeks' gestation and randomly assigned to a prenatal/postpartum regimen of 0/0, 4200/0, 16,800/0, 28,000/0, or 28,000/28,000 IU cholecalciferol (vitamin D3)/wk until 26 wk postpartum. In this new report, we describe additional follow-up at 4 y of age (n  = 642) for longer-term outcomes. Bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by DXA. Grip strength was tested using a hand-held dynamometer. The primary comparison was children of women assigned to 28,000 IU/wk prenatally compared with placebo. Differences are expressed as means and 95% CIs. Results Total-body-less-head (TBLH) BMC, TBLH aBMD, and grip strength were similar in the combined high-dose prenatal (28,000/0 and 28,000/28,000 IU/wk) compared with placebo groups (mean difference [95% CI] = 0.61 g [–10.90, 12.13], 0.0004 g/cm2 [–0.0089, 0.0097], and 0.02 kg [–0.26, 0.31], respectively). In dose-ranging analyses, TBLH BMC and aBMD, whole-body BMC and aBMD, and grip strength in each of the prenatal vitamin D groups were not significantly different from placebo (P  > 0.05 for all comparisons). Only head aBMD was greater in children of women assigned to the 28,000/28,000-IU regimen compared with placebo (mean difference [95% CI] = 0.024 g/cm2 [0.0009, 0.047], P  = 0.042); the effect was attenuated upon adjustment for child height, weight, and sex (P  = 0.11). Conclusions Maternal prenatal, with or without postpartum, vitamin D supplementation does not improve child BMC, aBMD, or grip strength at 4 y of age. The MDIG trial and present follow-up study were registered prospectively at www.clinicaltrials.gov as NCT01924013 and NCT03537443, respectively. [ABSTRACT FROM AUTHOR]

Pancreatico-biliary (P-B) tumors arise from the pancreas, bile duct, and ampulla of Vater. Despite their close anatomical location, they have different etiology and biology. However, they uniformly share a poor prognosis, with no major improvements observed in overall survival over decades, even in the face of progress in diagnostic imaging and surgical techniques, and advances in systemic and loco-regional radiation therapies. To date, cytotoxic treatment has been associated with modest benefits in the advanced disease setting, and survival for patients with stage IV disease has not exceeded a year. Therefore, there is a pressing need to identify better treatments which may impact more significantly. Frequently, encouraging signals of potential efficacy for novel agents in early phase clinical trials have been followed by disappointing failures in larger phase III trials, raising the valid question of how drug development can be optimized for patients with pancreatic adenocarcinoma and biliary tract malignancies. In this article we summarize the current therapeutic options for these patients and their limitations. The biological context of these cancers is reviewed, highlighting features that may make them resistant to standard chemotherapeutics and could be potential therapeutic targets. We discuss the role of early phase clinical trials, defined as phase I and non-randomised phase II trials, within the clinical context and current therapeutic landscape of P-B tumors and postulate how translational studies and trial design may enable better realization of emerging targets together with a proposed model for future patient management. A detailed summary of current phase I clinical trials in P-B tumors is provided. [ABSTRACT FROM AUTHOR]

Objective: To compare aortic intima media thickness (aIMT) to carotid intima media thickness (cIMT) as a marker of early atherosclerosis in children with type 1 diabetes mellitus and to examine the associations of aIMT to known cardiovascular risk factors. Study design: 66 children with type 1 diabetes mellitus (age, 14.1 ± 2.5 years; 37 male) and 32 healthy control subjects (age, 14.2 ± 3 years; 15 male) underwent assessment of vascular structure (cIMT and aIMT) and vascular function (flow mediated dilatation [FMD] and glyceryl trinitrate induced dilatation [GTN]). Fasting blood tests were taken to measure levels of hemoglobin A1c, high sensitive C reactive protein, total homocyst(e)ine, serum folate, red cell folate, and lipids. Results: aIMT, but not cIMT, was significantly greater in the children with type 1 diabetes mellitus than in control subjects (P < .001). In children with type 1 diabetes mellitus, aIMT correlated with glycosylated hemoglobin (r = 0.31, P = .01) and was independently associated with age (β = 0.38, P = .001) and low-density lipoprotein cholesterol level (β = 0.38, P = .001). Vascular function (GTN) was worse in children with type 1 diabetes mellitus who had an aIMT >95th percentile, as defined with the control subjects. Conclusions: aIMT is an earlier marker than cIMT of preclinical atherosclerosis in children with type 1 diabetes mellitus and relates to known cardiovascular risk factors and metabolic control. [Copyright &y& Elsevier]

Abstract: The behaviour of konjac glucomannan (KGM) and the galactomannans locust bean gum (LBG), guar gum and fenugreek gum at a concentration of 0.2wt% in mixtures with type B gelatin in the solution state at 40°C was examined by visual inspection. At gelatin concentrations of ∼2wt% and above, the mixtures with LBG and guar gum formed cloud-like flocs, attributed to association of unsubstituted “smooth” regions of the mannan backbone in response to segregative interactions with gelatin. Fenugreek gum, which has no such smooth regions, did not form flocs, but gave a dispersion of small, gel-like particles. Mixtures of gelatin with KGM showed the unusual, striking phenomenon of forming a single gel-like lump which remained suspended in the surrounding liquid, neither rising nor sinking. The single lumps formed by mixtures of 0.2wt% KGM with 5.0wt% gelatin were studied in detail. The gelatin content, as determined by macro-Kjedahl analysis and comparison of the area of differential scanning calorimetry (DSC) cooling and heating peaks with calibration curves for gelatin alone, was ∼1.35wt%. Rheological characterisation by low-amplitude oscillatory measurements and creep-recovery experiments showed that, despite its gel-like appearance, the lump had the properties typical of a solution of densely entangled polysaccharide coils, including close Cox–Merz superposition of steady-shear viscosity (η) and complex dynamic viscosity (η*). The concentration of KGM, determined by comparison of the maximum value of η* in the Newtonian region at low frequency with calibration curves for KGM alone, was 3.4wt%. The composition of the surrounding liquid was obtained by calculations of mass balance, giving values of 5.20wt% gelatin and 0.024wt% KGM. The “p-factor” determined as the ratio of water to gelatin in the solution divided by the ratio of water to KGM in the lump was 0.65, well within the range found for other biopolymer mixtures. It is concluded that the gelatin–KGM mixtures show normal liquid–liquid phase separation, but that the phases have exactly the same density, preventing resolution into two liquid layers, and that enthalpically unfavourable interactions are instead minimised by one of the phases assuming spherical geometry. [Copyright &y& Elsevier]

Abstract: Previous studies have shown that conformationally disordered, soluble biopolymers cause large enhancements in self-association of calcium pectinate, thermally denatured whey protein and gelling maltodextrin under conditions where the pre-gel solutions remained as a single phase. The purpose of the present work was to screen for similar enhancements in gel strength and rate of conformational ordering of gelatin on incorporation of soluble, disordered polysaccharides. Type B gelatin was used at a fixed concentration of 5.0wt%, at a pH well above its isoelectric point of ∼4.5. Mixtures were prepared at 45°C, where the gelatin is in the disordered coil form. Gel strength was characterised as Young''s modulus (E), derived from the initial slope of compression curves for gels formed by holding for 16h at 5°C. Rate of conformational ordering of gelatin (triple-helix formation) was monitored by changes in optical rotation during and after rapid quenching from 45 to 5°C. The polysaccharides studied were carboxymethylcellulose (CMC), hydroxypropylmethylcellulose (HPMC), guar gum, gum arabic, dextran and inulin, all of which were used in compression testing. Combinations of gelatin with HPMC and guar gum became immediately turbid on mixing and could not, therefore, be included in the samples characterised by optical rotation. The other mixtures remained homogeneous (i.e. single-phase) on holding at 45°C. The results obtained were entirely negative. Incorporation of the soluble polysaccharides caused no significant changes in Young''s modulus, and optical rotation values remained within ∼10% of those for gelatin alone. It is suggested that the enthalpic advantage of segregation is sufficient to overcome the small reduction in entropy from association of conformationally immobile subunits in gelation of calcium pectinate, whey protein and maltodextrin, but not sufficient to overcome the much greater loss of entropy from conversion of flexible gelatin coils to rigid triple helices. [Copyright &y& Elsevier]

Abstract: Background: Preliminary efforts to demonstrate the utility of a self-rated version of the Yale-Brown Obsessive–Compulsive Scale (Y-BOCS) have been promising; however, earlier reports are based on small clinical samples. The objective of the present study was to evaluate the level of agreement between the clinician-administered Y-BOCS and a self-report version. Methods: Participants included 86 individuals with a principal diagnosis of obsessive–compulsive disorder (OCD). All participants were given the self-report version of the Y-BOCS to complete offsite and instructed to return it at a second assessment session (within a 2-week time frame), at which time a trained and experienced clinician administered the Y-BOCS interview. Results: The two versions were moderately correlated with the highest correlation observed for the Compulsions subscale. Comparison of scores for individual items revealed several inconsistencies between the two measures: level of agreement was low for resistance items, and the interview version generated higher compulsion severity ratings. Conclusions: The study provided moderate support for the convergence of the self-report and clinician-administered version of the Y-BOCS, however, important difference were detected between the two assessment methods. [ABSTRACT FROM AUTHOR]

In a qualitative interview study of 77 families with stored frozen embryos, we found that while embryo disposition decision making was influenced by individual life circumstances, embryo quantity/quality, personal values, embryo conceptualization, and clinic information, it was a stepwise process that could be represented as three sequential questions: (1) Will the embryos be used for additional attempts at conception? If not, (2) Will the embryos remain in storage? And if not, (3) Will the embryos be donated to other people or to science, or will they be destroyed? While almost two-thirds (63%) of participants kept their embryos in storage after 5 years, either passively through disagreement or indecision or actively to maintain embryo potential, avert feelings of loss, or as psychological or genetic “insurance,” IVF clinic support and detailed information about options motivated families to make disposition decisions. [Copyright &y& Elsevier]

Objective: To describe frozen embryo holders' expectations and perceptions of IVF clinic information, support, and storage fees and their relevance to embryo disposition decision making.Design: Qualitative interview study.Setting: Three northern California IVF practices.Patient(s): One hundred six families (110 women and 74 men) with an average of six frozen embryos in storage for 5 years.Intervention(s): Three in-depth interviews over 1 year.Main Outcome Measure(s): Thematic analysis of interview transcripts.Result(s): Although embryo holders expected that IVF clinics were under obligation to assist in the disposition decision and would be their main source of information, these expectations did not become manifest until years after embryo cryopreservation. Patients expressed a variety of preferences for the timing, format, and content of information and support, ranging from detailed written information to counselor/advocates that could provide logistical guidance and/or psychologic support. Embryo holders perceived an insufficiently defined infrastructure to facilitate donation to other couples, whereas donating to medical research was seen as less complicated and more likely to be encouraged and supported by physicians and clinics. Although increasing storage fees motivated disposition decision making, they could be interpreted as coercive and/or not reflective of actual clinic costs.Conclusion(s): Frozen embryo-holding patients' expectations of information and support to assist them with disposition decision making and embryo donation suggests that IVF clinics may benefit from a review of their frozen embryo counseling, storage, and disposition policies and procedures. [ABSTRACT FROM AUTHOR]

Objective: To provide insight into the experience of low-income immigrant Latino couples seeking infertility treatment.Design: Qualitative interview study.Setting: Infertility clinic at a university-affiliated urban public teaching hospital.Patient(s): Infertile low-income immigrant Latino couples (105 women and 40 men).Intervention(s): In-depth, tape-recorded interviews.Main Outcome Measure(s): After transcription and translation, the interviews were coded and analyzed for thematic content.Result(s): Four major challenges to providing infertility services to this population were identified: [1] communication: language and cultural barriers resulted in patients having difficulty both in understanding diagnoses and treatments and in communicating their questions, concerns, and experiences to physicians; [2] continuity: because medical students and residents rotated frequently, patients usually saw a different physician at each visit; [3] bureaucracy: patients reported having difficulty with appointment scheduling, follow-up visits, and timed laboratory procedures; and [4] accessibility: patients faced issues of limited availability and affordability of treatment.Conclusion(s): At a large, urban, university-affiliated infertility clinic, challenges related to communication, comprehension, continuity, bureaucracy, accessibility, availability, and affordability impeded the delivery of optimal infertility care to many low-income immigrant Latino patients. A greater availability of translators and both patient and physician cultural orientations to address these health care barriers is recommended. [ABSTRACT FROM AUTHOR]