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BackgroundDiabetes is associated with premature morbidity and mortality from its many complications. There are limited data on the chronic complications of diabetes in children and adolescents in sub-Saharan Africa. ObjectiveThe study aims to determine the (1) burden and related factors of chronic systemic complications of diabetes, including diabetic and nondiabetic ocular conditions in children and adolescents, and (2) quality of life (QoL) of participants compared to healthy controls. This manuscript describes the study methodology. MethodsDemographic information, medical history, anthropometric measurements, and laboratory characteristics were collected, and the participants were screened for microvascular and macrovascular complications as well as nondiabetic ocular disease. QoL questionnaires were administered to participants, their caregivers, and controls. Participants were followed up annually up to 3 years to determine the natural history of and trends in these conditions. SPSS Version 25.0 will be used for data analysis. Continuous and categorical data will be presented as mean (SD) and as percentages (%), respectively. t tests and analysis of variance will be used to compare means, and chi-square tests will be used to compare categorical data. Correlation, regression, and logistic regression analyses will be employed to establish linear associations and causal associations as appropriate. Relative risk and odds ratios will be used to estimate risk. QoL outcomes in Ghanaian children and adolescents with diabetes mellitus compared with caregivers and healthy controls will be assessed using the Pediatric Quality of Life inventory. Significance will be set at α=.05. ResultsInstitutional approval from the Ethical and Protocol Review Committee of the University of Ghana Medical School was received on August 22, 2014 (Protocol Identification Number: MS-Et/M.12-P4.5/2013-2014). Funding for the project was received from the University of Ghana Research Fund (#UGRF/9/LMG-013/2015-2016) in March 2016. Patient recruitment, clinical examination, and data collection commenced in August 2016 and was completed in September 2019. A total of 58 children and adolescents with diabetes mellitus have been recruited. Blood samples were stored at –80 °C for analysis, which was completed at the end of July 2020. Data analysis is ongoing and will be completed by the end of December 2020. Investigators plan to submit the results for publication by the end of February 2021. ConclusionsThe prevalence, natural history, trends in diabetic complications and nondiabetic ocular disease, and QoL will be provided. Our data may inform policies and interventions to improve care given to children and adolescents with diabetes. International Registered Report Identifier (IRRID)DERR1-10.2196/21440

Background: Type 1 diabetes (T1D) management exerts a considerable financial burden on patients, caregivers, and developing nations at large. In Ghana, a key governments effort to attenuate the financial burden of T1D on patients was to fashion safety-net mechanisms through financial risk pooling/sharing known as the National Health Insurance Scheme (NHIS). However, there is limited research on patients and caregivers' experiences with the cost of managing T1D within the NHIS in Ghana., Objective: This study explored the cost of T1D management, and the impact of the NHIS policy on mitigating costs of care., Methods: A semi-structured interview guide was developed to collect qualitative data from 28 young people living with T1D (PLWD), 12 caregivers, 6 healthcare providers, and other stakeholders in Western, Central and the Greater Accra regions. Multiple data collection techniques including mystery client and in-depth interviews were used to collect data. Thematic content analysis was performed with QSR NVivo 14., Results: Five key domains/themes which are: cost of T1D management supplies; cost of clinical care; cost of transportation; cost of diet; and NHIS were identified. The daily cost of blood glucose testing and insulin injection per day was between GHC 5-7 (US$ 0.6 to 1.0). The NHIS did not cover supplies such as strips, glucometers, HbA1c tests, and periodic medical tests. Even for those cost which were covered by the NHIS (mainly pre-mixed insulin), marked government delays in funds reimbursement to accredited NHIS facilities compelled providers to push the financial obligation onto patients and caregivers. Such cost obligations were fulfilled through out-of-pocket top-up or full payment of insulin of about GHC 15-25 (US$ 2-4), and GHC 25-50 (US$4-8) depending on the region and place of residence., Conclusion: The cost of managing T1D was a burden for patients and their caregivers. There was a commodification of life-saving insulin on the Ghanaian market, and the NHIS did not function well to ease the cost-burden of T1D management on patients and caregivers. The findings call for the need to scale up NHIS services to include simple supplies, particularly test strips, and always ensure the availability of life-saving insulin in healthcare facilities., (© 2024. The Author(s).)

Objectives: To investigate the prevalence of macrovascular and non-ocular microvascular complications and the associated factors among children and adolescents with diabetes mellitus in selected hospitals in southern Ghana., Design: A cross-sectional study., Setting: The out-patient clinics of the Departments of Child Health, Medicine and Therapeutics, Family Medicine, Ophthalmology, and the National Diabetes Management and Research Centre, all at the Korle Bu Teaching Hospital, Accra, as well as from Cape-Coast Teaching Hospital in the Central Region of Ghana., Participants: Fifty-eight children and adolescents aged 4-19 years who had been diagnosed with diabetes mellitus., Main Outcome Measures: Macrovascular (peripheral artery disease and coronary heart disease) and non-ocular microvascular complications (neuropathy and nephropathy)., Results: Data from 58 children and adolescents with diabetes were analysed. The mean age of participants was 14.6±2.6 years, and a female preponderance was observed (45, 77.6%). The prevalence of macrovascular and non-ocular microvascular complications was 27.6% and 8.6%, respectively. Long duration of diabetes diagnosis (p=0.044) and low triglycerides (p=0.009) were associated with microvascular complications, while high triglycerides (p=0.032), lower HDL cholesterol (p=0.046), and abnormal body mass index (p=0.020) were associated with macrovascular complications., Conclusions: Macrovascular and non-ocular microvascular complications are common among children and adolescents with diabetes in southern Ghana and are associated with a long duration of diabetes diagnosis, abnormal body mass index, low HDL cholesterol, and triglyceride levels. Therefore, the early institution of regular screening for diabetes-related complications to allow early detection and appropriate management is recommended., Funding: University of Ghana Research Fund., Competing Interests: Conflict of interest: None declared, (Copyright © The Author(s).)

Background: Despite the fact that the rate of type 1 diabetes (T1D) is increasing worldwide, there exists a dearth of information on the disease in most sub-Saharan African countries. The goal of this study was to determine the enrolment trend of T1D using data compiled over 28 y from a teaching hospital in Kumasi, Ghana., Methods: Information collected included sex, age at diagnosis and date of T1D diagnosis. We identified trends from 1992 to 2018, divided into 3 y intervals., Results: From 1992 to 2018, 1717 individuals with T1D were enrolled in the diabetes clinic at the Komfo Anokye Teaching Hospital. The male:female ratio was 1:1.2. The number of individuals diagnosed with T1D decreased among the 10-19 y age group during the 1992-1994 period, followed by a progressive increase within the same age group during the subsequent period (from 35.4% in 1995-1997 to 63.2% in 2016-2018). There was a decline in the proportion of children 0-9 y of age diagnosed during the study period (from 5.1% in 1992-1994 to 3.6% in 2016-2018)., Conclusions: In our study population, a decreasing trend of T1D enrolments was observed in general while among adolescents an increasing trend was observed., (© The Author(s) 2020. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: The main objective of the study was to determine the prevalence of diabetic retinopathy (DR), other diabetes-related ocular changes (e.g., cataracts, corneal ulceration), and non-diabetic ocular disease in Ghanaian children and adolescents. The second objective was to evaluate the relationship between these conditions and age at diagnosis, current age, diabetes mellitus (DM) duration, and participant's sex., Methods: A cross-sectional study, undertaken by a multidisciplinary team, included a cohort of children and adolescents (4-19 years) with DM recruited from selected health facilities in Ghana, from March 2016 to September 2019, after written informed consent or assent. The cohort will be followed up for 3 years to determine the natural course of the ocular changes, reported later. Participants were examined for all microvascular and macrovascular complications, non-diabetic ocular disease, anthropometric measurements, laboratory characteristics and quality of life issues. Full ocular examination was also undertaken. Statistical Package for Social Sciences (SPSS Version 25.0) was used for the data analysis. Continuous and categorical variables were presented as mean and standard deviation (SD), median (interquartile range) and as percentages (%), respectively. T-test and Mann-Whitney U test were used in establishing associations., Results: A total of 58 participants were recruited. DR was detected in only 1 out of 58 (1.7%) participants at baseline. Cataracts were the most common ocular finding, detected in 42 (72%) at baseline. Other anterior segment changes observed included blepharitis 46 (79.3%) and tear film instability 38 (65.5%). There was a significant positive association between duration of the DM and the risk of cataract ( p = 0.027). Participants' age at diagnosis was significantly associated with the presence of prominent corneal nerves ( p = 0.004)., Conclusions: DR was uncommon in this cohort of young persons with DM in Ghana. Cataracts, blepharitis and refractive errors were ocular changes commonly observed. All young persons with diabetes should undergo regular eye examination in all clinics where follow-up care is provided.

Background: Endocrine disorders have been noted to be on the increase in the developing world, but little is known about their outcomes on the African continent., Methods: We conducted a retrospective longitudinal study to evaluate the demographic characteristics and determinants of endocrine-related mortality among adult patients over 9 y in a leading tertiary hospital in Ghana. We determined the predictors of inpatient mortality using Kaplan-Meier survival curves and Cox proportional hazard regression analysis., Results: Overall, 6265 patients (9.7% of all medical admissions) were admitted with various endocrine disorders during the period. The most common endocrine cause of hospitalisation was diabetes mellitus (86.0%), followed in order of decreasing frequency by thyroid disorders (7.7%) and miscellaneous disorders (1.4%). The overall crude mortality rate of endocrine admissions was 16.7%. Death was predicted by increasing age with an adjusted hazard ratio of 1.25 (95% confidence interval 1.15 to 1.65) for every 10-y increase in age., Conclusions: Almost one in six adults admitted with an endocrine disorder to a tertiary care centre in Ghana died in hospital, and many of the deaths were due to non-communicable disease complications. Enhanced public health disease prevention strategies and endocrine inpatient care processes are warranted., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives : Aquaculture encompasses a variety of species in both freshwater and marine settings and can combine elements of agriculture and fishing, two recognized hazardous occupations. Efforts are underway to expand the aquaculture sector in the United States (U.S.), and should be informed by occupational safety and health (OSH) research. The objectives of this review paper are to: i) describe the U.S. aquaculture sector, ii) summarize statistics, peer-reviewed studies, and reports focused on U.S. aquaculture OSH, and iii) describe the policy landscape specific to U.S. aquaculture OSH. Methods : Literature searches employed databases and Internet search engines to identify relevant peer-reviewed articles, reports, and other resources. Due to the expected U.S. expansion of marine aquaculture and paucity of peer-reviewed U.S.-based OSH literature in this sector, additional searches for international research on marine aquaculture were conducted. Results : The U.S. Bureau of Labor Statistics estimated high rates of illness and injury among U.S. aquaculture workers in 2014 and 2015. Peer-reviewed literature on aquaculture OSH identified numerous physical, chemical, and biological OSH risks depending on production methods and settings. Significant policy gaps exist regarding U.S. aquaculture OSH surveillance, reporting, and regulation. Conclusion : This review identifies a critical need for research, surveillance, and best practices information, specific to the major types of aquaculture in the U.S., to augment and inform worker safety and health efforts in this expanding sector.

Background: Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from "at-risk" to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from "at-risk" to RA., Methods: We performed global profiling of 754 miRNAs per patient on a matched serum sample cohort of 12 anti-cyclic citrullinated peptide (CCP) + "at-risk" individuals that progressed to RA. Each individual had a serum sample from baseline and at time of detection of synovitis, forming the matched element. Healthy controls were also studied. miRNAs with a fold difference/fold change of four in expression level met our primary criterion for selection as candidate miRNAs. Validation of the miRNAs of interest was conducted using custom miRNA array cards on matched samples (baseline and follow up) in 24 CCP+ individuals; 12 RA progressors and 12 RA non-progressors., Results: We report on the first study to use matched serum samples and a comprehensive miRNA array approach to identify in particular, three miRNAs (miR-22, miR-486-3p, and miR-382) associated with progression from systemic autoimmunity to RA inflammation. MiR-22 demonstrated significant fold difference between progressors and non-progressors indicating a potential biomarker role for at-risk individuals., Conclusions: This first study using a cohort with matched serum samples provides important mechanistic insights in the transition from systemic autoimmunity to inflammatory disease for future investigation, and with further evaluation, might also serve as a predictive biomarker.

Human cytomegalovirus (CMV) induces the formation of effector CD8(+) T cells that are maintained for decades during the latent stage of infection. Effector CD8(+) T cells appear quiescent, but maintain constitutive cytolytic capacity and can immediately produce inflammatory cytokines such as IFN-γ after stimulation. It is unclear how effector CD8(+) T cells can be constitutively maintained in a terminal stage of effector differentiation in the absence of overt viral replication. We have recently described the zinc finger protein Homolog of Blimp-1 in T cells (Hobit) in murine NKT cells. Here, we show that human Hobit was uniformly expressed in effector-type CD8(+) T cells, but not in naive or in most memory CD8(+) T cells. Human CMV-specific but not influenza-specific CD8(+) T cells expressed high levels of Hobit. Consistent with the high homology between the DNA-binding Zinc Finger domains of Hobit and Blimp-1, Hobit displayed transcriptional activity at Blimp-1 target sites. Expression of Hobit strongly correlated with T-bet and IFN-γ expression within the CD8(+) T-cell population. Furthermore, Hobit was both necessary and sufficient for the production of IFN-γ. These data implicate Hobit as a novel transcriptional regulator in quiescent human effector-type CD8(+) T cells that regulates their immediate effector functions., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The reactions of the diaryl-diselenides (p-FC(6)H(4))(2)Se(2) and (p-ClC(6)H(4))(2)Se(2) with diiodine have been investigated. Species of stoichiometry "RSeI" are formed when the ratio employed is 1:1. The solid-state structure of "(p-FC(6)H(4))SeI" has been determined, and shown to be a charge-transfer (CT) adduct, (p-FC(6)H(4))(2)Se(2)I(2), where the Se-Se bond is retained and the diiodine molecule interacts with only one of the selenium atoms. The Se-I bond in (p-FC(6)H(4))(2)Se(2)I(2) is 2.9835(12) Å, which is typical for a (10-I-2) Se-I-I CT system. When diiodine is reacted in a 3:1 ratio with (p-XC(6)H(4))(2)Se(2) (X = F, Cl) species of stoichiometry "RSeI(3)" are formed. The structure of "(p-ClC(6)H(4))SeI(3)" reveals that this is not a selenium(IV) compound, but is better represented as a selenium(II) CT adduct, (p-ClC(6)H(4))SeI·I(2). The Se-I bond to the diiodine molecule is typical in magnitude for a CT adduct, Se-I: 2.8672(5) Å, whereas the other Se-I bond is much shorter, Se-I: 2.5590(6) Å, and is a genuine example of a rarely observed covalent Se-I bond, which appears to be stabilised by a weak Se···I interaction from a neighbouring iodine atom. The reaction of (p-ClC(6)H(4))SeI with Ph(3)P results in the formation of a CT adduct, Ph(3)PSe(p-ClC(6)H(4))I, which has a T-shaped geometry at selenium (10-Se-3). By contrast, the reaction of (p-FC(6)H(4))SeI with Ph(3)P does not form an adduct, but results in the formation of Ph(3)PI(2) and (p-FC(6)H(4))(2)Se(2).

A series of di(para-halophenyl)diselenides, (p-XC(6)H(4))(2)Se(2) (X = F, Cl) have been reacted with three equivalents of SO(2)Cl(2) or Br(2), leading to the formation of selenium(iv) RSeX(3) compounds. The structures of (p-FC(6)H(4))SeX(3) (X = Cl, Br) have been determined, and both exhibit a dimeric RSeX(2)(μ-X)(2)RSeX(2) structure consisting of two "saw-horse" (p-FC(6)H(4))SeX(3) units linked by two halide bridges, with an overall square pyramidal geometry at selenium. In both structures all the selenium and halogen atoms are planar, with both aryl rings located on the same side of the Se(2)X(6) plane (cis-isomer). The structure of (p-ClC(6)H(4))SeCl(3) also adopts a planar dimeric structure, however both cis- and trans-dimeric molecules are co-crystallised in the unit cell. In contrast, the structure of (p-ClC(6)H(4))SeBr(3) adopts a folded cis-dimeric structure due to steric constraints. Secondary Se···X interactions to the "vacant" sixth coordination site at selenium are a feature of most of these structures, but are most prominent in the folded structure of (p-ClC(6)H(4))SeBr(3). A re-examination of the PhSeBr/PhSeBr(3) system resulted in the isolation of crystals of a second structural form of "PhSeBr". The structure of Ph(2)Se(2)Br(2) consists of two PhSeBr units linked by an elongated Se-Se bond of 2.832(4) Å, and longer secondary Se···Br interactions of 3.333(4) Å to form a chain structure. Further weak Se···Br and Br···Br interactions are present, which form loosely linked rippled sheets of selenium and bromine atoms, similar to the sheets observed for the tetrameric form, Ph(4)Se(4)Br(4).

Plasma cells (PCs), the terminal effectors of humoral immunity, are short-lived unless supported by niche environments in which they may persist for years. No model system has linked B cell activation with niche function to allow the in vitro generation of long-lived PCs. Thus, the full trajectory of B cell terminal differentiation has yet to be investigated in vitro. In this article, we describe a robust model for the generation of polyclonal long-lived human PCs from peripheral blood B cells. After a proliferative plasmablast phase, PCs persist in the absence of cell division, with viability limited only by elective culture termination. Conservative predictions for PC life expectancy are 300 d, but with the potential for significantly longer life spans for some cells. These long-lived PCs are preferentially derived from memory B cells, and acquire a CD138(high) phenotype analogous to that of human bone marrow PCs. Analysis of gene expression across the system defines clusters of genes with related dynamics and linked functional characteristics. Importantly, genes in these differentiation clusters demonstrate a similar overall pattern of expression for in vitro and ex vivo PCs. In vitro PCs are fully reprogrammed to a secretory state and are adapted to their secretory load, maintaining IgG secretion of 120 pg/cell/day in the absence of XBP1 mRNA splicing. By establishing a set of conditions sufficient to allow the development and persistence of mature human PCs in vitro, to our knowledge, we provide the first platform with which to sequentially explore and manipulate each stage of human PC differentiation.

The reactions of the group 15 trihalides, MX(3) (M = As, Sb, Bi; X = Cl, Br), with the phosphine selenide SeP(p-FC(6)H(4))(3) result in the formation of co-crystals of formula MX(3)·SeP(p-FC(6)H(4))(3). No reaction was observed with MI(3) (M = As, Sb, Bi). The structures of MX(3)·SeP(p-FC(6)H(4))(3) (M = As, X = Br 2; M = Sb, X = Cl 3; M = Bi, X = Cl 5; M = Bi, X = Br 6) have been established, and are isomorphous, crystallising in the cubic I23 space group. All the structures feature a primary MX(3) unit, which has three weak secondary MSe interactions to SeP(p-FC(6)H(4))(3) molecules. However, each of these SeP(p-FC(6)H(4))(3) molecules bridges three MX(3) molecules, resulting in the generation of an M(4)Se(4) (M = As, Sb, Bi) distorted cuboid linked by the pnictogen-chalcogen interactions. Four opposing corners of the cuboid are occupied by the M atom (M = As, Sb, Bi) of an MX(3) pyramid, and the other four by the selenium atom of the phosphine selenide.

The group 15 ligands (o-CH(3)C(6)H(4))(3)P, (m-CH(3)C(6)H(4))(3)P, (p-CH(3)C(6)H(4))(3)P, Ph(3)As, (o-CH(3)C(6)H(4))(3)As and (p-CH(3)C(6)H(4))(3)As have been reacted with two equivalents of di-iodine or di-bromine to yield complexes of formula R(3)EX(4) (E = P, As; X = I, Br). These halogenated group 15 compounds are ionic, [R(3)EX][X(3)] consisting of halo-phosphonium or halo-arsonium cations and trihalide anions. These adducts exhibit structural isomerism and may exist either as simple 1:1 ion pairs, [R(3)EX][X(3)], isomer (A), which display a weak XX interaction between cation and anion, or as a 2:1 complex, which consists of a [{R(3)EX}(2)X(3)](+) cationic species made up of two [R(3)EX](+) cations interacting with one [X(3)](-) anion. The overall charge is balanced by a second [X(3)](-) anion. These 2:1 species also exhibit structural isomerism due to subtle differences in the connectivity of the [{R(3)EX}(2)X(3)](+) fragment, as the {R(3)EX}(+) units may either interact at the same end of the [X(3)](-) ion, to give a Y-shaped motif, isomer (B), or at opposite ends, giving a Z-shaped motif, isomer (C). The type of structural isomer formed is related to the way in which [Ar(3)EX](+) cations pack together via aryl embraces. Isomer (A) and (C) structures form chains of side-to-side, anti-parallel embracing cations. In (A) and (C) structures a square-like stacking motif of cations is observed. In contrast, isomer (B) structures feature side-to-side, parallel embracing cations, and do not exhibit the square motif.

During cellular differentiation, mRNA transcription and translation require precise coordination. The mechanisms controlling this are not well defined. IL-21 is an important regulator of plasma cell differentiation, and it controls the master regulator of plasma cell differentiation, B lymphocyte-induced maturation protein-1 (BLIMP-1), via STAT3 and IRF4. Among the other targets of STAT3 is microRNA-21 (miR-21). miR-21 is the most frequently deregulated microRNA in malignancy, including B cell lymphomas, and it has oncogenic potential downstream of STAT3. However, the regulation and function of miR-21 during plasma cell differentiation are not characterized. In contrast to the induction of miR-21 observed in response to STAT3 activation in other systems, we demonstrate that miR-21 is repressed during IL-21-driven plasma cell differentiation. We explored the molecular basis for this repression and identify primary miR-21 transcription as a direct target of BLIMP-1-dependent repression, despite continued STAT3 activation and phospho-STAT3 binding to the primary miR-21 promoter. Thus, STAT3 and BLIMP-1 constitute an incoherent feed-forward loop downstream of IL-21 that can coordinate microRNA with mRNA expression during plasma cell differentiation.

In the title compound, C(36)H(25)F(6)O(2)P(2)(+)·I(3)(-), hydrogen-bonded [{(p-FC(6)H(4))(3)PO}(2)H](+) dimers assemble along the crystallographic c axis to form channels that house extended chains of triiodide anions. Although the I-I bond lengths of 2.9452 (14) and 2.9023 (15) Å are typical, the inter-ion I...I distance of 3.5774 (10) Å is unusually short. A posteriori modelling of nonmerohedral twinning about (100) has been only partially successful, achieving a reduction in the maximum residual electron density from 5.28 to 3.24 e Å(-3). The inclusion of two low-occupancy I-atom sites (total 1.7%), which can be interpreted as translational disorder of the triiodide anions along the channels, reduced the maximum residual electron density to 2.03 e Å(-3). The minor fractional contribution volume of the nonmerohedral twin domains refined to 0.24 and simultaneous refinement of the inversion twin domains showed the crystal to be a 0.5:0.5 inversion twin.

A series of gold(I) phosphine complexes of the type [AuCl{PR(2)(R(f))}] (R = Et, i-Pr, Cy; R(f) = CF = CF(2); R = Ph, R(f) = C = CFH, CCl = CF(2), C ≡ CCF(3), CF(3), i-C(3)F(7), s-C(4)F(9)) have been prepared and most have been structurally characterised. All of the complexes are monomeric in the solid state, and a number of secondary interactions are observed--including short intramolecular AuF distances, metal-bound Au-ClH non-classical hydrogen bonds, fluorous domains and phenyl embraces. Only in the case of [AuCl{PEt(2)(CF = CF(2))}] is an aurophilic interaction with an AuAu contact less than the sum of the van der Waals radii observed. Even then, the distance, 3.3458(10) Å, is longer than that previously observed for the related complex with R = Ph; R(f) = CF = CF(2).

Catabolism of tryptophan by IDO1 plays an important role in the control of immune responses. Activation of the eukaryotic initiation factor 2alpha (eIF2alpha) kinase general control nonderepressible-2 (GCN2) following tryptophan depletion is a major pathway mediating this effect. However, immunomodulatory target genes of GCN2 activation are poorly defined. The transcriptional repressor B lymphocyte-induced maturation protein-1 (BLIMP-1) is a target of the eIF2alpha kinase1, protein kinase-like ER kinase (PERK) during the unfolded protein response of the endoplasmic reticulum. Thus, BLIMP-1 might also be a mediator of the GCN2 stress response pathway activated by IDO1 and tryptophan depletion. Indeed, in human monocytes BLIMP-1 mRNA and protein are up-regulated in response to both a pharmacological activator of GCN2 and tryptophan-depletion generated by IDO1-transfected cells. This suggests a functional role for BLIMP-1 in the immunomodulatory effects of the IDO1-GCN2 axis. BLIMP-1 has been shown to repress IFN-gamma-regulated promoters. As IDO1 is itself highly responsive to IFN-gamma, we hypothesized that BLIMP-1 functions in a feedback loop to regulate IDO1 expression. We found that BLIMP-1 binds to IFN-responsive sites in the IDO1 promoter and represses IFN-dependent IDO1 activation. We propose that BLIMP-1 acts in a negative feedback loop to successfully balance the outcome of tolerance vs inflammation.

The reactions of the tris-dialkylamino phosphines (Et2N)3P and (nPr2N)3P, and the pyrrolidinyl substituted phosphines (C4H8N)3P and tBuP(NC4H8)2, with I2 and (Ph2Se2I2)2, have been reported. The reactions with diiodine lead to the formation of [R3PI]I adducts, which are essentially ionic, but show a tendency to display long, soft-soft, II interactions in the solid state. The crystal structures of [(Et2N)3PI]I, (1), [(nPr2N)3PI]I, (2), and [(C4H8N)3PI]I, (3), have all been determined, and display II interactions varying between 3.5170(6) and 3.6389(14) A. The analogous reactions with (Ph2Se2I2)2 lead to the formation of phenylseleno-phosphonium salts, [R3PSePh]I. The structures of [(C4H8N)3PSePh]I, (6) and [(C4H8N)2tBuPSePh] I, (7), have been determined and do not display any soft-soft interactions between the selenium and iodine atoms. All of the phosphonium salts represent examples of structures containing tris-dialkylamino phosphine fragments which show no special nitrogen atom, i.e. all three nitrogen atoms are planar. This type of arrangement is usually observed when a C3 symmetric conformation is observed, (which is the case for 1 and 2), but not for the (C4H8N)3P adducts 3 and 6, where the conformation is closer to Cs, although the nitrogen atoms are still essentially planar. The P-N bonds in all the compounds reported herein are short, ranging between 1.599(12) A and 1.643(12) A, and are consistent with the previously reported short P-N bonds in phosphonium salts featuring tris-dialkylamino substituted phosphines.

The coordination chemistry of the perfluorovinyl phosphines PEt2(CF=CF2), P(i)Pr2(CF=CF2), PCy,(CF=CF2) and PPh(CF=CF2)2 to rhodium(I), palladium(II), and platinum(II) centres has been investigated. The electronic properties of the ligands are estimated based on v(CO) and 1J(Rh-P) values. X-Ray diffraction data for the square-planar Pd(II) and Pt(II) perfluorovinyl-phosphine containing complexes allow estimates of the steric demand for the series of ligands PPh2(CF=CF2), PEt2(CF=CF2), P(i)Pr2(CF=CF2), PCy2(CF=CF2) and PPh(CF=CF2)2 to be determined. The (CF=CF2) fragment is found to be more electron withdrawing than (C6F5) yet sterically less demanding. These ligands therefore provide a range of electron-neutral to phosphite-like electronic properties combined with a range of steric demands. This study also reveals that short intramolecular interactions from the metal centre to the beta-fluorine atom cis to phosphorus of the CF=CF2 groups are observed in all-trans square planar complexes of the ligands. Unusually, the complex [PtCl2{P(i)Pr2(CF=CF2)}2] crystallises with both cis- and trans-isomers present in the unit cell. It appears that co-crystallisation of both isomers occurs in order to maximise fluorous regions in the crystal packing, and the extended structure displays short fluorine-fluorine contacts. The generation of mixed geometries seems to be a phenomenon of crystallisation, as solution phase NMR studies reveal the presence of only the trans-isomer.

Tris-(dimethylamino)phosphine reacts with I(2) to form (Me(2)N)(3)PI(2), which when recrystallised from acetonitrile displays a structure of overall stoichiometry [{(Me(2)N)(3)PI}I](6).CH(3)CN . The asymmetric unit of consists of four different [(Me(2)N)(3)PI](+) cations, one of these exhibits a cation-anion interaction to an iodide ion, with an I-I contact distance of 3.6378(14) A, the longest yet observed for an R(3)PI(2) compound. Two of the other three cations display no interactions, whilst a cation-solvent interaction is observed for the fourth. When (Me(2)N)(3)PI(2) is recrystallised from dichloromethane the molecule abstracts chlorine from the solvent to form [(Me(2)N)(3)PCl]I this latter compound can also be synthesised directly from (Me(2)N)(3)P and ICl. The reaction of (Me(2)N)(3)P with IBr forms [(Me(2)N)(3)PBr]I, which when recrystallised from chlorinated solvents forms [(Me(2)N)(3)PCl(0.5)Br(0.5)]I. The analogous [(Me(2)N)(3)PCN]I, does not display CN-Cl exchange and can be recrystallised from dichloromethane. The structures of and have all been determined by X-ray diffraction. All of the (Me(2)N)(3)P groups in the cations in, and exhibit a C(3) conformation, in contrast to the majority of (R(2)N)(3)P systems where a C(s) conformation is usually preferred. This C(3) conformation appears to be favoured where there is increased positive charge on phosphorus, as is the case in the phosphorus(v) ionic species described herein. This conformation allows greater P-N pi-bonding, and as a result the P-N bonds are shortened, varying between 1.566(10) and 1.624(10) A in these compounds.

The reaction of (Ph(2)Se(2)I(2))(2) with a wide variety of tertiary phosphines possessing different steric and electronic properties has been studied, leading in most cases to R(3)PSe(Ph)I adducts; [R(3)P = (p-CH(3)C(6)H(4))(3)P (1), (m-CH(3)C(6)H(4))(3)P (2), (o-OCH(3)C(6)H(4))(3)P (4), Ph(2)MeP (6), Me(2)PhP (7), Me(3)P (8), Cy(3)P (9)]. All of the products formed were characterised by elemental analysis, Raman and multinuclear NMR spectroscopy. Both steric and electronic factors are important in determining the structural motif (CT vs. ionic) observed in the solid-state. In general, highly basic phosphines result in a lengthening of the Se-I interaction, and a preference for an ionic structure. The reaction with (o-CH(3)C(6)H(4))(3)P does not yield a stable R(3)PSe(Ph)I adduct, and instead (o-CH(3)C(6)H(4))(3)PI(2) (3) is formed. The unusually long P-I bond, [2.5523(12) A], and short I-I bond, [3.0724(4) A], exhibited by is a result of the high steric requirements of this phosphine. The similarly bulky (o-SCH(3)C(6)H(4))(3)P yields a mixture of (o-SCH(3)C(6)H(4))(3)PSe(Ph)I (5a) and [(o-SCH(3)C(6)H(4))(3)PSePh]I(3) (5b). The crystal structures of (m-CH(3)C(6)H(4))(3)PSe(Ph)I, 2, (o-CH(3)C(6)H(4))(3)PI(2), 3, [(o-OCH(3)C(6)H(4))(3)PSePh]I.CH(2)Cl(2), 4, [(o-SCH(3)C(6)H(4))(3)PSePh]I(3), 5b, two pseudo-polymorphs of Ph(2)MePSe(Ph)I, 6a/6b, and [Me(3)PSe(Ph)I](2).CH(2)Cl(2), 8, are reported. The R(3)PSe(Ph)I adducts formed exhibit one of four types of behaviour. Type I products, (such as 2) are CT in the solid-state and display fluxionality in solution. Type II products (such as 6a/6b) lie close to the CT/ionic structural borderline, displaying long Se-I bonds, and are more appropriately classified as [R(3)PSePh] (acceptor)/I(-) (donor) CT complexes. Type II complexes ionise in solution to [R(3)PSePh]I. Type III products, such as 8, are ionic in solution, but frequently show cation-anion, or cation-solvent interactions in the solid-state, although these interactions are weak and the linear P-Se-I motif is lost. Type IV products (such as 4) are ionic and feature bulky phosphines. They display no short cation-anion interactions in the solid-state.

The synthesis and characterisation of Ph(4)Se(4)Br(4) (1) directly from the reaction of Ph(2)Se(2) with dibromine is reported. The solid-state structure of 1 consists of four PhSeBr units linked by weak selenium-selenium bonds [3.004(2)-3.051(2) A] into a Se(4) square, and is structurally analogous to the previously reported Ph(4)Te(4)I(4). The reactions of Ph(4)Se(4)Br(4) with a variety of tertiary phosphines have been undertaken, resulting in the formation of compounds of formula R(3)PSe(Ph)Br. X-Ray crystallographic analysis of three of the compounds reveals different structural isomers. Ph(3)PSe(Ph)Br (2) is a charge-transfer (CT) compound [Se-Br 3.0020(8) A], with an essentially linear P-Se-Br bond angle, 172.15(4) degrees and T-shaped geometry at selenium. Me(3)PSe(Ph)Br (5) also contains the selenium atom in a T-shaped geometry, consistent with a CT formulation, although the Se-Br distance of 3.327(3) A is considerably longer than observed for 2. In contrast, Cy(3)PSe(Ph)Br (6) is an ionic phosphonium salt, [Cy(3)PSePh]Br with no short Se-Br interactions. Geometry at selenium is bent, as expected for an ionic compound. These results are discussed with reference to the previously reported iodo-compounds Ph(3)PSe(Ph)I and [(Me(2)N)(3)PSe(Ph)]I.

The crystal structures of PhSeX3(X=Cl, Br,) and their spectroscopic data are reported, with the structure of PhSeBr3 exhibiting interesting molecular, charge transfer, and ionic bonding aspects.

Bronchopulmonary foregut malformations (BPFM) are a heterogeneous group of pulmonary developmental anomalies that present at varying ages and with overlapping symptoms, signs and radiology. This article discusses the embryology of these lesions with reference to possible common origins and the link between aetiology and radiological appearance. The radiology of each lesion, both antenatally and postnatally, is described and illustrated. A number of quandaries exist in the prediction of prognosis and subsequent treatment of BPFM. We discuss the radiological features that may help to elucidate an individual prognosis and aid in the planning of treatment. The treatment options available for BPFM are briefly discussed. Finally, the link between BPFM, in particular cystic adenomatoid malformations and malignancy, is discussed. We aim to provide a comprehensive overview of the embryology, radiology, prognosis and treatment highlighting contentious issues of BPFM.

Objective: To investigate adherence to antiretroviral therapy and use of alternative therapies among older human immunodeficiency virus (HIV)-infected adults, and to assess relationships between antiretroviral adherence and clinical outcomes., Methods: One hundred older HIV-infected patients, aged 50 and over, treated at two large HIV clinics in Washington, DC, were enrolled. A cross-sectional methodology used structured interviews to investigate antiretroviral regimens, use of alternative therapies, and demographics. Medical records provided viral load and CD4 count within 3 months of interview., Results: The mean self-reported adherence was 94%, and 55 patients reported 100% adherence to antiretroviral therapy. Correlation analysis showed a significant negative correlation between adherence and viral load (r = -312, p = 0.005). There was no significant difference in adherence based on race, gender, mode of transmission, or education. Twenty-one patients (21%) reported the use of an alternative therapy, with several patients using multiple alternative therapies. There was no significant difference in adherence score (p = 0.514) or viral load (p = 0.860) based upon use of alternative therapies., Conclusions: Older HIV-infected study patients reported high levels of adherence to antiretroviral regimens, and adherence was highly correlated with HIV viral load. Use of alternative therapies did not significantly impact adherence to antiretroviral agents or viral load. High adherence among this older population may be related to older patients' familiarity with medication usage, their increasing awareness of HIV as a disease that requires optimal adherence, and educational efforts promoted by the two clinics in which they are clients.

A survey in Kansas compared the prevalence of gastrointestinal helminths and protozoa in 2 raccoon (Procyon lotor) populations; a population in a typical rural setting and a relatively undisturbed population on a military reservation. Gastrointestinal tracts of 128 raccoons were examined. Freeze storage of alimentary tracts prevented collection of data on trematode prevalence. Helminth infections other than trematodes included 1 acanthocephalan, 2 cestodes, and 3 nematodes. Helminths were found in all raccoons from the population on the military installation and 96% of those from the rural population. Prevalence of helminths was generally greater in raccoons from the population living in the rural setting. Eimeria spp. and Sarcocystis sp. were also found, whereas Giardia spp. and Cryptosporidium parvum were not.