Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study.

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2.

The view of Hong Kong parents on secondary use of dried blood spots in newborn screening program.

BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.

Effectiveness of a childbirth massage programme for labour pain relief in nulliparous pregnant women at term: a randomised controlled trial.

INTRODUCTION: The effect of massage for pain relief during labour has been controversial. This study investigated the efficacy of a programme combining intrapartum massage, controlled breathing, and visualisation for non-pharmacological pain relief during labour. METHODS: This randomised controlled trial was conducted in two public hospitals in Hong Kong. Participants were healthy low-risk nulliparous Chinese women ≥18 years old whose partners were available to learn massage technique. Recruitment was performed at 32 to 36 weeks of gestation; women were randomised to attend a 2-hour childbirth massage class at 36 weeks of gestation or to receive usual care. The primary outcome variable was the intrapartum use of epidural analgesia or intramuscular pethidine injection. RESULTS: In total, 233 and 246 women were randomised to the massage and control groups, respectively. The use of epidural analgesia or pethidine did not differ between the massage and control groups (12.0% vs 15.9%; P=0.226). Linear-by-linear analysis demonstrated a trend whereby fewer women used strong pharmacological pain relief in the massage group, and a greater proportion of women had analgesic-free labour (29.2% vs 21.5%; P=0.041). Cervical dilatation at the time of pethidine/epidural analgesia request was significantly greater in the massage group (3.8 ± 1.7 cm vs 2.3 ± 1.0 cm; P<0.001). CONCLUSION: The use of a massage programme appeared to modulate pain perception in labouring women, such that fewer women requested epidural analgesia and a shift was observed towards the use of weaker pain relief modalities; in particular, more women in the massage group were analgesic-free during labour.

State-wide utilization and performance of traditional and cell-free DNA-based prenatal testing pathways: the Victorian Perinatal Record Linkage (PeRL) study.

OBJECTIVES: To perform individual record linkage of women undergoing screening with cell-free DNA (cfDNA), combined first-trimester screening (CFTS), second-trimester serum screening (STSS), and/or prenatal and postnatal cytogenetic testing with the aim to (1) obtain population-based estimates of utilization of prenatal screening and invasive diagnosis, (2) analyze the performance of different prenatal screening strategies, and (3) report the residual risk of any major chromosomal abnormality following a low-risk aneuploidy screening result. METHODS: This was a retrospective study of women residing in the state of Victoria, Australia, who underwent prenatal screening or invasive prenatal diagnosis in 2015. Patient-funded cfDNA referrals from multiple providers were merged with state-wide results for government-subsidized CFTS, STSS and invasive diagnostic procedures. Postnatal cytogenetic results from products of conception and infants up to 12 months of age were obtained to ascertain cases of false-negative screening results and atypical chromosomal abnormalities. Individual record linkage was performed using LinkageWizTM . RESULTS: During the study period, there were 79 140 births and 66 166 (83.6%) women underwent at least one form of aneuploidy screening. Linkage data were complete for 93.5% (n = 61 877) of women who underwent screening, and of these, 73.2% (n = 45 275) had CFTS alone, 20.2% (n = 12 486) had cfDNA alone; 5.3% (n = 3268) had STSS alone, 1.3% (n = 813) had both CFTS and cfDNA, and < 0.1% (n = 35) had both STSS and cfDNA. CFTS had a combined sensitivity for trisomies 21 (T21), 18 (T18) and 13 (T13) of 89.57% (95% CI, 82.64-93.93%) for a screen-positive rate (SPR) of 2.94%. There were 12 false-negative results in the CFTS pathway, comprising 10 cases of T21, one of T18 and one of T13. cfDNA had a combined sensitivity for T21, T18 and T13 of 100% (95% CI, 95.00-100%) for a SPR of 1.21%. When high-risk cfDNA results for any chromosome (including the sex chromosomes) and failed cfDNA tests were treated as screen positives, the SPR for cfDNA increased to 2.42%. The risk of any major chromosomal abnormality (including atypical abnormalities) detected on prenatal or postnatal diagnostic testing after a low-risk screening result was 1 in 1188 for CFTS (n = 37) and 1 in 762 for cfDNA (n = 16) (P = 0.13). The range of chromosomal abnormalities detected after a low-risk cfDNA result included pathogenic copy-number variants (n = 6), triploidy (n = 3), rare autosomal trisomies (n = 3) and monosomy X (n = 2). CONCLUSIONS: Our state-wide record-linkage analysis delineated the utilization and clinical performance of the multitude of prenatal screening pathways available to pregnant women. The sensitivity of cfDNA for T21, T18 and T13 was clearly superior to that of CFTS. While there was no statistically significant difference in the residual risk of any major chromosomal abnormality after a low-risk CFTS or cfDNA result, there were fewer live infants diagnosed with a major chromosomal abnormality in the cfDNA cohort. These data provide valuable population-based evidence to inform practice recommendations and health policies. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

The predictive value of cervical shear wave elastography in the outcome of labor induction.

INTRODUCTION: Bishop score, the traditional method to assess cervical condition, is not a promising predictive tool of the outcome of labor induction. As an objective assessment tool, many cervical ultrasound measurements have been proposed to represent the individual components of the Bishop score, but none of them can measure the cervical stiffness. Cervical shear wave elastography is a novel tool to assess the cervical stiffness quantitatively. MATERIAL AND METHODS: A total of 475 women who required labor induction were studied prospectively. Prior to routine digital assessment of the Bishop score, transvaginal sonographic measurement of cervical length, posterior cervical angle, angle of progression and shear wave elastography was performed. Shear wave elastography measurement was made at the inner, middle and outer regions of the cervix to assess homogeneity. Association of labor induction outcomes including the overall cesarean section and subgroups of cesarean section for failure to enter active phase, with cervical sonographic parameters and the Bishop score, were assessed using multivariate regression analyses. The predictive accuracy of the outcomes using models based on ultrasound measurement and the Bishop score was compared using the area under the receiver-operating characteristics curves. RESULTS: Among 475 women, 82 (17.3%) required cesarean section. Shear wave elasticity was significantly higher in the inner cervical region than in other regions, indicating a greater stiffness (P < 0.001). Both inner cervical shear wave elasticity and cervical length were independent predictors of overall cesarean section (respective adjusted odds ratio [95% CI] 1.338 [1.001-1.598] and 1.717 [1.077-1.663]) and cesarean section for failure to enter active phase (respective adjusted odds ratio [95% CI] 1.689 [1.234-2.311] and 2.556 [1.462-4.467]), after adjusting for other covariates. Outcome prediction models using inner cervical shear wave elasticity and cervical length, had increased area under curve compared with models using the Bishop score (0.888 vs 0.819, P = 0.009). CONCLUSIONS: The cervix is not a homogenous structure, with the inner cervix having the highest stiffness, which is an independent predictor of overall cesarean section, and specifically for those indicated because of failure to enter active phase. Models based on shear wave elastography and cervical length had higher predictive accuracy than models based on the Bishop score.

Imperatorin ameliorates learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling in prenatally-stressed female offspring.

Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear. We investigated the protective effect of IMP treatment after PS on learning and memory deficits in female offspring at postnatal 60 days. After treating prenatally-stressed offspring with IMP (15 and 30 mg/kg) for 28 days, we found that IMP increased body weight and ameliorated spatial learning and memory and working memory deficits in female offspring rats. Meanwhile, hippocampal Glu and serum corticosterone levels in prenatally-stressed offspring were significantly decreased after IMP administration. Additionally, IMP treatment significantly increased BDNF, TrkB, CaMKII, and CREB mRNA expression in the hippocampus of offspring rats. Furthermore, PS-mediated induction of RKIP protein and mRNA expression and glucocorticoid receptor protein expression in the hippocampus of offspring rats were significantly decreased by IMP treatment, and the protein expression of BDNF and TrkB and relative levels of p-EKR/ERK, p-CaMKIIα/CaMKIIα, and p-CREB/CREB were remarkably increased after IMP treatment. Taken together, IMP can ameliorate PS-induced learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathway and hypothalamic-pituitary-adrenal axis.

[Differences in spatial distribution of medicinal plant resources in Yinshan region of Inner Mongolia].

Yinshan Mountains stands on the southern edge of the Inner Mongolia Plateau, which stretches 1 200 km from east to west and 50 to 100 km from north to south. The rich and varied topographic environment of the Yinshan Mountains has created a variety of vegetation floras, which also makes the species of medicinal plant resources in this area unevenly distributed. Therefore, studying the spatial distribution difference of medicinal plant resources among various banners, counties, and districts in the Yinshan area is of great significance to formulate the protection policy and promote the industry development of medicinal plant. This study is based on the fourth national survey of traditional Chinese medicine resources in Inner Mongolia, regarding the results of the third national survey of traditional Chinese medicine resources. The species of medicinal plant resources in the Yinshan area around 31 banners, counties and districts were counted in detail. Then, using exploratory spatial data analysis(ESDA), trend surface analysis, spatial autocorrelation, geographical detector and other geostatistical analysis methods to analyze the differences in the spatial distribution of medicinal plant resources of the Yinshan area in Inner Mongolia. After discussing and analyzing the experimental results to account for the reasons for the overall trend of change and the degree of aggregation, the author further put forward relevant constructive suggestions. The results show that the areas with the most abundant and concentrated distribution of medicinal plant resources in the Yinshan area are located in Guyang county, Shiguai District of Baotou city, Tutou right banner, and Tuoketuo county; the higher richness and concentrated distribution of medicinal plant resources is in Wulate front banner, Wulate middle banner, Wulate back banner; areas with relatively low abundance and concentrated distribution of medicinal plant resources located in Qingshan district of Baotou city, Saihan district and Yuquan district of Hohhot city; areas with the lowest abundance and concentrated distribution of medicinal plant resources are located in Xincheng district and Huimin district of Hohhot city. It can be concluded that the horizontal distribution difference of multiple ecological factors, the special wetland environment of the river, the vertical difference of elevation, the farmland and other factors have an important influence on the richness of the medicinal plant resources species.

Correction to: In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

In the original version of this article, the Publisher incorrectly listed the affiliation of the author, G.M. Leung. The correct affiliation for this author should be: School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Population-based trends in invasive prenatal diagnosis for ultrasound-based indications: two decades of change from 1994 to 2016.

OBJECTIVE: To assess trends in ultrasound-indicated prenatal diagnostic testing performed over the past two decades in the Australian state of Victoria, in the context of rapidly changing practices in aneuploidy screening and chromosome analysis. METHODS: This was a retrospective analysis of all ultrasound-indicated prenatal diagnostic testing (amniocentesis and chorionic villus sampling) performed in the state of Victoria between 1994 and 2016. Ultrasound indications for testing included: fetal structural abnormality, fetal death, fetal growth restriction, abnormal amniotic fluid volume, genetic 'soft marker' and unspecified ultrasound abnormality. Maternal age, indication for testing, type of diagnostic procedure, gestational age, type of chromosome analysis (G-banded karyotyping or chromosomal microarray (CMA)) and test results were obtained. Diagnostic yield (i.e. percentage of tests yielding a major abnormality) was analyzed by year, maternal age and gestational age. Statistical analysis was performed using the χ2 tests for trend or difference in proportions, as appropriate. RESULTS: During the 23-year study period, 1 533 317 births were recorded and 16 152 diagnostic procedures were performed for the primary indication of ultrasound abnormality. In recent years, ultrasound abnormality became the most common indication for prenatal invasive testing (29.4% of diagnostic tests between 2013 and 2016) due to a steep decline in testing for other indications such as positive result on combined first-trimester screening or advanced maternal age alone. In 2016, over 95% of ultrasound-indicated procedures were performed with CMA; among these, pathogenic copy number variant (CNV) was the most common (3.5%) abnormality detected, followed by trisomy 21 (2.8%). The diagnostic yield of ultrasound-indicated tests performed < 16 weeks was significantly higher than that of tests performed after 20 weeks (31.5% vs 9.0%). CONCLUSIONS: Ultrasound-indicated invasive testing is contributing to prenatal diagnosis in new ways in the genomic era. A pathogenic CNV is now the most likely diagnosis after ultrasound-indicated testing, rather than trisomy 21 or other whole-chromosome aneuploidy. Despite steady improvements in first-trimester screening for aneuploidy, the diagnostic yield of ultrasound-indicated tests > 20 weeks has remained stable due to increased utilization of CMA. Procedures performed for structural abnormalities < 16 weeks continue to have the highest diagnostic yield, supporting the benefits of early fetal structural assessment at 11-13 weeks. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Cerebral-placental-uterine ratio as novel predictor of late fetal growth restriction: prospective cohort study.

OBJECTIVE: Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR. METHODS: This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, individually and in combination, for prediction of birth weight < 10th , < 5th and < 3rd centiles. Doppler values were converted into centiles or multiples of the median (MoM) for gestational age. The sensitivities, positive and negative predictive values and odds ratios (OR) of the Doppler parameters for these birth weights at ∼ 90% specificity were assessed. Additionally, the correlations between Doppler measurements and other measures of placental insufficiency, namely fetal growth velocity and neonatal body fat measures, were analyzed. RESULTS: The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) divided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At ∼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10th centile, 68% for < 5th centile and 89% for < 3rd centile. The respective sensitivities of low CPR MoM were 26%, 37% and 44% and those of high UtA-PI MoM were 34%, 47% and 67%. Low CPUR MoM was associated with birth weight < 10th centile with an OR of 9.1, < 5th centile with an OR of 17.3 and < 3rd centile with an OR of 57.0 (P < 0.0001 for all). CPUR MoM was also correlated most strongly with fetal growth velocity and neonatal body fat measures, as compared with CPR MoM or UtA-PI MoM alone. CONCLUSIONS: In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Elevated Plasma D-Dimer in Adult Community-Acquired Pneumonia Patients is Associated with an Increased Inflammatory Reaction and Lower Survival.

BACKGROUND: Community-acquired pneumonia (CAP) is a common infectious disease. Inflammatory reaction and prognosis assessment in adult CAP patients are useful for CAP site of care decisions. Most CAP patients were diagnosed in an out-patient or emergency department, so a simple, cheap and rapidly available measurement to assess inflammatory reaction and prognosis has the prospect of broad application. The aim of this study was to investigate the usefulness of plasma D-Dimer in assessment of inflammatory reaction and prognosis in adult CAP patients. METHODS: A retrospective study was conducted. All adult patients with a primary diagnosis of CAP were included and were evaluated by peripheral plasma D-Dimer test. All of the measurement data were analyzed with paired t-test and the enumeration data were analyzed with χ2 test. Correlative factor analysis was performed between D-Dimer levels and serum inflammatory markers (WBC, hs-CRP, PCT) and prognostic indexes (ICU admission and 30-day mortality). Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of D-Dimer in predicting ICU admission and/or 30-day mortality. RESULTS: One hundred fifty patients were included. Compared with non-D-Dimer elevated group, serum inflammatory markers (WBC, hs-CRP, PCT) and prognostic indexes (ICU admission and 30-day mortality) were elevated in the D-Dimer elevated group (p < 0.05). D-Dimer had positive correlation with serum inflammatory markers (WBC, hs-CRP, PCT), the rates of ICU admission and 30-day mortality, and scores of CURB-65. The AUC of ROC curve of D-Dimer was 0.880 (95% CI 0.823 to 0.936), the sensitivity was 80.4% and specificity was 79.8%, D-Dimer levels are superior to hs-CRP and PCT in predicting 30-day mortality and/or ICU admission according to AUCs of the ROC curves. CONCLUSIONS: Elevated plasma D-Dimer in adult CAP patients is associated with an increased inflammatory reaction and ICU admission and 30-day mortality. It can be a simple, cheap, and rapidly available measurement to assess inflammatory reaction and prognosis in adult CAP patients.

Elevated Red Blood Cell Distribution Width Combined White Blood Cell in Peripheral Blood Routine Have a Better Sensitivity than CURB-65 Scores in Predicting ICU Admission and Mortality in Adult Community-Acquired Pneumonia Patients.

Background: Scoring systems including CURB-65 and Pneumonia Severity Index (PSI) and novel or traditional biomarkers including procalcitonin (PCT) and c-reactive protein (CRP) are very significant for understanding the severity and prognosis in community-acquired pneumonia (CAP) patients, while prognostic items are useful for CAP prognostication and point-of-care decisions. The aim of this study was to investigate the usefulness of peripheral blood routine items in predicting ICU admission and 30-day mortality in CAP patients.

Methods: A retrospective study was conducted. All adult patients with a primary diagnosis of CAP were included and peripheral blood routine tests were evaluated. Univariate analysis and multivariate logistic regression analysis were used to explore association of risk factors with 30-day mortality among CAP patients. Receiver operating characteristic curves (ROC) were used to evaluate the sensitivity and specificity of peripheral blood routine items and compared with CURB-65 scores in predicting ICU admission and/or 30-day mortality.

Results: One hundred fifty patients were included and compared with non-ICU admission patients. There was a statistically significant difference in age, co-existing illness, RDW, WBC, and CURB-65 scores ranking in ICU admission patients (p < 0.05). In multivariate logistic regression analysis, we found RDW, WBC, and CURB-65 ≥ 3 scores increased the risk of 30-day mortality by 4.01, 1.65, and 3.43 times, respectively. The area under the curve (AUC) of ROC curves of RDW combined with WBC and CURB-65 was 0.786 (95% CI 0.701 to 0.876) and 0.836 (95% CI 0.764 to 0.908), respectively and the sensitivity was 84.0% and 60.0%, respectively, and the specificity 66.7% and 93.7%, respectively.

Conclusions: Elevated RDW and WBC increased mortality in adult CAP patients, RDW combined with WBC had a better sensitivity than CURB-65 scores in predicting ICU admission and/or mortality in CAP patients.

New-onset diabetes mellitus among patients with glomerular diseases.

BACKGROUND: Glomerulonephritis commonly causes kidney failure. Immunosuppressant treatment may be diabetogenic, but data on hyperglycaemia in glomerulonephritis treated with usual clinical care are scant. AIM: To assess the epidemiology, risk factors and outcomes for new-onset diabetes among patients with glomerular disease (NODAG). METHODS: A single-centre retrospective cohort of nondiabetic adults diagnosed with glomerulonephritis between January 2011 and July 2015. Clinical, laboratory and pharmacotherapy data were retrieved from electronic medical records. Using modified American Diabetes Association criteria, the primary outcome of NODAG was present if fasting venous glucose was ≥7 mmol/L for at least two readings, HbA1c was ≥6.5% or if patient required antidiabetic medications. Secondary outcomes were end-stage renal disease, cardiovascular disease and death. RESULTS: NODAG occurred in 48 patients (10.7%); 22 required antidiabetic medication at median 6.2 (interquartile range 1.7, 20.0) months after glomerulonephritis diagnosis. Patients with NODAG had higher prebiopsy fasting glucose, greater proteinuria and lower fasting high-density lipoprotein cholesterol levels. Methylprednisolone and cyclophosphamide were more commonly used among patients with NODAG. In multivariate logistic regression, greater proteinuria (odds ratio 1.08 (95% confidence interval 1.01, 1.16), P = 0.02) and methylprednisolone use (odds ratio 4.02 (95% confidence interval 1.76, 9.18), P = 0.001) were significantly associated with NODAG, independent of the triglyceride/high-density lipoprotein cholesterol ratio as a surrogate measure of insulin resistance. Median follow up was 39.6 (26.9, 57.2) months. Secondary outcomes were not significantly different in patients with and without NODAG. CONCLUSION: Proteinuria and methylprednisolone were associated with incident diabetes among patients with glomerular disease treated with usual care. At-risk patients should be appropriately counselled and monitored for hyperglycaemia.

The hidden patient: chronic physical morbidity, psychological distress, and quality of life in caregivers of older adults.

AIM: Increasing demands for care provision to older adults require good physical and mental health among caregivers. Few studies have examined the health status and correlates of quality of life among caregivers of older adults. The present study therefore sought to examine the prevalence of chronic physical conditions, psychological distress, and correlates of physical and mental quality of life among caregivers of older adults (≥60 years) in Singapore. METHODS: Participants were 285 informal caregivers who were providing care to an older relative. Participants were recruited at the Institute of Mental Health, Singapore, and they completed self-report measures on chronic physical morbidity, psychological distress, and physical and mental quality of life. Multiple regression models were constructed to examine correlates of physical and mental quality of life. RESULTS: More than half of the caregivers had at least one chronic physical condition (58.6%) and psychological distress (52.6%). Chronic physical morbidity, psychological distress, and secondary education status were associated with lower physical quality of life. Psychological distress, younger age, primary education status, and more time spent caregiving were associated with lower mental quality of life. CONCLUSION: Poor physical and mental health among caregivers may impair their ability to provide adequate care to older adults with progressive medical needs. It is important for medical practitioners not to neglect the physical and mental health of caregivers through continued assessment of chronic physical morbidity, psychological distress, and quality of life.

In utero exposure to gestational diabetes and adiposity: does breastfeeding make a difference?

BACKGROUND/OBJECTIVES: Short-term breastfeeding from mothers with gestational diabetes (GDM) may programme metabolism and increase offspring diabetes risk. We examined the association of in utero GDM exposure with adiposity from infancy to adolescence, and whether any association was modified by breastfeeding during early infancy. METHODS: In the prospective Chinese birth cohort "Children of 1997" (n = 7342, 88% follow-up rate), generalised estimate equations with multiple imputation were used to assess associations of in utero GDM exposure with age- and sex-specific body mass index (BMI) z-score during infancy (3 and 9 months), childhood (2- < 8 years) and adolescence (8-16 years), adjusted for sex, parity, maternal age, birth place, preeclampisa, smoking, and family socio-economic position. We also tested whether the associations differed by mode of infant feeding (always formula-fed, mixed, always breastfed) during the first three months of life. RESULTS: In utero GDM exposure (7.5%) was associated with a lower BMI z-score during infancy (-0.13, 95% confidence interval (CI) -0.22, -0.05) but higher BMI z-scores during childhood (0.14, 95% CI 0.03, 0.25) and adolescence (0.25 95% CI 0.11, 0.38). Breastfeeding for the first three months did not modify the association of in utero GDM status with subsequent BMI (all p values for interaction >0.4). CONCLUSIONS: In utero GDM exposure was associated with greater adiposity during childhood and adolescence. Breastfeeding in early infancy from mothers with GDM was not associated with greater adiposity in children and thus should still be encouraged.

The effects of a CCR3 inhibitor, AXP1275, on allergen-induced airway responses in adults with mild-to-moderate atopic asthma.

BACKGROUND: CCR3 is the cognate receptor for major human eosinophil chemoattractants from the eotaxin family of proteins that are elevated in asthma and correlate with disease severity. OBJECTIVE: This proof-of-mechanism study examined the effect of AXP1275, an oral, small-molecule inhibitor of CCR3, on airway responses to inhaled allergen challenge. METHODS: Twenty-one subjects with mild atopic asthma and documented early and late asthmatic responses to an inhaled aeroallergen completed a randomized double-blind cross-over study to compare early and late allergen-induced asthmatic responses, methacholine PC20 , blood and sputum eosinophils and exhaled nitric oxide after 2 weeks of treatment with once-daily doses of AXP1275 (50 mg) or placebo. RESULTS: There was a significant increase in methacholine PC20 after 12 days of AXP1275 treatment compared to placebo (increase of 0.92 doubling doses versus 0.17 doubling doses, P = .01), but this protection was lost post-allergen challenge. There was no effect of AXP1275 on allergen-induced late asthmatic responses, or eosinophils in blood and sputum. The early asthmatic response and exhaled nitric oxide levels were slightly lower with AXP1275, but this did not reach statistical significance. The number of subjects who experienced treatment-emergent adverse events while receiving AXP1275 was comparable placebo. CONCLUSIONS & CLINICAL RELEVANCE: AXP1275 50 mg administered daily was safe and well tolerated, and there was no difference in the type, severity or frequency of treatment-emergent adverse events in subjects while receiving AXP1275 compared to placebo. AXP1275 increased the methacholine PC20 ; however, the low and variable exposure to APX1275 over a short treatment period may have contributed to poor efficacy on other outcomes.